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Open AccessReview

Functional Analogues of Salicylic Acid and Their Use in Crop Protection

by Lydia Faize 1 and Mohamed Faize 2,*
Group of Fruit Tree Biotechnology, Department of Plant Breeding, CEBAS-CSIC, 30100 Murcia, Spain
Laboratory of Plant Biotechnology and Ecosystem Valorisation, Faculty of Sciences, University Chouaib Doukkali, El Jadida 24000, Morocco
Author to whom correspondence should be addressed.
Agronomy 2018, 8(1), 5;
Received: 9 December 2017 / Revised: 30 December 2017 / Accepted: 4 January 2018 / Published: 9 January 2018
(This article belongs to the Special Issue Salicylic Acid in Plant Stress Responses)


Functional analogues of salicylic acid are able to activate plant defense responses and provide attractive alternatives to conventional biocidal agrochemicals. However, there are many problems that growers must consider during their use in crop protection, including incomplete disease reduction and the fitness cost for plants. High-throughput screening methods of chemical libraries allowed the identification of new compounds that do not affect plant growth, and whose mechanisms of action are based on priming of plant defenses, rather than on their direct activation. Some of these new compounds may also contribute to the discovery of unknown components of the plant immune system.
Keywords: salicylic acid; functional analogues; priming; crop protection salicylic acid; functional analogues; priming; crop protection

1. Introduction

Increasing demand for environmentally-friendly alternatives to traditional pesticides is an impetus for designing new biological strategies for crop protection. Stimulating the natural plant immunity through induced resistance is among those strategies [1]. Upon infection, the plants are able to fight against pathogen attacks by activating their immune mechanisms that are initiated after the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors. This activated immunity is called PAMP-triggered immunity (PTI) [2]. However, some pathogens are able to suppress PTI via effector proteins. In this case, plants are able to defend themselves via effector triggered immunity (ETI) involving resistance genes products (R) and is usually associated with hypersensitive responses (HR) that are characterized by rapid programmed cell death at the penetration site [3]. Both responses involve accumulation of reactive oxygen species (ROS) in infected tissues, followed by the activation of mitogen activated protein kinases (MAPKs) and increase in the expression of defense-related genes, including pathogenesis that are related (PR) genes and salicylic acid (SA) accumulation [4,5]. Subsequently an immune response, called systemic acquired resistance (SAR) is induced in distal non-inoculated parts of the plant against broad spectrum of pathogen [6]. Other phytohormones including jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA) are also involved in regulation of induced plant immunity. While SA induces defenses by and against biotrophic pathogens JA mediate defenses by and against necrotrophic pathogens and herbivorous insects. The cross-talk among these different signaling pathways leads to the fine-tune of the plant defense responses against specific aggressors [7,8].
SAR is considered as the most agronomically relevant type of plant immunity [6] and can also be triggered by signal molecules that are involved in plant resistance to pathogens, including SA and a wide range of synthetic compounds. Among these compounds functional analogues of SA are able to activate plant defense responses and provide attractive alternatives to conventional biocidal agrochemicals. They are able to mimic a subset of known SA functions by directly interfering with its receptors or by triggering transcriptional and physiological responses that are related to those induced by SA without directly interfering with SA targets [9]. Although they generally do not possess antimicrobial activity in vitro and can activate resistance against broad spectra of pathogens by inducing SAR genes that are triggered by biological or SA inducers they are many problems that growers must consider during their use in crop protection, including incomplete disease reduction and the fitness cost for plants [10]. High-throughput screening methods of chemical libraries allowed the identification of new compounds that do not affect plant growth, and whose mechanisms of action are based on priming of plant defenses upon pathogen infection rather on their direct activation [11,12,13].
After a brief description of the mode of action of SA in plant defense we will review the most important groups of functional analogues of SA with their use as plant protective agents. Particular attention will also be given to the methods used for screening of chemical libraries to obtain new compounds. These new agrochemicals will not only provide resistance against a broader spectrum of plant pathogens, but may also contribute to the identification of novel pathway components of SAR.

2. Mode of Action of SA in Plant Defense

SA is one of several plant hormones acting as an endogenous signal to trigger plant immunity responses and to allow the establishment of disease resistance. The SA pathway is primarily induced by and against biotrophic pathogens and is often hindered by various feedback loops and cross-talk with other phytohormones that modulate the SA signal, including jasmonic acid (JA) and ethylene (ET) [7,8]. Exogenous application of SA can induce ROS production, PR genes expression, and disease resistance against a wide range of biotrophic and hemibiotrophic fungal, bacterial, viral, as well as phloem-feeding insects. For instance, exogenous application of SA confers resistance against tobacco mosaic virus (TMV) [7], cauliflower mosaic virus [14] and turnip crinkle virus in Arabidopsis thaliana [15]. Treatment of Nicotiana benthamiana with SA results in reduced grown gall symptoms caused by Agrobacterium tumefaciens [16]. It is also effective in controlling fire blight disease that is caused by the bacterium Erwinia amylovora in pear [17]. Regarding phytopathogenic fungi SA induces resistance in A. thaliana against the powdery mildew pathogen Erysiphe orontii [18] and the downy mildew pathogen Hyaloperonospora parasitica [19]. Its efficacy was also probed in tobacco against the powdery mildew pathogen Oidium sp. [20], in tomato against leaf blight caused by Alternaria solani [21], and in cherry fruits against fruit rot caused by Monilia fructicola [22].
SA is synthesized via two distinct and compartmentalized pathways [23]. It is produced through the phenylalanine pathway by decarboxylation of trans-cinnamic acid to benzoic acid, followed by hydroxylation to SA. Alternatively, cinnamic acid may be hydroxylated to o-coumaric acid and then decarboxylated to SA [24]. In the isochorismate pathway, SA synthesis involves isochorismate synthase (ICS), which converts chorismate to isochorismate [25]. The expression of ICS1 is positively regulated by several transcription factors (TFs), including calmodulin-binding protein 60 g (CBP60g). PAMP recognition generates calcium influx in the cytosol which is transduced to calmodulin-binding protein CBP60g and WRKY28 triggering activation of isochorismate synthase and SA biosynthesis [26]. Recently, a third pathway involving cyanogenic glycosides, such as prunasin and mandelonitrile have been also recognized to be involved in SA synthesis in peach [27].
In Arabidopsis, the regulation of SA involves two lipase-like proteins acting upstream of SA: EDS1 (for enhanced disease susceptibility) and PAD4 (for phytoalexin deficient) [28]. EDS1 represents an important node that controls SA production to amplify defense signals. It forms a heterodimer with PAD4 that transduces ROS-derived signals leading to enhanced SA production through the accumulation of benzoic acid (BA) and its conversion to SA by benzoic acid 2-hydroxylase (BA2H) [29,30]. SID2 (for SA induction deficient) encodes for an ICS that is involved in the biosynthesis of SA, because a mutation sid2 reduces SA synthesis in A. thaliana and the expression of the PR1 gene [25]. EDS5, also named SID1, is involved in the regulation of SA. It belongs to the multidrug and toxin extrusion (MATE) transporter proteins and is located downstream of PAD4. It is involved in the transport of SA precursors and its expression requires PAD4 [31]. EDS4 is another component that plays a role in SA signaling and in SA-induced SAR [32]. EDS1, PAD4, and EDS4 activate SID2, which produce SA [33].
Upon its synthesis in the chloroplast, SA is transported to the cytosol via EDS5 protein where it will be inactivated via glycosylation or methylation [7,34]. Glycosylation of SA generates SA 2-O-β-d-glucoside (SAG), which is transported to the vacuole and will be hydrolyzed to release free SA after pathogen attack [35]. Methylation of SA generates methyl SA (MeSA), which is supposed to be the mobile SAR signal that travels from the infected to the systemic tissues, where it activates resistance following its reconversion to SA. Following pathogen infection, SA levels increase dramatically in the inoculated leaves, however it is converted to biologically inactive MeSA by SA methyl transferase (SAMT). Once SA concentration becomes sufficiently high, it binds in the active site of salicylic acid binding protein 2 (SABP2) and prevents its ability to convert MeSA back into SA [35]. Methylation of SA causes a change in the potential redox of the chloroplast cell wall facilitating its translocation to cytoplasm of the distal, uninfected tissue. Since SA levels in the distal tissue are too low to inhibit SABP2, the transported MeSA is converted to active SA, which then induces systemic defense responses [35]. Other mobile signaling molecules includes a non-proteinaceous amino acid pipecolic acid (Pip) [36] and azelaic acid; a 9-carbon dicarobxylic acid, which has been reported to be limited to vascular sap in A. thaliana inoculated with P. syringae [37]. The diterpenoid Dehydroabietinal (DA) was also shown to be translocated far from treated tissues in Arabidopsis, tobacco, and tomato, where it enhances the accumulation of SA and the expression of PR1 gene [38]. Other mechanisms that are preventing over-accumulation of SA and generation of the mobile signal of SAR involve its conversion to 2,3-dihydroxybenzoic acid (2,3-DHBA) by SA 3-hydroxylase (S3H; also termed DLOL1) and the formation of SA-amino acid conjugates such as salicyloyl-aspartate (SA-Asp) synthesized by a member of the GH3 acyl adenylase family of early auxin-responsive genes named GH3.5 [39].
Defense signaling downstream of SA is regulated via NPR1 and NPR3/4 homeostasis in a concentration dependent manner. This determines the levels and selective activation of defense responses, which should be switched on during pathogen infection [40]. NPR1 is a considered as master regulator of the SA-mediated defense genes. It binds to SA through two Cysteine residues 521 and 529 [41]. NPR1 is located in the cytoplasm, but pathogen induced SA accumulation activates its expression, and stimulates its translocation into the nucleus where it interacts with TGA transcription factors binding to the so called as-1 (activation sequence-1) like element of the PR1 promoter [42]. In the absence of infection NPR1 is continuously cleared from the nucleus via proteasome-mediated degradation, a process mediated by NPR3 and NPR4, which are adaptors for Cullin 3 ubiquitin E3 ligase [40]. NPR4 maintains low NPR1 levels, however after infection, at higher concentration SA binds to NPR4 and disrupts the NPR1–NPR4 interaction, allowing for NPR1 to accumulate and defense signaling to occur. In cells containing sufficiently high SA levels, NPR3 binds NPR1; this promotes NPR1 turnover, which optimizes defense activation and resets NPR1 levels [43].

3. Functional Analogues of SA

Although SA is a potent inducer of plant resistance its rapid glycosylation often leads to its reduced efficacy. In addition, its phytotoxicity has prevented its development as plant protection compounds [44]. For this reason, several functional analogues of SA with stable and effective activities have been explored so far. Most of the synthetic compounds targeting SA pathways demonstrated their effectiveness as plant defense activators in the field of crop protection, while others constitute valuable tools for dissecting components of the plant immune system. Apart from β-aminobutyric acid (BABA), we have classified these compounds according to their structures: (I) salicylate and benzoate compounds; (II) nicotinic acid derivatives; (III) pyrazole, thiazole, and thiadiazole heterocycles; (IV) pyrimidin derivatives; and, (V) neonicotinoid compounds.

