Search Results (28)

Acteoside (ACT), a prominent compound of the hydroxytyrosol-type phenylethanol glycoside (HPG) class, is present in plants and holds significant potential for food and pharmaceutical applications. However, the limited production of ACT in plants restricts its broader utilization. Although the biosynthetic pathways of ACT are increasingly understood, its transport mechanisms within plants remain unclear. RgMATE6, a vacuolar-type Multidrug and Toxic Compound Extrusion (MATE) transporter identified in Rehmannia glutinosa (a plant known for ACT p roduction), was selected for investigation. This study aims to elucidate the role of RgMATE6 in ACT transport and its impact on ACT biosynthesis. Our study utilized a multidisciplinary approach, including in silico analysis to predict substrate specificity, quantitative real-time PCR (qRT-PCR) to quantify gene expression, HPLC to measure HPG levels, vacuolar membrane vesicle uptake assays to validate RgMATE6 transport activity in vitro, and genetic transformation in R. glutinosa to assess its functional roles in vivo. In silico analysis identified RgMATE6 as a phenolic compound transporter, and correlation analysis revealed a strong positive association between the HPG accumulation and RgMATE6 expression in R. glutinosa. Functional validation through vacuolar membrane vesicle uptake assays in Nicotiana benthamiana confirmed RgMATE6’s role as an HPG transporter, demonstrating a significant preference for ACT. Overexpression and repression experiments in R. glutinosa further demonstrated that RgMATE6 facilitates ACT import into vacuoles and enhances its production. Additionally, tissue-specific expression analysis revealed the coordinated expression patterns between RgMATE6 and six ACT biosynthetic genes in the transgenic plants. RgMATE6 facilitates the transport and accumulation of ACT within vacuoles, and its expression might synergize with ACT biosynthesis. These findings establish a framework for improving ACT and other HPG production through targeted manipulation of plant MATE transporters. Full article

This study aimed to determine the stress mechanisms induced by foliar methyl jasmonate (MeJA) application in Vaccinium corymbosum cultivars subjected to water deficit (WD) and aluminum toxicity (Al). Two V. corymbosum cultivars, Star and Legacy, were subjected to different treatments in an Andisol: control (80% field capacity and low Al saturation), combined WD + Al (50% field capacity and 85% Al saturation), and different concentrations of foliar MeJA application (10 μM, 50 μM, and 100 μM) under WD + Al conditions. The determination of photosynthetic pigments, osmolytes, and organic acids, as well as the auxin levels and the expression of Aluminium-Activated Malate Transporter (ALMT) and Multidrug and Toxic Compound Extrusion (MATE) genes, was analyzed at 7 and 21 days. Foliar MeJA application increased chlorophyll a, b, and carotenoid levels, mainly at 50 µM, exhibiting early Star responses with up to 1.5-fold higher pigment accumulation, and a later increase in Legacy with up to 1.4-fold higher accumulation. Proline increases up to 2.2-fold in roots and sugar by 1.4-fold in leaves of both cultivars. The MeJA application increases the auxin levels by up to 2.3-fold in Star roots at 7 days and by up to 1.4-fold in Legacy leaves at 21 days. MeJA-induced upregulation of ALMT and MATE gene expression facilitated Al detoxification, with malate and citrate levels increasing up to 2-fold. Hierarchical clustering confirmed that the Star cultivar activated resistance mechanisms early, while the Legacy cultivar exhibited delayed but sustained resistance mechanisms. MeJA improves V. corymbosum resistance to combined WD + Al stress by modulating photosynthetic pigments, osmolytes, organic acids, and hormone regulation. This finding underscores the biotechnological potential of MeJA application to improve stress resilience and optimize crop performance under adverse environmental conditions. Full article

Weeds present a pervasive challenge in agricultural fields. The integration of herbicide-resistant crops with chemical weed management offers an effective solution for sustainable weed control while reducing labor inputs, particularly in large-scale intensive farming systems. Consequently, the development of herbicide-resistant cultivars has emerged as an urgent priority. In this study, we found that the G311E mutant gene of Arabidopsis MATE (multidrug and toxic compound extrusion) family transporter DTX6, designated DTX6m, confers robust resistance to bipyridyl herbicides paraquat and diquat in rice. DTX6m-overexpression lines exhibited marked resistance to these two herbicides, tolerating diquat concentrations up to 5 g/L, which is five-fold higher than the recommended field application dosage. Agronomic assessments demonstrated that grain yields of DTX6m-overexpressing plants were statistically equivalent to those of wild-type plants. Moreover, the plants displayed beneficial phenotypic changes, such as accelerated flowering and a slight reduction in height. Seed morphometric analysis indicated that in comparison with the wild-type control, DTX6m-transgenic lines exhibited altered grain dimensions while maintaining consistent 1000-grain weight. Nutritional assays further demonstrated that DTX6m increased the levels of free amino acids in seeds, while normal protein and starch contents were retained. Collectively, these results establish that DTX6m effectively boosts rice resistance to paraquat and diquat, validating DTX6m as a candidate gene for engineering plant herbicide resistance and also implying a potential role for DTX6m in amino acid homeostasis in plants. Full article