3.1. β-Aminobutyric Acid

BABA is a non-protein amino acid that is known to induce resistance against many plant pathogens in various systems, by inducing both SA-dependent and SA-independent plant defense mechanisms [45] (Table 1). BABA has been shown to protect Arabidopsis against H. parasitica and Botrytis cinerea [46]. In lettuce, application of BABA prior to inoculation with the fungal pathogen Bremia lactucae prevented pathogen development without the involvement of SA [47]. BABA also provided significant control of the late blight pathogen Phytophthora infestans on tomato [48]. BABA protected Brassica napus against the fungal pathogen Leptosphaeria maculans by activating SA synthesis and the expression of PR1, but was also found to act as an antifungal agent [49]. Field experiments revealed that BABA was able to reduce severity of Plasmopara viticola on grapevine [50]. BABA also provided significant control of potato late blight in the field when used alone or in combination of the standard fungicide [51]. In potato, it was able to induce HR-like lesions surrounded by callose and the production of H2O2, as well as the enhancement of phenolic content and activation of PR1 [52]. To elucidate in depth molecular mechanisms of BABA-induced resistance against potato late blight, Bengtsson et al., developed an original approach based on a transcript analysis in combination with quantitative proteomic analysis of the apoplast secretome. They showed that several processes that were related to plant hormones and amino-acid metabolisms were affected, in addition to genes that are involved in sterol biosynthesis that were down regulated and those involved in phytoalexin biosynthesis that were up-regulated [53].

3.2. Salicylate and Benzoate Derivatives

Several derivatives of SA were tested as SAR activators in the greenhouse [54] (Table 2). 3,5-dichlorosalicylic acid, 4-chlorosalicylic acid, and 5-chlorosalicylic acid, induced PR1 gene expression and enhanced disease resistance to TMV infection in tobacco [55]. Screening experiments revealed that the monosubstituted salicylates; 3-chlorosalicylic acid, 3-fluorosalicylic acid and 5-fluorosalicylic acid caused increased PR1 induction than SA and that substitution on position 3- or 5 enhanced further PR1 activity [56]. Recently, Cui et al. [57] synthetized a series of salicylic glycoconjugate containing hydrazine and hydrazone moieties and found that the salicylate hydrazine derivative was able to enhance cucumber resistance against several phytopathogenic fungi including Colletotrichum orbiculare, Fusarium oxysporum, Ralstonia solani and Phytophthora capsici. Although it is structurally related to SA it did not mimic the mode of action of SA as it activated the JA rather than SA pathway [57].
Aminobenzoic derivatives were also reported to induce SAR (Table 2). For instance, Para-aminobenzoic acid (PABA), which is a cyclic amino acid that belongs to the vitamin B group, was able to induce SAR in pepper against cucumber mosaic virus (CMV) and Xanthomonas axonopodis pv. vesicatoria through SA pathway [58]. The substituted benzoates, 3-chlorobenzoic acid and 3,5-dichlorobenzoic acid induced basal defense against H. parasitica in A. thaliana [54]. The compound 3,5-dichlorobenzoic acid, known as 3,5-dichloroanthranilic acid (DCA), was reported to efficiently trigger resistance of A. thaliana against H. parasitica and P. syringae. It up-regulates transcript levels of various known SA-responsive defense-related genes, such as PR1, WRKY70, and CaBP22. DCA does not require accumulation of SA and triggered immune responses that are largely independent from NPR1. However, it partially targets a WRKY70-dependent branch of the defense signaling pathway [54]. Microarray analyses revealed that DCA triggers the expression of 202 genes that are commonly regulated by other functional analogues such as INA, and BTH, but also the expression of unique genes [59].

3.3. Nicotinic Acid Derivatives: 2,6-dichloro-isonicotinic Acid (INA) and N-cyanomethyl-2-chloro isonicotinic Acid (NCI)

INA is very effective in protecting various crops against a wide range of pathogens (Table 3). This includes tobacco against TMV and cucumber against Colletotrichum lagenariunm [60] Cercospora nicotianae, Peronospora tabacina, Phytophthora parasitica var nicotianae, and against P. syringae pv. tabaci [61]. Although, INA has not been commercialized because of its high phytotoxicity it is considered as useful tools to study mechanisms of induced resistance. INA is considered as a functional SA analogue that acts downstream of SA because it does not trigger any changes of SA content and it induces SAR in salicylate hydroxylase (NahG) transgenic plants [62,63]. Like SA, INA is able to inhibit catalase and ascorbate peroxidase (APX) activity and to induce ROS accumulation [64]. INA mediates its defense-related effects upon interaction with NPR1-related proteins, which control several TGA transcription factors. INA seems to be a true SA agonist. It is able to promote NPR1–NPR3 interactions, and to reduce the binding affinity of SA to NPR3 and NPR4 by competing with SA [40].
A second isonicotinic acid derivative, named N-cyanomethyl-2-chloro isonicotinic acid (NCI), was identified by Nihon Nohyaku Co., Ltd. (Tokyo, Japan) as a potent defense inducer against rice blight under field conditions [65] (Table 3). It does not show any antifungal activity in vitro against Magnatoporthe oryzae, and its activity is long-lasting. In tobacco, NCI induces resistance against several pathogens including TMV, Oidium lycopersici and P. syringae pv. tabaci, and enhances the expression of several PR genes. NCI-induced resistance does not require SA accumulation, but NPR1 is involved. Therefore, NCI seems to interfere with defense signaling steps operating between SA and NPR1 [66].

3.4. Pyrazole, Thiazole and Thiadiazole Derivatives

The heterocycles pyrazole, thiazole, and thiadiazole nucleus are prevalent five-membered ring system harboring heteroatom nitrogen, or sulfur. They are considered as the most important components of a wide variety of natural products and medicinal agents. Their derivatives are known for their pharmacological activities, such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular [67,68,69]. Some of them are extensively used as plant defense inducers [70,71].
The pyrazole carboxylic acid derivative, 3-chloro-1-methyl-1H-pyrazole-5-carboxylic acid (CMPA), is a very potent inducer of rice defense against bacterial blast that is caused by X. oryzae pv. oryzae and rice blight without exhibiting any antimicrobial activity in vitro [72,73] (Table 4). The carboxyl group at 5-position plays an important role in the observed activity, but the halogen atom at 3-position enhanced further this activity. In rice, CMPA acts downstream of SA and upstream of NPR1 [66]. In tobacco, it enhances resistance against P. syringae pv. tabaci and Oidium sp [74]. CMPA also induces the expression of several PR encoding genes. However, SA accumulation is not required and may interfere with defense signaling downstream from SA. In A. thaliana CMPA induced resistance through NPR1 [66,74].
The thiazolic compound probenazole (PBZ) (3-allyloxy-1,2-benzisothiazole-1,1-dioxide) is an inducer of plant defense that was developed by Meiji Seika Ltd. (Tokyo, Japan) to control the fungal rice blast disease for more than four decades (Table 4). It was the first commercialized inducer of resistance under the trade name of Oryze mate®. PBZ inhibits hyphal penetration into the host tissue, lesion expansion and sporulation [70]. It provides an excellent blast control lasting for more than two months. Despite of its direct antifungal activity, it is able to dramatically enhance the activity of several enzymes that are involved in plants defenses, such as peroxidase (POX), polyphenol oxidase (PPO), phenyl alanine ammonia lyase (PAL), tyrosine ammonia lyase (TAL), and catechol-O-methyltransferase, as well as transcript accumulation of OsPR1a and PBZ1, a gene belonging to PR10 family that is used as a marker for responses to the synthetic elicitor.
1,2-benzisothiazoline-3-one-1,1-dioxide (BIT) is the derivative metabolite of PBZ. It is well known as saccharin and it also induces resistance against a broad spectrum of pathogens in cereals and leguminous plants. In rice, PBZ-induced defense is independent from the accumulation of SA. PBZ enhances transcripts of SA glucosyltransferase b(OsSGT1), which is involved in the conversion of free SA to SAG [99]. However, in A. thaliana and tobacco, PBZ mimics the effects of SA since it stimulates the expression of PR genes and induces SA accumulation. Since PBZ failed to induce plant defense responses in npr1 mutants or nahG transgenic plants, it seems to interfere only with defense signaling steps upstream from SA accumulation [70,100].
The isotianil compound 3,4-dichloro-2′-cyano-1,2-thiazole-5-carboxanilide is an isothiazole derivative that was developed by Bayer Crop Science (Monheim am Rhei, Germany) and the Japanese company Sumitomo Chemical Co., Ltd (Tokyo, Japan) (Table 4). It is registered under the trade name of Stout® (Sumitomo Chemical Co., Ltd, Tokyo, Japan) to fight against rice blast. Isotianil does not show any direct antimicrobial activity [79,80], but it is able to activate defense responses against a wide range of pathogens in various plants even at very low concentrations. These include rice blight and powdery mildew in wheat, anthracnose, and bacterial leaf spot in cucumber, alternaria leaf spot in chinese cabbage, powdery mildew in Pumpkin, anthracnose in strawberry, and bacterial shot hole in peach [79,81]. In rice, it was reported to enhance the accumulation of defense-related enzymes such as PAL and lipoxygenase (LOX) in rice [79,80]. However, several, isotianil-responsive genes that are involved in SA pathway were identified. These include, NPR1, NPR3, the transcription factors OsWRYK45, OsWRYK62, OsWRYK70, OsWRYK76, as well as genes that are involved in SA catabolism such as OsSGT1 and OsBMST1 leading to the mobile signal MeSA [81].
Several benzothiadiazoles have been found to behave as functional analogues of SA. The Benzo-1,2,3-thiadiazole-7-carbothionic acid-S-methyl ester (BTH) or ASM (for acibenzolar-S-methyl) was the first commercialized thiadiazole derivative. It was registered under the tradename of BION® (Syngenta, Bâle, Switzerland) in Europe in 1989 and Actigard® (Syngenta, Bâle, Switzerland) in the US in 1990 [70]. BTH is effective against a broad spectrum of pathogens, it does not show antimicrobial activity at the concentration used for in planta protection (Table 4). BTH seems to activate SA-dependent signaling pathways by interfering as SA agonists with targets that are located downstream from SA accumulation, and can activate the same PR genes that are induced by SA. However, BTH treatment induces SAR in nahG transgenic plants, which fail to accumulate SA, suggesting that accumulation of SA is not required for BTH-induced SAR [101]. In Arabidopsis, BTH triggers NPR1-dependent SAR [102]. It inhibits catalase and APX, which lead to enhanced H2O2 content and to activation of plant defenses [103]. It was suggested that BTH is converted into acibenzolar by SABP2, which, in turn, activates a disease resistance signaling pathway that is similar to that activated by SA [104]. In addition, a BTH-binding protein kinase (BBPK) isolated from tobacco leaves was reported to regulate NPR1 activity through phosphorylation.
Until now, BTH has been tested in more than 120 pathosystems. These include resistance against E. amylovora, the causal agent of fire blight in apple and pear [82] and against bacterial canker that is caused by Clavibacter michiganensis subsp. michiganensis in tomato [90]. When applied as foliar spray or soil drench, in the field, BTH was able to reduce the lesions produced in grapefruit by Xanthomonas citri and X. axonopodis pv. Citrumelo [83]. BTH enhanced resistance against the bacterial pathogen Pseudomonas syringae pv. maculicola and the fungal pathogen Leptosphaeria maculans in Brassica napus in SA dependent manner [84]. In Japanese pear, BTH reduced scab disease caused by Venturia nashicola and was correlated with enhancement of several lines of plant defenses, including antioxidant defenses, polygalacturonase-inhibiting proteins (PGIP), MAPK, and leucin-rich repeat Receptor like kinase [85,105,106]. BTH enhanced resistance against the anthracnose pathogens Colletotrichum destructivum in cowpea seedlings [86] and Colletotrichum orbiculare in cucumber [107]. BTH also induced resistance in oil seedrape against phoma stem canker caused by Leptosphaera maculans [92]. In tomato, BTH significantly reduced disease incidence and severity against Verticillium dahliae [91] and Botrytis cinerea [108]. It is also relatively effective in controlling various viral diseases in tobacco, such as TMV, tobacco necrosis virus (TNV), and tomato spotted wilt virus (TSWV) [87,88]. Its efficacy was also reported in tomato against cucumber mosaic virus (CMV), and TSWV [89,109]. Because disease reduction conferred by BTH in the field is generally incomplete Du et al. performed several modifications in the 7-ester group of BTH to enhance its efficacy. They found that adding fluorine resulted in compounds with enhanced protective ability against cucumber Erysiphe cichoracearum and Colletotrichum lagenarium [93].
N-(3-Chloro-4-Methylphenyl)-4-Methyl-1,2,3-thiadiazole-5-Carboxamide known as tiadinil (TDL), is the second commercialized thiadiazole derivative. It was registered under the trade name of V-GET® in 2003 by Nihon Nohyaku Co., Ltd. (Tokyo, Japan) (Table 4). It confers rice blight resistance without exhibiting any antimicrobial activity [80,110]. Its metabolite, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid (SV-03), seems to be responsible for SAR activation [94]. TDL also protects tea plants in the field against the fungal diseases that are caused by Colletotrichum theaesinensis and Pestalotiopsis longiseta [95]. In tobacco, TDL and SV-03 induce resistance against TMV, the wildfire bacterial pathogen, and the powdery mildew. TDL acts in similar way to BTH by activating signals downstream of SA [66,94]. They failed to induce accumulation of SA in tobacco or to activate defense genes in Arabidopsis npr1 mutants. However, they enhanced resistance against TMV and P. syringae pv. tabaci, as well as PR gene expression in NahG transgenic tobacco plants.
Recently, several derivatives of the isomer 1,3,4-thiadiazole were synthetized and tested as SAR inducers against Verticillium wilt and crown gall diseases (Table 4). The derivative 2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole was reported to enhance tomato disease resistance and to activate plant defense mediated by ROS [96]. Furthermore, several metallic complexes harboring Ni or Cu as transient metal were synthetized and proved to activate SAR against Verticillium wilt. Their protection ability was associated with modulation of ROS accumulation and priming the activity of several plant defense-related enzymes, including peroxidase and polyphenol oxidase [96,97,98]. However, further experiments are needed to determine whether they act in similar way to BTH or not.

3.5. Pyrimidine Derivatives

A new plant defense activator, 5-(cyclopropylmethyl)-6-methyl-2-(2-pyridyl)pyrimidin-4-ol, named PPA (pyrimidin-type plant activator), belonging to the pyridyl-pyrimidine derivative family was reported to enhance the expression of genes related to ROS, defenses, and SA in A. thaliana. PPA was able to reduce disease symptoms that were caused by P. syringae pv. maculicola and to enhance plant defenses against pathogen invasion through the plant redox system [111]. Recently, Narusaka and Narusaka identified several thienopyrimidine-type compounds that enhance disease resistance against Colletotrichum higginsianum and P. syringae pv. maculicola in A. thaliana. However, they induce the expression of both PR1 and PDF1.2 [112].

3.6. Neonicotinoid Compounds

The neonicotinoid imidacloprid (IMI) and clothianidin (CLO) basically used to control crop pests have also been reported to induce plant defenses that are associated with SA and to inhibit the growth of powdery mildew in A. thaliana [113]. However, their effect was mainly due to their respective metabolites; 6-chloropyridinyl-3-carboxylic acid and 2-chlorothiazolyl-5-carboxylic acid. While CLO enhanced SA accumulation through the upregulation of ICS transcripts, and activated the expression of PR1 gene, IMI does not induce endogenous synthesis of SA, but it is further transformed to 6-chloro-2-hydroxypyridinyl-3-carboxylic acid, a potent inducer of PR1 and inhibitor of SA-sensitive enzymes [113]. In addition, IMI activates PR2 gene expression and induces high and long-lasting levels of resistance against the bacterial canker of Citrus X. citri [114].

4. Limitations of the Use of Functional Analogues of SA: Towards a New Generation of Compounds

4.1. Allocation Fitness Cost

Limitations of the use of SA analogues in the field include their transient effect and their limited disease spectrum and target crops. However, the major drawback is related to their phytotoxicity when applied at higher doses. These effects are likely to be caused by the strong induction of defense responses, which is associated with growth inhibition [115]. Resources used in the primary metabolism are deviated and used for synthesis of defensive compounds, resulting in plant growth inhibition, a phenomenon known as ‘allocation fitness cost’ or ‘trade-off’ [116,117,118,119]. This notion comes from the use of Arabidopsis mutants and the observation that higher doses of SA or its functional analogues are often associated with direct inhibition of plant growth and seed production [10,120,121]. While mutants of Arabidopsis expressing constitutively PR genes were dwarfed and severely affected in seed production [11,122], those that are affected in SA accumulation, such as NahG or ICS1, showed enhanced growth and seed production [121,123]. High concentrations of BTH in sunflower resulted in light chlorosis and reductions in fresh weight [124]. Repetitive application of BTH also provoked yield reduction in pepper [124]. The beneficial effects of SA-regulated defenses were particularly apparent under low-nutrient conditions [125], which supports the theory of allocation costs as a driver of the evolution of inducible defenses. BTH-treated wheat exhibited reduced growth and decreased seed production, mainly under deficiency of nitrogen [120]. Since reduced vigor observed after treatment with BTH was alleviated in npr1 mutants, it was suggested that NPR1 plays a pivotal role in inhibiting plant growth when SA-dependent resistance mechanisms are activated [10]. In addition to SA pathway, several interconnecting signals interacting synergistically or antagonistically, such as JA, ethylene, ABA, auxins, cytokinins, and ROS regulate development and disease resistance. For instance, BTH inhibits the growth by the suppression of auxin and the down regulation of several genes involved in auxin perception, transport and signaling [126,127]. In addition, BTH affects auxin homeostasis through the activation of the expression of gene encoding GH3.5. This family of adenylating enzymes conjugates acyl substrates, such as IAA to the Asp amino-acid [128].

4.2. Priming Effect

Several researchers attempted to identify compounds that induce SAR without affecting plant growth in the field [129]. Another form of plant defense is priming, a phenomenon, which is defined as the enhancement of the basal level of resistance in plants, resulting in a faster and stronger resistance response following subsequent pathogen attack [130]. Defense priming can be regarded as an efficient mechanism to manipulate the “trade-off” machinery, resulting in minimizing the allocation fitness cost [129].
The discovery of immune-priming compounds started accidently with the use of probenazole to protect paddy field rice from the blast fungus and the bacterial leaf blight, and prompted the development of similar compounds, such as tiadinil and isotianil [70,79,80]. However, most of the classical activators of plant defenses can induce priming when used at lower doses that are insufficient to trigger detectable levels of defense responses. For instance, BABA primes host plants to activate SA-dependent signaling system [45,46] or other signaling systems, depending on the nature of challenging pathogen [131]. BTH and INA were able to prime a wide range of cellular responses, including alterations in ion transport across the plasma membrane, enhanced synthesis of phytoalexins, cell wall phenolics and lignin-like polymers, and activation of various defense genes [106,132].
Although still poorly understood, the molecular basis of priming started to be unraveled. NPR1 plays important role in inducing high levels of chromatin modification on promoters of the transcription factor genes. Priming involves a cyclic non-protein amino acid pipecolic acid as mobile signal and MAPK. Beckers et al. [133] showed that pre-stress deposition of MAPK3 and MAPK6 plays an important role during BTH-induced priming in A. thaliana. Exposure to the challenges of stressors results in the phosphorylation and activation of these two kinases in primed plants relative to non-primed plants, which is linked to enhanced defense gene expression. Priming is controlled epigenetically and relies on the ability of plant to reprogram the pattern of expression of thousands of genes. The process is initiated through the Arabidopsis subtilase SBT3.3, a proteolytic extracellular enzyme, which is involved in activation of chromatin remodeling, covalent histone modifications and defense genes become poised for enhanced activation following pathogen attack [3,134]. During priming, BTH increased acetylation of histone H3 at Lys-9 (H3K9ac) and trimethylation of histone H3 at Lys-4 (H3K4me3) in the promoter regions of the transcription factors WRKY6, WRKY29, and WRKY52 [135]. In addition, DNA methylation and histone modifications are regulated by RNA Polymerase V [136] and are involved in the transmission of a priming state or stress memory, suggesting that plants may inherit priming sensitization [137]. Transgenerational epigenetic effect of priming was reported to be triggered by BABA in Arabidopsis [138], and more recently in the potato relative Solanum physalifolium [139]. This effect could be considered as robust and a broadly distributed mechanism of phenotypic plasticity to plant diseases. Therefore, screening for new immune-priming compounds is highly needed.

4.3. Screening for New Compounds

Evaluation of new compounds requires a large quantity of chemicals and is time and space consuming, thus restricting the range of chemicals that can be tested. Large-scale screening of a broad range of compounds led to the identification of several functional SA analogues that could be used as plant activators in the field of crop protection [11,138].
The first high-throughput screening method involves young seedlings that are grown in liquid, facilitating the uniform application of chemicals from small-molecule libraries in standard 96-well plates [54]. This system is based on the use of β-glucuronidase (GUS) histochemical staining assay and the promoter of CaBP22 of A. thaliana gene, which encode a putative calmodulin-like binding protein. Screening of collection of 42,000 various molecules allowed the identification of the plant defense inducers DCA and 2-(5-bromo-2-hydroxy-phenyl)-thiazolidine-4-carboxylic acid (BHTC), which act, respectively in NPR1 independent and in NPR1 dependent manners [54,140]. By using the same system Bektas et al. identified a new compound named 2,4-dichloro-6-{(E)-((3-methoxyphenyl)imino)methyl}phenol (DPMP), which acts as a partial agonist of SA [141].
A combination of this system with GUS fused to the promoters of A. thaliana defense-related genes that are involved in SA and JA/ET signaling allowed the identification of PPA [142,143] and thienopyrimidine-type compounds [112]. To avoid unfavorable side effects, such as phytotoxicity, and to distinguish between compounds that directly activate plant defenses responses from those doing so exclusively in the presence of the pathogen, Noutoshi et al., established a new high throughput screening technique based on the use of the pathosystem Arabidopsis suspension-cultured cells/P. syringae with 96 well plates [11]. This system allowed for the elimination of compounds that induce cell death, evaluated after Evans blue staining and identification of compounds that promote pathogen resistance in Arabidopsis by invoking the hypersensitive cell death pathway in response to pathogen attack. Five new immune-priming compounds were selected from a chemical library of 10,000 molecules were called imprimatins A1, A2, A3, B1, and B2 (Table 5). Two of them acted by inhibiting SAGT, allowing then, SA accumulation. To access the effect of these new immune-priming compounds on the growth, Arabidopsis seeds were germinated and grown in liquid MS media containing imprimatins. In contrast to tiadinil, which prominently inhibited seedling growth, imprimatin A2, B1, and B2 exhibited only moderate growth inhibitory effects, in a concentration-dependent manner. However, imprimatin A1 and A3 did not affect at all the growth at the concentration range effective for immune priming [12].
Using this screening strategy, Noutoshi et al. isolated imprimatins C that behave as functional analogues of SA [12]. They effectively induce the expression of PR1 gene and enhance disease resistance in A. thaliana, however, they lack antagonistic activity against JA [12]. Furthermore, structure-activity relationship analyses implicated that the potential downstream metabolites of imprimatin C compounds, including 4-chlorobenzoic acid, 3,4-dichlorobenzoic acid, and their derivative 3,5-DCBA also act as partial agonists of SA with various potencies [13]. Therefore, imprimatin C compounds can potentially assist to better understand the molecular events that are involved in SA defense signaling and their putative functional metabolites can serve as valuable tools to address the complexity intrinsic on the activities of SA receptors, providing insights into the mechanisms governing early SA perception and NPR1 regulation and its role in plant immune signaling.