Peanut faces yield constraints due to aluminum (Al) toxicity in acidic soils. The multidrug and toxic compound extrusion (MATE) family is known for extruding organic compounds and transporting plant hormones and secondary metabolites. However, the MATE transporter family has not yet been reported in peanuts under the Al stress condition. In this genome-wide study, we identified 111 genes encoding MATE proteins from the cultivated peanut genome via structural analysis, designated as AhMATE1–AhMATE111. Encoded proteins ranged from 258 to 582 aa residues. Based on their phylogenetic relationship and gene structure, they were classified into six distinct groups. Genes were distributed unevenly on twenty peanut chromosomes. Chr-05 exhibited the higher density of 12%, while chr-02 and chr-11 have the lowest 1% of these loci. Peanut MATE genes underwent a periodic strong to moderate purifying selection pressure during evolution, exhibiting both tandem and segmental duplication events. Segmental duplication accounted for 82% of the events, whereas tandem duplication represented 18%, with both events predominantly driving their moderate expansion. Further investigation of seven AhMATE genes expression profiles in peanut root tips resulted in distinct transcriptional responses at 4, 8, 12, and 24 h post-Al treatment. Notably, AhMATE genes exhibited greater transcriptional changes in the Al-tolerant cultivar 99-1507 compared to the Al-sensitive cultivar ZH2 (Zhonghua No.2). Our findings provide the first comprehensive genome-wide analysis of the MATE family in cultivated peanuts, highlighting their potential roles in response to Al stress. Full article

The escalating global health crisis of antibiotic resistance, driven by the rapid emergence of multidrug-resistant (MDR) bacterial pathogens, necessitates urgent and innovative countermeasures. This review comprehensively examines the diverse mechanisms employed by bacteria to evade antibiotic action, including alterations in cell membrane permeability, efflux pump overexpression, biofilm formation, target site modifications, and the enzymatic degradation of antibiotics. Specific focus is given to membrane transport systems such as ATP-binding cassette (ABC) transporters, resistance–nodulation–division (RND) efflux pumps, major facilitator superfamily (MFS) transporters, multidrug and toxic compound extrusion (MATE) systems, small multidrug resistance (SMR) families, and proteobacterial antimicrobial compound efflux (PACE) families. Additionally, the review explores the global burden of MDR pathogens and evaluates emerging therapeutic strategies, including quorum quenching (QQ), probiotics, postbiotics, synbiotics, antimicrobial peptides (AMPs), stem cell applications, immunotherapy, antibacterial photodynamic therapy (aPDT), and bacteriophage. Furthermore, this review discusses novel antimicrobial agents, such as animal-venom-derived compounds and nanobiotics, as promising alternatives to conventional antibiotics. The interplay between clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) in bacterial adaptive immunity is analyzed, revealing opportunities for targeted genetic interventions. By synthesizing current advancements and emerging strategies, this review underscores the necessity of interdisciplinary collaboration among biomedical scientists, researchers, and the pharmaceutical industry to drive the development of novel antibacterial agents. Ultimately, this comprehensive analysis provides a roadmap for future research, emphasizing the urgent need for sustainable and cooperative approaches to combat antibiotic resistance and safeguard global health. Full article

In recent years, membrane transporters have attracted considerable interest regarding their involvement in the molecular dialogue occurring between microbes and their hosts. In particular, the multidrug and toxic compound extrusion (MATE) transporters form a family of integral membrane proteins, mainly involved in the efflux of toxic and xenobiotic compounds. They are present in all living organisms, both prokaryotes and eukaryotes, where they have a wide array of extremely different roles. In plants, MATE proteins are involved in many important physiological processes, such as plant development, as well as the active transport of several secondary metabolites. In microorganisms, they are mainly implicated in the efflux of toxic compounds and thus contribute to drug resistance. Conversely, information about the actual role of MATE transporters in the interaction between plants and microorganisms, including phytopathogens, is still limited, according to the number of publications available on this topic. Indeed, an understanding of their roles in the plant–pathogen interaction could be essential to increase the knowledge of their molecular conversation and to provide data for the design and development of innovative and sustainable anti-infective strategies to control and manage plant pathogens. Full article