5. Conclusions

The activation of induced resistance using functional analogues of SA requires large energy input, and thus compromises other metabolic processes. Therefore, their success may depend on managing the tradeoff between defense and growth. There are many evidences that signaling crosstalks are involved in the tradeoff. Identification of signaling components that directly affect these crosstalk and designing new compounds that will affect these components will be the most important challenge for crop protection. The discovery of NPR1 as receptor of SA will be very helpful for future chemical screening of immune-priming compounds that destabilize NPR1 by binding to SA [145]. Understanding of the molecular mechanisms underlying priming may also help to design new chemicals that stimulate the plant’s inherent disease resistance mechanisms.


This work was supported by the University Chouaib Doukkali, El Jadida, Morocco.

Author Contributions

M.F. wrote the first draft. L.F. contributed to the overall preparation of the manuscript and provided the technical guidance and editing support.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Burketova, L.; Trda, L.; Ott, P.G.; Valentova, O. Bio-based resistance inducers for sustainable plant protection against pathogens. Biotechnol. Adv. 2015, 33, 994–1004. [Google Scholar] [CrossRef] [PubMed]
  2. Postel, S.; Kommerling, B. Plant systems for recognition of pathogen-associated molecular patterns. Semin. Cell Dev. Biol. 2009, 20, 1025–1031. [Google Scholar] [CrossRef] [PubMed]
  3. Spoel, S.H.; Dong, X. How do plants achieve immunity defense without specialized immune cells. Nat. Rev. Immunol. 2012, 12, 89–100. [Google Scholar] [CrossRef] [PubMed]
  4. Pitecschke, A.; Hirt, H. Disentangling the complexicity of mitogen-activated protein kinase and oxygen species signaling. Plant Physiol. 2009, 149, 606–615. [Google Scholar] [CrossRef] [PubMed]
  5. Meng, X.; Zhang, S. MAPK cascades in plant disease resistance signaling. Annu. Rev. Phytopathol. 2013, 51, 245–266. [Google Scholar] [CrossRef] [PubMed]
  6. Henry, E.; Yadeta, K.A.; Coaker, G. Recognition of bacterial plant pathogens: Local, systemic and transgenerational immunity. New Phytol. 2013, 199, 808–815. [Google Scholar] [CrossRef] [PubMed]
  7. Vlot, A.C.; Dempsey, D.A.; Klessig, D.F. Salicylic acid, a multi-faceted hormone to combat disease. Annu. Rev. Phytopathol. 2009, 47, 177–206. [Google Scholar] [CrossRef] [PubMed]
  8. Pieterse, C.M.J.; Leon-Reyes, A.; van der Does, D.; Verhage, A.; Koornneef, A.; van Pelt, J.A.; van Wees, S.C.M. Networking by small-molecule hormones in plant immunity. Induced resistance against insects and diseases. IOBC-WPRS Bull. 2012, 83, 77–80. [Google Scholar]
  9. Bektas, Y.; Eulgem, T. Synthetic plant defense elicitors. Front. Plant Sci. 2015, 5, 804. [Google Scholar] [CrossRef] [PubMed]
  10. Canet, J.V.; Dobon, A.; Ibanez, F.; Perales, L.; Tornero, P. Resistance and biomass in Arabidopsis: A new model for salicylic acid perception. Plant Biotechnol. J. 2010, 8, 126–141. [Google Scholar] [CrossRef] [PubMed][Green Version]
  11. Noutoshi, Y.; Okazaki, M.; Kida, T.; Nishina, Y.; Morishita, Y.; Ogawa, T. Novel plant immune-priming compounds identified via high throughput chemical screening target salicylic acid glucosyltransferase in Arabidopsis. Plant Cell 2012, 24, 3795–3804. [Google Scholar] [CrossRef] [PubMed]
  12. Noutoshi, Y.; Okazaki, M.; Shirasu, K. Isolation and characterization of the plant immune-priming compounds Imprimatin B3 and-B4, potentiators of disease resistance in Arabidopsis thaliana. Plant Signal. Behav. 2012, 7, 1526–1528. [Google Scholar] [CrossRef] [PubMed]
  13. Noutoshi, Y.; Ikeda, M.; Saito, T.; Osada, H.; Shirasu, K. Sulfonamides identified as plant immune-priming compounds in high throughput chemical screening increased disease resistance in Arabidopsis thaliana. Front. Plant Sci. 2012, 3, 245. [Google Scholar] [CrossRef] [PubMed]
  14. Love, A.J.; Yun, B.W.; Laval, V.; Loake, G.J.; Milner, J.J. Cauliflower mosaic virus, a compatible pathogen of Arabidopsis, engages three distinct defence signaling pathways and activates rapid systemic generation of reactive oxygen species. Plant Physiol. 2005, 139, 935–948. [Google Scholar] [CrossRef] [PubMed][Green Version]
  15. Kachroo, P.; Yoshioka, K.; Shah, J.; Dooner, H.K.; Klessig, D.F. Resistance to turnip crinkle virus in Arabidopsis is regulated by two host genes and is salicylic acid dependent but NPR1, ethylene, and Jasmonate independent. Plant Cell 2000, 12, 677–690. [Google Scholar] [CrossRef] [PubMed]
  16. Anand, A.; Uppalapati, S.R.; Ryu, C.M.; Allen, S.N.; Kang, L.; Tang, Y.H.; Mysore, K.S. Salicylic acid and systemic acquired resistance play a role in attenuating crown gall disease caused by Agrobacterium tumefaciens. Plant Physiol. 2008, 146, 703–715. [Google Scholar] [CrossRef] [PubMed]
  17. Sparla, F.; Rotino, L.; Valgimigli, M.C.; Pupillo, P.; Trost, P. Systemic resistance induced by benzothiadiazole in pear inoculated with the agent of fire blight (Erwinia amylovora). Sci. Hortic. 2004, 101, 269–279. [Google Scholar] [CrossRef]
  18. Thomma, B.P.H.J.; Tierens, K.F.M.; Penninck, I.A.M.A.; Mauch-Mani, B.; Broekaert, W.F.B.; Cammue, B.P.A. Different micro-organisms differentially induce Arabidopsis disease response pathways. Plant Physiol. Biochem. 2001, 39, 673–680. [Google Scholar] [CrossRef]
  19. Genger, R.; Jurkowski, G.; McDowell, J.; Lu, H.; Jung, H.; Greenberg, J.; Bent, A. Signaling pathways that regulate the enhanced disease resistance of Arabidopsis “defense, no death” mutants. Mol. Plant-Microbe Interact. 2008, 21, 1285–1296. [Google Scholar] [CrossRef] [PubMed]
  20. Nakashita, H.; Yoshioka, K.; Yasuda, M.; Nitta, T.; Arai, Y.; Yoshida, S.; Yamaguchi, I. Probenazole induces systemic acquired resistance in tobacco through salicylic acid accumulation. Physiol. Mol. Plant Pathol. 2002, 61, 197–203. [Google Scholar] [CrossRef]
  21. Spletzer, M.E.; Enyedi, A.J. Salicylic acid induces resistance to Alternaria solani in hydroponica. Phytopathology 1999, 89, 722–727. [Google Scholar] [CrossRef] [PubMed]
  22. Yao, H.J.; Tian, S.P. Effects of a biocontrol agent and methyl jasmonate on postharvest diseases of peach fruit and the possible mechanisms involved. J. Appl. Microbiol. 2005, 98, 941–950. [Google Scholar] [CrossRef] [PubMed]
  23. Ferrari, S.; Plotnikova, J.M.; De Lorenzo, G.; Ausubel, F.M. Arabidopsis local resistance to Botrytis cinérea involves salicylic acid and camalexin and requires EDS4 and PAD2, but not SID2, EDS5 or PAD4. Plant J. 2003, 35, 193–205. [Google Scholar] [CrossRef] [PubMed]
  24. Lee, H.I.; Leon, J.; Raskin, I. Biosynthesis and metabolism of salicylic acid. Proc. Natl. Acad. Sci. USA 1995, 92, 4076–4079. [Google Scholar]
  25. Wildermuth, M.C.; Dewdney, J.; Wu, G.; Ausubel, F.M. Isochorismate synthesis is required to synthesize salicylic acid for plant defense. Nature 2001, 414, 560–565. [Google Scholar] [CrossRef] [PubMed]
  26. Reddy, A.S.N.; Ali, G.S.; Celesnik, H.; Day, I.S. Coping with stresses: Roles of calcium- and calcium/calmodulin-regulated gene expression. Plant Cell 2011, 23, 2010–2032. [Google Scholar] [CrossRef] [PubMed]
  27. Diaz-Vivancos, P.; Bernal-Vicente, A.; Cantabella, D.; Petri, C.; Hernandez, J.A. Metabolomics and biochemical approaches link salicylic acid biosynthesis to cyanogenesis in peach plants. Plant Cell Physiol. 2017, 58, 2057–2066. [Google Scholar] [CrossRef] [PubMed]
  28. Cui, H.; Gobbato, E.; Kracher, B.; Qui, J.; Parker, J.E. A core function of EDS1 with PAD4 is to protect salicylic acid defense sector in Arabidopsis immunity. New Phytol. 2017, 213, 1802–1817. [Google Scholar] [CrossRef] [PubMed]
  29. Rustérucci, C.; Aviv, D.H.; Holt, B.F.; Dangl, J.L.; Parker, J.E. The disease resistance signaling components EDS1 and PAD4 are essential regulators of the cell death pathway controlled by LSD1 in Arabidopsis. Plant Cell 2001, 13, 2211–2224. [Google Scholar] [CrossRef] [PubMed]
  30. Rietz, S.; Stamm, A.; Malonek, S.; Wagner, S.; Becker, D.; Medina-Escobar, N.; Vlot, A.C.; Feys, B.J.; Niefind, K.; Parker, J.E. Different roles of enhanced disease susceptibility 1 (EDS1) bound to and dissociated from phytoalexin deficient 4 (PAD4) in Arabidopsis immunity. New Phytol. 2011, 191, 107–119. [Google Scholar] [CrossRef] [PubMed]
  31. Nawrath, C.; Heck, S.; Parinthawong, N.; Metraux, J.P. EDS5, an essential component of salicylic acid-dependent signaling for disease resistance in Arabidopsis, is a member of the MATE transporter family. Plant Cell 2002, 14, 275–286. [Google Scholar] [CrossRef] [PubMed]
  32. Gupta, V.; Willits, M.G.; Glazebrook, J. Arabidopsis thaliana EDS4 contributes to salicylic acid (SA)-dependent expression of defense responses: Evidence for inhibition of jasmonic acid signaling by SA. Mol. Plant-Microbe Interact. 2000, 13, 503–511. [Google Scholar] [CrossRef] [PubMed]
  33. Glazebrook, J. Contrasting mechanisms of defense against biotrophic and necrotrophic pathogens. Annu. Rev. Phytopathol. 2005, 43, 205–227. [Google Scholar] [CrossRef] [PubMed]
  34. Yamasaki, K.; Motomura, Y.; Yagi, Y.; Nomura, H.; Kikuchi, S.; Nakai, M.; Shiina, T. Chloroplast envelope localization of EDS5, an essential factor for salicylic acid biosynthesis in Arabidopsis thaliana. Plant Signal. Behav. 2013, 8, e23603. [Google Scholar] [CrossRef] [PubMed]
  35. Park, S.W.; Kaimoyo, E.; Kumar, D.; Mosher, S.; Klessig, D.F. Methyl salicylate is a critical mobile signal for plant systemic acquired resistance. Science 2007, 318, 113–116. [Google Scholar] [CrossRef] [PubMed]
  36. Návarová, H.; Bernsdorff, F.; Döring, A.C.; Zeier, J. Pipecolic acid, an endogenous mediator of defense amplifi cation and priming, is a critical regulator of inducible plant immunity. Plant Cell 2012, 24, 5123–5141. [Google Scholar] [CrossRef] [PubMed]
  37. Jung, H.W.; Tschaplinski, T.J.; Wang, L.; Glazebrook, J.; Greenberg, J.T. Priming in systemic plant immunity. Science 2009, 324, 89–91. [Google Scholar] [CrossRef] [PubMed]
  38. Chaturvedi, R.; Venables, B.; Petros, R.A.; Nalam, V.; Li, M.; Wang, X.; Takemoto, L.J.; Shah, J. An abietane diterpenoid is a potent activator of systemic acquired resistance. Plant J. 2012, 71, 161–172. [Google Scholar] [CrossRef] [PubMed]
  39. Zhang, Z.; Li, Q.; Staswick, P.E.; Wang, M.; Zhu, Y.; He, Z. Dual regulation role of GH3.5 in salicylic acid and auxin signaling Arabidopsis-Pseudomonas syringae interaction. Plant Physiol. 2007, 145, 450–464. [Google Scholar] [CrossRef] [PubMed]
  40. Fu, Z.Q.; Yang, S.; Saleh, A.; Wang, W.; Ruble, J.; Oka, N.; Mohan, R.; Spoel, S.H.; Tada, Y.; Zheng, N.; et al. NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants. Nature 2012, 486, 228–232. [Google Scholar] [CrossRef] [PubMed][Green Version]
  41. Wu, Y.; Zhang, D.; Chu, J.Y.; Boyle, P.; Wang, Y.; Brindle, I.D.; De Luca, V.; Despres, C. The Arabidopsis NPR1 protein is a receptor for the plant defense hormone salicylic acid. Cell Rep. 2012, 1, 639–647. [Google Scholar] [CrossRef] [PubMed]
  42. Lebel, E.; Heifetz, P.; Thorne, L.; Uknes, S.; Ryals, J.; Ward, E. Functional analysis of regulatory sequences controlling PR-1 gene expression in Arabidopsis. Plant J. 1998, 16, 223–233. [Google Scholar] [CrossRef] [PubMed]
  43. Moreau, M.; Tian, M.; Klessig, D.F. Salicylic acid binds NPR3 and NPR4 to regulate NPR1-dependent defense responses. Cell Res. 2012, 22, 1631–1633. [Google Scholar] [CrossRef] [PubMed]
  44. Conrath, U.; Beckers, G.S.M.; Langenbach, C.J.G.; Jaskiewicz, M.R. Priming for enhanced defense. Annu. Rev. Phytopathol. 2015, 53, 97–119. [Google Scholar] [CrossRef] [PubMed]
  45. Zimmerli, L.; Jakab, C.; Métraux, J.P.; Mauch-Mani, B. Potentiation of pathogen specific defense mechanisms in Arabidopsis by beta-amino butyric acid. Proc. Natl. Acad. Sci. USA 2000, 97, 12920–12925. [Google Scholar] [CrossRef] [PubMed]
  46. Zimmerli, L.; Métraux, J.P.; Mauch-Mani, B. Beta amino butyric acid induced protection of Arabidopsis against the necrotrophic fungus Botrytis cinerea. Plant Physiol. 2001, 126, 517–523. [Google Scholar] [CrossRef] [PubMed]
  47. Cohen, Y.; Rubin, A.E.; Kilfin, G. Mechanisms of induced resistance in lettuce against Bremia lactuca by DL-beta-amino-butyric acid (BABA). Eur. J. Plant Pathol. 2010, 130, 13–27. [Google Scholar] [CrossRef]
  48. Sharma, K.; Bruns, C.; Butz, A.F.; Finckh, M.R. Effect of fertilizers and plant strengthners on the susceptibility of tomatoes to single and mixed isolates of Phytophthora infestans. Eur. J. Plant Pathol. 2012, 133, 739–751. [Google Scholar] [CrossRef]
  49. Sasek, V.; Novakova, M.; Dobrev, R.I.; Valentova, O.; Burketova, L. B-amino butyric acid protects Brassica napus plants from infection by Leptosphaeria maculans. Resistance induction or a direct antifungal effect. Eur. J. Plant Pathol. 2012, 133, 279–289. [Google Scholar] [CrossRef]
  50. Harm, A.; Kassemeyer, H.H.; Seibicke, T.; Regner, F. Evolution of chemical and natural resistance inducers against downy mildew (Plasmopara viticola) in grapevine. Am. J. Enol. Vitic. 2011, 62, 184–192. [Google Scholar] [CrossRef]
  51. Liljeroth, E.; Bengtsson, T.; Wiik, L.; Andreasson, E. Induced resistance in potato to Phytphthora infestans—Effects of BABA in greenhouse and field tests with different potato varieties. Eur. J. Plant Pathol. 2010, 127, 171–183. [Google Scholar] [CrossRef]
  52. Bengtsson, T.; Weighill, D.; Proux-Wera, E.; Levander, F.; Resjö, S.; Dahar Burra, D.; Moushib, L.I.; Hedley, P.; Liljeroth, E.; Jacobson, D.; et al. Proteomics and transcriptomics of the BABA-induced resistance response in potato using a novel functional annotation approach. BMC Genom. 2014, 15, 315. [Google Scholar] [CrossRef] [PubMed]
  53. Bengtsson, T.; Holefors, A.; Witzell, J.; Andreasson, E.; Liljeroth, E. Activation of defence responses to Phytophthora infestans in potato by BABA. Plant Pathol. 2014, 63, 193–202. [Google Scholar] [CrossRef]
  54. Knoth, C.; Salus, M.S.; Girke, T.; Eulgem, T. The synthetic elicitor 3,5-dichloroanthranilic acid induces NPR1-dependent and NPR1-independent mechanisms of disease resistance in Arabidopsis. Plant Physiol. 2009, 150, 333–347. [Google Scholar] [CrossRef] [PubMed]
  55. Conrath, U.; Chen, Z.; Ricigliano, J.R.; Klessig, D.F. Two inducers of plant defense responses, 2,6-dichloroisonicotinec acid and salicylic acid, inhibit catalase activity in tobacco. Proc. Natl. Acad. Sci. USA 1995, 92, 7143–7147. [Google Scholar] [CrossRef] [PubMed]
  56. Enyong, A.B. Synthesis of Novel Agrochemicals as Potential Plant Immunization Agents. Master’s Thesis, East Tennessee State University, Johnson City, TN, USA, 2008. [Google Scholar]
  57. Cui, Z.; Ito, J.; Dohi, H.; Amemiya, Y.; Nishida, Y. Molecular design and synthesis of novel salicyl glycoconjugates as elicitors against plant diseases. PLoS ONE 2014, 9, e108338. [Google Scholar] [CrossRef] [PubMed]
  58. Song, G.C.; Choi, H.K.; Ryu, C.M. The folate precursor para-aminobenzoic acid elicits induced resistance against Cucumber mosaic virus and Xanthomonas axonopodis. Ann. Bot. 2013, 111, 925–934. [Google Scholar] [CrossRef] [PubMed]
  59. Bhattarai, K.K.; Atamian, H.S.; Kaloshia, I.; Eulgem, T. WRKY72-type transcription factors contribute to basal immunity in tomato and Arabidopsis as well as gene-for-gene resistance mediated by the tomato R gene Mi-1. Plant J. 2010, 63, 229–240. [Google Scholar] [CrossRef] [PubMed]
  60. Metraux, J.P.; Ahlgoy, P.; Staub, T.; Speich, J.; Steinemann, A.; Ryals, J.; Ward, E. Induced systemic resistance in cucumber in response to 2,6-dichloro-isonicotinic acid and pathogens. In Advances in Molecular Genetics of Plant-Microbe Interactions; Hennecke, H., Verma, D., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1991. [Google Scholar]
  61. Ward, E.R.; Uknes, S.J.; Williams, S.C.; Dincher, S.S.; Wiederhold, D.L.; Alexander, D.C.; Ahl-Goy, P.; Métraux, J.P.; Ryals, J.A. Coordinate gene activity in response to agents that induce systemic acquired resistance. Plant Cell 1991, 3, 1085–1094. [Google Scholar] [CrossRef] [PubMed]
  62. Delaney, T.P.; Friedrich, L.; Ryals, J.A. Arabidopsis signal transduction mutant defective in chemically and biologically induced disease resistance. Proc. Natl. Acad. Sci. USA 1995, 92, 6602–6606. [Google Scholar] [CrossRef] [PubMed]
  63. Vernooij, B.; Friedrich, L.; Goy, P.A.; Staub, T.; Kessmann, H.; Ryals, J. 2,6-dicholoroisonicotinic acid-induced resistance to pathogens without the accumulation of saliciylic acid. Mol. Plant-Microbe Interact. 1995, 8, 228–234. [Google Scholar] [CrossRef]
  64. Durner, J.; Klessig, D.F. Inhibition of ascorbate peroxidase by salicylic acid and 2,6-dichloroisonicotinic acid, two inducers of plant defense responses. Proc. Natl. Acad. Sci. USA 1995, 92, 11312–11316. [Google Scholar] [CrossRef] [PubMed]
  65. Yoshida, H.; Konishi, K.; Koike, K.; Nakagawa, T.; Sekido, S.; Yamaguchi, I. Effect of N-cyanomethyl-2-chloroisonicotinamide for control of rice blast. J. Pestic. Sci. 1990, 15, 413–417. [Google Scholar] [CrossRef]
  66. Yasuda, M. Regulation mechanisms of systemic acquired resistance induced by plant activators. J. Pestic. Sci. 2007, 32, 281–282. [Google Scholar] [CrossRef]
  67. Naim, M.J.; Alam, O.; Nawaz, F.; Alam, M.J.; Alam, P. Current status of pyrazole and its biological activities. J. Pharm. Bioallied Sci. 2016, 8, 2–17. [Google Scholar] [PubMed]
  68. Jee Kashyap, S.; Kumar Garg, V.; Kumar Sharma, P.; Kumar, N.; Dudher, R.; Kumar Gupta, J. Thiadiazoles: Having diverse biological activities. Med. Chem. Res. 2012, 21, 2123–2132. [Google Scholar] [CrossRef]
  69. Kumar Jain, A.; Sharma, S.; Vaidya, A.; Ravichandran, V.; Agrawal, R.K. 1,3,4-thiadiazole and its derivatives: A review on recent progress in biological activities. Chem. Biol. Drug Dis. 2013, 81, 557–576. [Google Scholar] [CrossRef] [PubMed]
  70. Nakashita, H.; Yoshioka, K.; Takayama, M.; Kuga, R.; Midon, N.; Usami, R.; Horikoshi, K.; Yoneyama, K.; Yamaguchi, I. Characterization of PBZ1, a probenazole-inducible gene, in suspension-cultured rice cells. Biosci. Biotechnol. Biochem. 2001, 65, 205–208. [Google Scholar] [CrossRef] [PubMed]
  71. Kunz, W.; Schurter, R.; Maetzke, T. The chemistry of benzothiadiazole plant activators. Pest Manag. Sci. 1997, 50, 275–282. [Google Scholar] [CrossRef]
  72. Nakashita, A.; Inoue, E.; Watanabe-Takahashi, A.; Yamaya, T.; Takahashi, H. Transcriptome profiling of sulfur-responsive genes in Arabidopsis reveals global effect on sulfur nutrition on multiple metabolic pathways. Plant Physiol. 2003, 132, 597–605. [Google Scholar] [CrossRef] [PubMed]
  73. Nishioka, M.; Nakashita, H.; Yasuda, M.; Yoshida, S.; Yamaguchi, I. Induction of resistance against rice bacterial leaf blight by 3-chloro-1-methyl-1-pyrazole-5-carboxylic acid. J. Pestic. Sci. 2005, 30, 47–49. [Google Scholar] [CrossRef]
  74. Yasuda, M.; Nishioka, M.; Nakashita, H.; Yamaguchi, I.; Yoshida, S. Pyrazole carboxylic acid derivative induces systemic acquired resistance in tobacco. Biosci. Biotechnol. Biochem. 2003, 67, 2614–2620. [Google Scholar] [CrossRef] [PubMed]
  75. Oostendorp, M.; Kunz, W.; Dietrich, B.; Staub, T. Induced disease resistance in plants by chemicals. Eur. J. Plant Pathol. 2001, 107, 19–28. [Google Scholar] [CrossRef]
  76. Boyle, C.; Walters, D.R. Saccharin-induced protection against powdery mildew in barley: Effects on growth and phenylpropanoid metabolism. Plant Pathol. 2006, 55, 82–91. [Google Scholar] [CrossRef]
  77. Boyle, C.; Walters, D.R. Induction of systemic protection against rust infection in broad bean by saccharin: Effects on plant growth and development. New Phytol. 2005, 167, 607–612. [Google Scholar] [CrossRef] [PubMed]
  78. Srivastava, G.S.; Marois, J.J.; Wright, D.L.; Walker, D.R. Saccharin-induced systemic acquired resistance against rust (Phakopsora pachyrhizi) infection in soybean: Effects on growth and development. Crop Prot. 2011, 30, 726–732. [Google Scholar] [CrossRef]
  79. Ogava, M.; Kadowaki, A.; Yamada, T.; Kadooka, O. Applied Development of a Novel Fungicide Isotianil (Stout); R&D Report, No.I; Health & Crop Sciences Research Laboratory, Sumitomo Chemical Co., Ltd.: Takarazuka, Japan, 2011; pp. 1–16. [Google Scholar]
  80. Toquin, V.; Sirven, C.; Assmann, L.; Sawada, H. Host defense inducers. In Modern Crop Protection Compounds 2, 2nd ed.; Kramer, W., Schrimer, U., Jeschke, P., Witschel, M., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2012. [Google Scholar]
  81. Schirmer, U.; Jeschke, P.; Witschel, M. Modern Crop Protection Compounds; John Wiley & Sons: Hoboken, NJ, USA, 2012. [Google Scholar]
  82. Brisset, M.N.; Faize, M.; Heintz, C.; Cesbro, S.; Tharaud, M.; Paulin, J.P. Induced resistance to Erwinia amylovora in apple and pear. Acta Hortic. 2002, 590, 449–450. [Google Scholar] [CrossRef]
  83. Graham, J.H.; Myers, M.E. Soil application of SAR inducers imidacloprid, thiamethoxam, and Acibenzolar-S-methyl for citrus canker control in young grapefruit trees. Plant Dis. 2011, 95, 725–728. [Google Scholar] [CrossRef]
  84. Potlakayala, S.D.; Reed, D.W.; Covello, P.S.; Fobert, P.R. Systemic acquired resistance in canola is linked with pathogenesis-related gene expression and requires salicylic acid. Phytopathology 2007, 97, 794–802. [Google Scholar] [CrossRef] [PubMed]
  85. Faize, M.; Faize, L.; Koike, N.; Ishizaka, M.; Ishii, H. Acibenzolar-S-methyl-induced resistance to Japanese pear scab is associated with potentiation of multiple defense responses. Phytopathology 2004, 94, 604–612. [Google Scholar] [CrossRef] [PubMed]
  86. Latunde-Dada, A.O.; Lucas, J.A. The plant defence activator acidbenzolar-S-methyl primes cowpea [Vigna unguiculata (L.) Walp.] seedlings for rapid induction of resistance. Physiol. Mol. Plant Pathol. 2001, 58, 199–208. [Google Scholar] [CrossRef]
  87. Friedrich, L.; Lawton, K.; Ruess, W.; Masner, P.; Specker, N.; Rella, M.G.; Meier, B.; Dincher, S.; Staub, T.; Uknes, S.; et al. A benzothiadiazole derivative induces systemic acquired resistance in tobacco. Plant J. 1996, 10, 61–70. [Google Scholar] [CrossRef]
  88. Mandal, B.; Mandal, S.; Csinos, A.S.; Martinez, N.; Culbreath, A.K.; Pappu, H.R. Biological and molecular analyses of the acibenzolar-S-methyl-induced systemic acquired resistance in flue-cured tobacco against Tomato spotted wilt virus. Phytopathology 2008, 98, 196–204. [Google Scholar] [CrossRef] [PubMed]
  89. Anfoka, G.H. Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester induces systemic resistance in tomato (Lycopersicon esculentum Mill cv. Vollendung) to Cucumber mosaic virus. Crop Prot. 2000, 19, 401–405. [Google Scholar] [CrossRef]
  90. Soylu, S.; Baysal, O.; Soylu, E.M. Induction of disease resistance by the plant activator, acibenzolar-S-methyl (ASM), against bacterial canker (Clavibacter michiganensis subsp. michiganensis) in tomato seedlings. Plant Sci. 2003, 165, 1069–1075. [Google Scholar] [CrossRef]
  91. Zine, H.; Rifai, L.A.; Faize, M.; Smaili, A.; Makroum, K.; Belfaiza, M.; Kabil, E.M.; Koussa, T. Duality of acibenzolar-S-methyl in the inhibition of pathogen growth and induction of resistance during the interaction tomato/Vertcillium dahliae. Eur. J. Plant Pathol. 2016, 145, 61–69. [Google Scholar] [CrossRef]
  92. Liu, S.Y.; Liu, Z.; Fitt, B.D.L.; Evans, N.; Foster, S.J.; Huang, Y.J.; Latunde-Dada, A.O.; Lucas, J.A. Resistance to Leptosphaeria maculans (phoma stem canker) in Brassica napus (oilseed rape) induced by L. biglobosa and chemical defence activators in field and controlled environments. Plant Pathol. 2006, 55, 401–412. [Google Scholar] [CrossRef]
  93. Du, Q.; Zhu, W.; Zhao, Z.; Qian, X.; Xu, Y. Novel benzo-1,2,3-thiadiazole-7-carboxylate derivatives as plant activators and the development of their agricultural applications. J. Agric. Food Chem. 2012, 60, 346–353. [Google Scholar] [CrossRef] [PubMed]
  94. Yasuda, M.; Kusajima, M.; Nakajima, M.; Akutsu, K.; Kudo, T.; Yoshida, S.; Nakashita, H. Thiadiazole carboxylic acid moiety of tiadinil, SV-03, induces systemic acquired resistance in tobacco without salicylic acid accumulation. J. Pestic. Sci. 2006, 31, 329–334. [Google Scholar] [CrossRef]
  95. Yoshida, K.; Ogino, A.; Yamada, K.; Sonoda, R. Induction of disease resistance in tea (Camellia sinensis L.) by plant activators. JARQ 2010, 44, 391–398. [Google Scholar] [CrossRef]
  96. Zine, H.; Rifai, L.A.; Faize, M.; Bentiss, F.; Guesmi, S.; Laachir, A.; Smaili, A.; Makroum, K.; Sahibed-Dine, A.; Koussa, T. Resistance induced in tomato plants against Vertcillium wilt by the binuclear nickel coordination complex of the ligand 2,5-bis(pyridine-2-yl)-1,3,4-thiadiazole. J. Agric. Food Chem. 2016, 64, 2661–2667. [Google Scholar] [CrossRef] [PubMed]
  97. Zine, H.; Rifai, L.A.; Koussa, T.; Bentiss, F.; Guesmi, S.; Laachir, A.; Makroum, K.; Belfaiza, M.; Faize, M. The mononuclear nickel (II) complex bis(azido-kN)bis[2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole-κ(2)N(2),N(3)]nickel(II) protects tomato from Verticillium dahliae by inhibiting the fungal growth and activating plant defenses. Pest Manag. Sci. 2017, 73, 188–197. [Google Scholar] [CrossRef] [PubMed]
  98. Smaili, A.; Rifai, L.A.; Koussa, T.; Bentiss, F.; Laachir, A.; Guesmi, S.; Faize, M. Copper complexes of the 1,3,4-thiadiazole derivatives modulate antioxidant defense responses and resistance in tomato plants against fungal and bacterial diseases. Pestic. Biochem. Physiol. 2017, 143, 26–32. [Google Scholar] [CrossRef] [PubMed]
  99. Umemura, K.; Satou, J.; Iwata, M.; Uozumi, N.; Koga, J.; Kawano, T.; Anzai, H.; Mitomi, M. Contribution of salicylic acid glucosyltransferase, OSSGT1, to chemically induced disease resistance in rice plants. Plant J. 2009, 57, 463–472. [Google Scholar] [CrossRef] [PubMed]
  100. Yoshioka, K.; Nakashita, H.; Klessig, D.F.; Yamaguchi, I. Probenazole induces systemic acquired resistance in Arabidopsis with a novel type of action. Plant J. 2001, 25, 149–157. [Google Scholar] [CrossRef] [PubMed]
  101. Molina, A.; Hunt, M.D.; Ryals, J.A. Impaired fungicide activity in plants blocked in disease resistance signal transduction. Plant Cell 1998, 10, 1903–1914. [Google Scholar] [CrossRef] [PubMed]
  102. Lawton, K.A.; Friedrich, L.; Hunt, M.; Weymann, K.; Delaney, T.; Kessmann, H.; Staub, T.; Ryals, J. Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway. Plant J. 1996, 10, 71–82. [Google Scholar] [CrossRef] [PubMed]
  103. Wendehenne, D.; Durner, J.; Chen, Z.; Klessig, D.F. Benzothiadiazole, an inducer of plant defenses, inhibits catalase and ascorbate peroxidase. Phytochemistry 1998, 47, 651–657. [Google Scholar] [CrossRef]
  104. Tripathi, D.; Jiang, Y.L.; Kumar, D. SABP2, a methylsalicylate esterase is required for the systemic acquired resistance induced by acibenzolar-S-methyl in plants. FEBS Lett. 2010, 584, 3458–3463. [Google Scholar] [CrossRef] [PubMed]
  105. Faize, M.; Faize, L.; Ishii, H. Gene expression during acibenzolar-S-methyl-induced priming for potentiated responses to Venturia nashicola Japanese pear. J. Phytopathol. 2009, 157, 137–144. [Google Scholar] [CrossRef]
  106. Faize, M.; Faize, L.; Ishii, H. Characterization of a leucine-rich repeat receptor like kinase (LRPK) gene from Japanese pear and its expression analysis upon scab infection and acibenzolar-S-methyl treatment. J. Gen. Plant Pathol. 2007, 73, 104–112. [Google Scholar] [CrossRef]
  107. Deepak, S.A.; Ishii, H.; Park, P. Acibenzolar-S-methyl primes cell wall strengthening genes and reactive oxygen species forming/scavenging enzymes in cucumber after fungal pathogen attack. Physiol. Mol. Plant Pathol. 2006, 69, 52–61. [Google Scholar] [CrossRef]
  108. Azami-Sardooei, Z.; Seifi, H.S.; De Vleesschauwer, D.; Hofte, M. Benzothiadiazole (BTH) induced resistance against Botrytis cinerea is inversely correlated with vegetative and generative growth in bean and cucumber but not in tomato. Aust. Plant Pathol. 2013, 42, 485–490. [Google Scholar] [CrossRef]
  109. Momol, M.T.; Olson, S.M.; Funderburk, J.E.; Stavisky, J.; Marois, J.J. Integrated management of tomato spotted wilt on field-grown tomatoes. Plant Dis. 2004, 88, 882–890. [Google Scholar] [CrossRef]
  110. Tsubata, K.; Kuroda, K.; Yamamoto, Y.; Yasokawa, N. Development of a novel plant activator for rice diseases, Tiadinil. J. Pestic. Sci. 2006, 31, 161–162. [Google Scholar] [CrossRef]
  111. Sun, T.J.; Lu, Y.; Narusaka, M.; Shi, C.; Yang, Y.B.; Wu, J.X.; Zeng, H.Y.; Narusaka, Y.; Yao, N. A novel pyrimidin-like plant activator stimulates plant disease resistance and promotes growth. PLoS ONE 2015, 10, e0123227. [Google Scholar] [CrossRef] [PubMed]
  112. Narusaka, M.; Narusaka, Y. Thienopyrimidine-type compounds protect Arabidopsis plants against the hemibiotrophic fungal pathogen Colletotrichum higginsianum and bacterial pathogen Pseudomonas syringae pv. maculicola. Plant Signal. Behav. 2017, 12, e1293222. [Google Scholar] [CrossRef] [PubMed]
  113. Ford, K.A.; Casida, J.E.; Chandran, D.; Gulevich, A.G.; Okrent, R.A.; Durkin, K.A.; Sarpong, R.; Bunnelle, E.M.; Wildermuth, M.C. Neonicotinoid insicticides induce salicylate-associated plant defense responses. Proc. Natl. Acad. Sci. USA 2010, 107, 17527–17532. [Google Scholar] [CrossRef] [PubMed]
  114. Francis, M.I.; Redondo, A.; Burns, J.K.; Graham, J.H. Soil application of imidacloprid and related SAR-inducing compounds produces effective and persistent control of citrus canker. Eur. J. Plant Pathol. 2009, 22, 283–292. [Google Scholar] [CrossRef]
  115. Heil, M.; Baldwin, I.T. Fitness costs of induced resistance: Emerging experimental support for a slippery concept. Trends Plant Sci. 2002, 7, 61–67. [Google Scholar] [CrossRef]
  116. Shirano, Y.; Kachroo, P.; Shah, J.; Klessig, D.F. A gain-of-function mutation in an Arabidopsis Toll Interleukin1 receptor-nucleotide binding site-leucine-rich repeat type R gene triggers defense responses and results in enhanced disease resistance. Plant Cell 2002, 14, 3149–3162. [Google Scholar] [CrossRef] [PubMed]
  117. Zhang, Y.; Goritschnig, S.; Dong, X.; Li, X. A gain-of-function mutation in a plant disease resistance gene leads to constitutive activation of downstream signal transduction pathways in suppressor of npr1-1, constitutive 1. Plant Cell 2003, 15, 2636–2646. [Google Scholar] [CrossRef] [PubMed]
  118. Walters, D.; Heil, M. Costs and trade-offs associated with induced resistance. Physiol. Mol. Plant Pathol. 2007, 71, 3–17. [Google Scholar] [CrossRef]
  119. Huot, B.; Yao, J.; Montgomery, B.L.; He, S.Y. Growth–defense tradeoffs in plants: A balancing act to optimize fitness. Mol. Plant 2014, 7, 1267–1287. [Google Scholar] [CrossRef] [PubMed]
  120. Heil, M.; Hilpert, A.; Kaiser, W.; Linsenmair, K.E. Reduced growth and seed set following chemical induction of pathogen defence: Does systemic acquired resistance (SAR) incur allocation costs? J. Ecol. 2000, 88, 645–654. [Google Scholar] [CrossRef]
  121. Cipollini, D.F. Does competition magnify the fitness costs of induced responses in Arabidopsis thaliana? A manipulative approach. Oecologia 2002, 131, 514–520. [Google Scholar] [CrossRef] [PubMed]
  122. Heidel, A.J.; Clarke, J.D.; Antonovics, J.; Dong, X. Fitness costs of mutations affecting the systemic acquired resistance pathway in Arabidopsis thaliana. Genetics 2004, 168, 2197–2206. [Google Scholar] [CrossRef] [PubMed]
  123. Abreu, M.E.; Munné-Bosch, S. Salicylic acid deficiency in NahG transgenic lines and sid2 mutants increases seed yield in the annual plant Arabidopsis thaliana. J. Exp. Bot. 2009, 60, 1261–1271. [Google Scholar] [CrossRef] [PubMed]
  124. Prats, E.; Rubiales, D.; Jorrín, J. Acibenzolar-S-methyl-induced resistance to sunflower rust (Puccinia helianthi) is associated with an enhancement of coumarins on foliar surface. Physiol. Mol. Plant Pathol. 2002, 60, 155–162. [Google Scholar] [CrossRef]
  125. Romero, A.M.; Kousik, C.S.; Ritchie, D.F. Resistance to bacterial spot in bell pepper induced by acibenzolar-S-methyl. Plant Dis. 2001, 85, 189–194. [Google Scholar] [CrossRef]
  126. Heidel, A.J.; Dong, X. Fitness benefits of systemic acquired resistance during Hyaloperonospora parasitica infection in Arabidopsis thaliana. Genetics 2006, 173, 1621–1628. [Google Scholar] [CrossRef] [PubMed]
  127. Wang, D.; Amornsiripanitch, N.; Dong, X. A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants. PLoS Pathog. 2006, 2, e123. [Google Scholar] [CrossRef] [PubMed]
  128. Wang, D.; Pajerowska-Mukhtar, K.; Hendrickson Culler, A.; Dong, X. Salicylic acid inhibits pathogen growth in plants through repression of the auxin signaling pathway. Curr. Biol. 2007, 17, 1784–1790. [Google Scholar] [CrossRef] [PubMed]
  129. Staswick, W.P.E.; Serban, B.; Rowe, M.; Tiryaki, I.; Maldonado, M.T.; Maldonado, M.C.; Suzaa, W. Characterization of an Arabidopsis Enzyme Family That Conjugates Amino Acids to Indole-3-Acetic Acid. Plant Cell 2005, 17, 616–627. [Google Scholar] [CrossRef] [PubMed]
  130. Cipollini, D.; Heil, M. Costs and benefits of induced resistance to herbivores and pathogens in plants. Plant Sci. Rev. 2010, 5, 1–25. [Google Scholar] [CrossRef]
  131. Ton, J.; Mauch-Mani, B. Beta amino butyric acid induced resistance against necrotrophic pathogen is based on ABA-dependent priming for callose. Plant J. 2004, 38, 119–130. [Google Scholar] [CrossRef] [PubMed]
  132. Conrath, U.; Beckers, G.J.M.; Flors, V.; García-Agustín, P.; Jakab, G.; Mauch, F.; Newman, M.A.; Pieterse, C.M.; Poinssot, B.; Pozo, M.J.; et al. Priming: Getting ready for battle. Mol. Plant-Microbe Interact. 2006, 19, 1062–1071. [Google Scholar] [CrossRef] [PubMed]
  133. Kohler, A.; Schwindling, S.; Conrath, U. Benzothiazole induced priming for potentiated responses to pathogen infection, wounding, and infiltration of water into leaves requires the NPR1/NIM1 gene in Arabidopsis. Plant Physiol. 2002, 128, 1046–1056. [Google Scholar] [CrossRef] [PubMed]
  134. Beckers, G.J.; Jaskiewicz, M.; Liu, Y.; Underwood, W.R.; He, S.Y.; Zhang, S.; Conrath, U. Mitogen-activated protein kinases 3 and 6 are required for full priming of stress responses in Arabidopsis thaliana. Plant Cell 2009, 21, 944–953. [Google Scholar] [CrossRef] [PubMed]
  135. Ramirez, V.; Lopez, A.; Mauch-Mani, B.; Gil, M.J.; Vera, P. An Extracellular Subtilase Switch for Immune Priming in Arabidopsis. PLoS Pathog. 2013, 9, e1003445. [Google Scholar] [CrossRef] [PubMed]
  136. Jaskiewicz, M.; Conrath, U.; Peterhansel, C. Chromatin modification acts as a memory for systemic acquired resistance in the plant stress response. EMBO Rep. 2011, 12, 50–55. [Google Scholar] [CrossRef] [PubMed]
  137. Lopez, A.; Ramirez, V.; Garcia-Andrade, J.; Flors, V.; Vera, P. The RNA Silencing Enzyme RNA Polymerase V Is Required for Plant Immunity. PLoS Genet. 2011, 7, e1002434. [Google Scholar] [CrossRef] [PubMed][Green Version]
  138. Slaughter, A.; Daniel, X.; Flors, V.; Luna, E.; Hohn, B.; Mauch-Mani, B. Descendants of primed Arabidopsis plants exhibit resistance to biotic stress. Plant Physiol. 2012, 158, 835–843. [Google Scholar] [CrossRef] [PubMed]
  139. Lankinen, A.; Abreha, K.B.; Alexandersson, E.; Andersson, S.; Andreasson, E. Nongenetic inheritance of induced resistance in a wild annual plant. Phytopathology 2016, 106, 877–883. [Google Scholar] [CrossRef] [PubMed]
  140. Schreiber, K.J.; Nasmith, C.G.; Allard, G.; Singh, J.; Subramaniam, R.; Desveaux, D. Found in translation: High-throughput chemical screening in Arabidopsis thaliana identifies small molecules that reduce Fusarium head blight disease in wheat. Mol. Plant-Microbe Interact. 2011, 24, 640–648. [Google Scholar] [CrossRef] [PubMed]
  141. Rodriguez-Furlan, C.; Salinas-Grenet, H.; Sandoval, O.; Recabarren, C.; Arrano-Salinas, P.; Soto-Alvear, S.; Orellana, A.; Blanco Herrera, F. The root hair specific syp123 regulates the localization of cell wall components and contributes to rizhobacterial priming of induced systemic resistance. Front. Plant Sci. 2016, 7, 1081. [Google Scholar] [CrossRef] [PubMed]
  142. Bektas, Y.; Rodriguez-Salus, M.; Schroeder, M.; Gomez, A.; Kaloshian, I.; Eulgem, T. The Synthetic Elicitor DPMP (2,4-dichloro-6-{(E)-[(3-methoxyphenyl) imino]methyl}phenol) triggers strong immunity in Arabidopsis thaliana and tomato. Sci. Rep. 2016, 6, 29554. [Google Scholar] [CrossRef] [PubMed]
  143. Narusaka, Y.; Narusaka, M.; Abe, H.; Hosaka, N.; Kobayashi, M.; Shiraishi, T.; Iwabuchi, M. High-throughput screening for plant defense activators using a β-glucuronidase-reporter gene assay in Arabidopsis thaliana. Plant Biotechnol. 2009, 26, 345–349. [Google Scholar] [CrossRef]
  144. Noutoshi, Y.; Jikumaru, Y.; Kamiya, Y.; Shiharu, K. Imprimantin C1, a novel plant immune-priming compound, function as a partial agonist of salicylic acid. Sci. Rep. 2012, 2, 705. [Google Scholar] [CrossRef] [PubMed]
  145. Kuai, X.; Barraco, C.; Després, C. Combining Fungicides and Prospective NPR1-Based “Just-in-Time” Immunomodulating Chemistries for Crop Protection. Front. Plant Sci. 2017, 8, 1715. [Google Scholar] [CrossRef] [PubMed]
Table 1. β-Aminobutyric acid and used pathosystems.
Table 1. β-Aminobutyric acid and used pathosystems.
Chemical NameChemical StructurePlant/Pathogen Interaction Laboratory/Field Experiments)Reference
β-Aminobutyric acid Agronomy 08 00005 i001Arabidopsis/hyaloperonospora parasitica, Botrytis cinerea (Laboratory)[46]
Brassica napus/Leptosphaeria maculans (Laboratory)[49]
Lettuce/Bremia lactucae (Laboratory)[47]
Tomato/Phytophthora infestans (Laboratory)[48]
Potato/Phytophthora infestans (Laboratory/Field)[51,52]
Grapevine/Plasmopara viticola[50]
Table 2. Salicylate and benzoate derivatives and used pathosystems.
Table 2. Salicylate and benzoate derivatives and used pathosystems.
Chemical/Trade NameChemical StructurePlant/Pathogen Interaction Laboratory/Field Experiments)Reference
3-chlorosalicylic acid,
4-chlorosalicylic acid,
5-chlorosalicylic acid,
3,5-dichlorsalicylic acid
Agronomy 08 00005 i002Tobacco/TMV (Laboratory)[55]
3-fluorosalicylic acid,
5-fluorosalicylic acid
Agronomy 08 00005 i003Tobacco/TMV (Laboratory)[56]
2-(3,4-dihydroxy-6-(hydroxymethyl)-5-(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)thio)benzohydrazide: SA glucoconjugate hydrazine Agronomy 08 00005 i004Cucumber/Colletotrichum orbiculare, Fusarium oxysporum, Ralstonia solani, Phytophthora capsici (Laboratory)[57]
3-chlorobenzoic acid,
3,5-dichlorobenzoic acid
Agronomy 08 00005 i005Arabidopsis/Hyaloperonospora parasitica, Pseudomonas syringae (Laboratory)[54]
Para amino benzoic acid Agronomy 08 00005 i006Pepper/CMV, Xanthomonas axonopodis pv. Vesicatoria (Laboratory)[58]
Table 3. Nicotinic acid derivatives and used pathosystems.
Table 3. Nicotinic acid derivatives and used pathosystems.
Chemical/Common or Trade NameChemical StructurePlant/Pathogen Interaction (Laboratory/Field Experiments)Reference
2,6-dichloro-isonicotinic acid (INA)(CGA41396), CGA41397 Agronomy 08 00005 i007Tobacco/TMV, Cercospora nicotiana, Peronospora tabacina (Laboratory)
Cucumber/Colletotrichum lagenarium Sphaerotheca fuliginea (Laboratory)
Bean/Uromyces appendiculatus (Laboratory)
N-cyanomethyl-2-chloro isonicotinic acid (NCI) Agronomy 08 00005 i008Tobacco/Tobacco mosaic virus, Oidium lycopersici, Pseudomans syringae pv. tabaci (Laboratory)
Rice/Xanthomonas oryzae pv. oryzae, Magnatoporthe grisea (Field)
Table 4. Pyrazole, thiazole, and thiadiazole derivatives and used pathosystems.
Table 4. Pyrazole, thiazole, and thiadiazole derivatives and used pathosystems.
Chemical/Trade NameChemical StructurePlant/Pathogen Interaction (Laboratory/Field Experiments)Reference
3-chloro-1-methyl-1H-pyrazole-5-carboxylic acid (CMPA) Agronomy 08 00005 i009Tobacco/Pseudomonas syringae pv. tabaci, Oidium sp. (Laboratory)[72,74]
Rice/Xanthomonas oryzae pv. Oryzae (Field)[73]
3-allyloxy-1,2-benzithiazole1-1-dioxide (Probenazole, PBZ/Oryzemate®) Agronomy 08 00005 i010Rice/Magnaporthe oryzae (Field)[70]
1,2-benzisothiazolin-3-one-1,1-dioxide (BIT, Saccharin) Agronomy 08 00005 i011Tobacco/TMV (Laboratory)
Rice/Magnaporthe grisea, Xanthomonas oryzae pv. Oryzae (Field)
Barley/Blumeria graminis f. sp. Hordei (Laboratory)
Cucumber/Colletotrichum lagenarium
Bean/Uromyces faba (Laboratory)
Soybean/Phakospora pachirhizi (Laboratory)
3,4-dichloro-2′-cyano-1,2-thiazole-5-carboxanilide Isothianil (Isotianil/Stout®) Agronomy 08 00005 i012Rice/Xanthomonas oryzae pv. oryzae, Magnaporthe grisea (Field)
Wheat/Blumeria graminis f. sp. Tritici (Laboratory) Cucumber/Colletotrichum orbiculare, Xanthomonas campestris pv. Cucurbitae (Laboratory)
Chinese cabbage/Alternaria brassicae (Laboratory)
Pumpkin/Sphaerotheca fuliginea (Laboratory)
Strawberry/Colletotrichum acutatum (Laboratory)
Peach/Xanthomonas campestris pv. Pruni (Laboratory)
Benzo-1,2,3-thiadiazole-7-carbothionic acibenzolar-S-methyl ester (BTH/Bion®/Actigrad®) Agronomy 08 00005 i013Apple/Erwinia amylovora (Field)[82]
Citrus/Xanthomonas citri, Xanthomonas axonopodis pv. Citrucula (Field)[83]
Rape/Pseudomonas syrngae pv. maculicola, leptosphaera maculans (Laboratory)[84]
Japanese pear/Venturia nashicola (Laboratory)[85]
Cowpea/Colletotrichum destructivum (Laboratory)[86]
Tobacco/TMV, CMV, Tomato spotted wilt virus (Laboratory)[87,88]
Cucumber/Colletotrichum orbiculare, CMV (Laboratory)[85,89]
Tomato/Clavibacter michighanensis subs. michiganensis, Verticillium dahliae (Laboratory/Field)[90,91]
Oil seed rape/Leptosphaeria maculans (Laboratory/Field)[92]
2,2-2trifluoroethylbenzo(d) (1,2,3) thiadiazole-7-carboxylatic acid Agronomy 08 00005 i014Cucumber/Erysiphae cichoracearum, Colletotrichum lagenarium (Field)[93]
N-(3-Chloro-4-Methylphenyl)-4-Methyl-1,2,3-thiadiazole-5-Carboxamide Tiadinil (TDL, V-GET®) Agronomy 08 00005 i015Rice/Magnoporthe grisea (Field)[80]
Tobacco/Tobacco mosaic virus, Pseudomonas syringae pv. tabaci, Erysiphae cichoracearum (Laboratory)[66,94]
Tea/Colletotrichum theaasinensis, Pestalotiopsis longista (Field)[95]
2,5-bis (pyridi-2-yl)-1,3,4-thiadiazol Agronomy 08 00005 i016Tomato/Verticillium dahliae (Laboratory)[96]
Bis(μ-2,5-bis(pyridin-2-yl)-1,3,4-thiadiazoleκ4N2,N3:N4,N5)bis(dihydrato-κO)nickel(II)) (NiL2) Agronomy 08 00005 i017Tomato/Verticillium dahliae (Laboratory)[96]
bis(azido-κN)bis(2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole-κ2N2,N3)nickel(II) (NiL2(N3)2) Agronomy 08 00005 i018Tomato/Verticillium dahliae (Laboratory)[97]
Bis((2,5-bis(pyridine-2-yl)-1,3,4-thiadiazole-di-azido copper(II)) (CuLN3)2 Agronomy 08 00005 i019Tomato/Verticillium dahliae, Agrobacterium tumefaciens (Laboratory)[98]
Table 5. Imprimatins as new immune priming compounds.
Table 5. Imprimatins as new immune priming compounds.
Chemical/Trade NameChemical StructurePlant/Pathogen InteractionReference
2-((E)-2-(2-bromo-4-hydroxy-5-methoxyphenyl)ethenyl) quinolin-8-ol: Imprimatin A1 Agronomy 08 00005 i020Arabidopsis thaliana/Pseudomonas syringae pv. tomato DC3000 avrRp m1[11]
7-chloro-2-((E)-2- (4-nitrophenyl)ethenyl)-4H-3,1-benzoxazin-4-one: Imprimatin A2 Agronomy 08 00005 i021Arabidopsis thaliana/Pseudomonas syringae pv. tomato DC3000 avrRp m1
4-((E)-2-(quinolin-2-yl)ethenyl)phenol: Imprimatin A3 Agronomy 08 00005 i022Arabidopsis thaliana/Pseudomonas syringae pv. tomato DC3000 avrRp m1
2-(3-(2-furyl)-3-phenylpropyl)benzo(c)azoline-1,3-dione: Imprimatin B1 Agronomy 08 00005 i023Arabidopsis thaliana/Pseudomonas syringae pv. tomato DC3000 avrRp m1
3-(2-furyl)-3-phenylpropylamine: Imprimatin B2 Agronomy 08 00005 i024Arabidopsis thaliana/Pseudomonas syringae pv. tomato DC3000 avrRp m1
((E)-(1-amino-2-(2-oxopyrrolidin-1-yl)ethylidene)amino) 4-chlorobenzoate: Imprimatin C1 Agronomy 08 00005 i025Arabidopsis thaliana/Pseudomonas syringae pv. tomato DC3000 avrRp m1[144]
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