The multidrug and toxic compound extrusion (MATE) family is the latest class of novel secondary transporters discovered in plants. However, there is currently no comprehensive analysis of the MATE gene family in the tea plant. In this study, 68 CsMATE genes were identified from the tea plant genome using bioinformatic methods. In general, we analyzed the evolutionary relationships, intron–exon structure, distribution in chromosomes, conserved domains, and gene expression patterns in different tissues and stresses of the CsMATE gene family. The 68 CsMATEs were phylogenetically divided into four major clusters (Class I to Class IV). The CsMATE genes within the same class exhibit similar structural features, while displaying certain distinctions across different classes. Evolutionary analysis indicated that the CsMATE gene family expanded mainly through gene duplication events, in addition to proximal duplication. Through the analysis of cis-acting elements, it was found that CsMATE genes may be involved in the growth, development, and stress response. Furthermore, we observed that certain CsMATE genes could be induced to exhibit expression under abiotic stress conditions such as low temperature, high salinity (NaCl), osmotic stress (PEG), and methyl jasmonate treatment (MeJA). The findings presented herein offer a crucial theoretical foundation for elucidating the biological functions of CsMATE genes, particularly in response to abiotic stress, and furnish valuable potential genetic resources for tea plant resistance breeding. Full article

The Multidrug and Toxic Compound Extrusion (MATE) proteins serve as pivotal transporters responsible for the extrusion of metabolites, thereby playing a significant role in both plant development and the detoxification of toxins. The MATE gene family within the Brachypodium distachyon, which is an important model organism of the Poaceae family, remains largely unexplored. Here, a comprehensive identification and analysis of MATE genes that complement B. distachyon were conducted. The BdMATE genes were systematically categorized into five distinct groups, predicated on an assessment of their phylogenetic affinities and protein structure. Furthermore, our investigation revealed that dispersed duplication has significantly contributed to the expansion of the BdMATE genes, with tandem and segmental duplications showing important roles, suggesting that the MATE genes in Poaceae species have embarked on divergent evolutionary trajectories. Examination of ω values demonstrated that BdMATE genes underwent purifying selection throughout the evolutionary process. Furthermore, collinearity analysis has confirmed a high conservation of MATE genes between B. distachyon and rice. The cis-regulatory elements analysis within BdMATEs promoters, coupled with expression patterns, suggests that BdMATEs play important roles during plant development and in response to phytohormones. Collectively, the findings presented establish a foundational basis for the subsequent detailed characterization of the MATE gene family members in B. distachyon. Full article

Membrane transporters interact not only with endogenous substrates but are also engaged in the transport of xenobiotics, including drugs. While the coordinated function of uptake (solute carrier family—SLC and SLCO) and efflux (ATP-binding cassette family—ABC, multidrug and toxic compound extrusion family—MATE) transporter system allows vectorial drug transport, efflux carriers alone achieve barrier functions. The modulation of transport functions was proved to be effective in the treatment strategies of various pathological states. Sodium–glucose cotransporter-2 (SGLT2) inhibitors are the drugs most widely applied in clinical practice, especially in the treatment of diabetes mellitus and heart failure. Sodium taurocholate co-transporting polypeptide (NTCP) serves as virus particles (HBV/HDV) carrier, and inhibition of its function is applied in the treatment of hepatitis B and hepatitis D by myrcludex B. Inherited cholestatic diseases, such as Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) can be treated by odevixibat and maralixibat, which inhibit activity of apical sodium-dependent bile salt transporter (ASBT). Probenecid can be considered to increase uric acid excretion in the urine mainly via the inhibition of urate transporter 1 (URAT1), and due to pharmacokinetic interactions involving organic anion transporters 1 and 3 (OAT1 and OAT3), it modifies renal excretion of penicillins or ciprofloxacin as well as nephrotoxicity of cidofovir. This review discusses clinically approved drugs that affect membrane/drug transporter function. Full article

Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this compound in hepatocyte suspension and when 18 phase I metabolites and 5 phase II metabolites [i.e., N-dearylation (M6), hydroxylation (M1, M19, M21), dihydroxylation (M7, M8, M14, M22), trihydroxylation (M13, M18), hydroxylation and reduction (M20), dihydroxylation and reduction (M9, M16), hydrolysis (M23), hydroxylation and glucuronidation (M11, M15), hydroxylation and sulfation (M17), dihydroxylation and sulfation (M10, M12), N-dearylation and hydroxylation (M3, M4), N-dearylation and dihydroxylation (M5), and N-dearylation and trihydroxylation (M2)] were identified from JP-1366 incubation with the hepatocytes from humans, mice, rats, dogs, and monkeys. Based on the cytochrome P450 (CYP) screening test and immune-inhibition analysis with CYP antibodies, CYP3A4 and CYP3A5 played major roles in the metabolism of JP-1366 to M1, M3, M4, M6, M8, M9, M13, M14, M16, M18, M19, M21, and M22. CYP1A2, 2C8, 2C9, 2C19, and 2D6 played minor roles in the metabolism of JP-1366. UDP-glucuronosyltransferase (UGT) 2B7 and UGT2B17 were responsible for the glucuronidation of M1 to M15. However, JP-1366 and active metabolite M1 were not substrates for drug transporters such as organic cation transporter (OCT) 1/2, organic anion transporter (OAT) 1/3, organic anion transporting polypeptide (OATP)1B1/1B3, multidrug and toxic compound extrusion (MATE)1/2K, P-glycoprotein (P-gp), and breast cancer-resistant protein (BCRP). Only M1 showed substrate specificity for P-gp. The findings indicated that drug-metabolizing enzymes, particularly CYP3A4/3A5, may have a significant role in determining the pharmacokinetics of zastaprazan while drug transporters may only have a small impact on the absorption, distribution, and excretion of this compound. Full article

Plipastatin, an antimicrobial peptide produced by Bacillus subtilis, exhibits remarkable antimicrobial activity against a diverse range of pathogenic bacteria and fungi. However, the practical application of plipastatin has been significantly hampered by its low yield in wild Bacillus species. Here, the native promoters of both the plipastatin operon and the sfp gene in the mono-producing strain M-24 were replaced by the constitutive promoter P₄₃, resulting in plipastatin titers being increased by 27% (607 mg/mL) and 50% (717 mg/mL), respectively. Overexpression of long chain fatty acid coenzyme A ligase (LCFA) increased the yield of plipastatin by 105% (980 mg/mL). A new efflux transporter, YoeA, was identified as a MATE (multidrug and toxic compound extrusion) family member, overexpression of yoeA enhanced plipastatin production to 1233 mg/mL, an increase of 157%, and knockout of yoeA decreased plipastatin production by 70%; in contrast, overexpression or knockout of yoeA in mono-producing surfactin and iturin engineered strains only slightly affected their production, demonstrating that YoeA acts as the major exporter for plipastatin. Co-overexpression of lcfA and yoeA improved plipastatin production to 1890 mg/mL, which was further elevated to 2060 mg/mL after abrB gene deletion. Lastly, the use of optimized culture medium achieved 2514 mg/mL plipastatin production, which was 5.26-fold higher than that of the initial strain. These results suggest that multiple strain engineering is an effective strategy for increasing lipopeptide production, and identification of the novel transport efflux protein YoeA provides new insights into the regulation and industrial application of plipastatin. Full article

Demethylation inhibitors (DMIs), including prochloraz, are popular fungicides to control citrus postharvest pathogens such as Penicillium digitatum (green mold). However, many P. digitatum strains have developed prochloraz resistance, which decreases drug efficacy. Specific major facilitator superfamily (MFS) transporter gene mfs2, encoding drug-efflux pump protein MFS2, has been identified in P. digitatum strain F6 (PdF6) to confer fungal strain prochloraz resistance. However, except for the drug-efflux pump function of MFS2, other mechanisms relating to the Pdmfs2 are not fully clear. The present study reported a transcriptome investigation on the mfs2-defective P. digitatum strain. Comparing to the wild-type strain, the mfs2-defective strain showed 717 differentially expressed genes (DEGs) without prochloraz induction, and 1221 DEGs with prochloraz induction. The obtained DEGs included multiple isoforms of MFS transporter-encoding genes, ATP-binding cassette (ABC) transporter-encoding genes, and multidrug and toxic compound extrusion (MATE) family protein-encoding genes. Many of these putative drug-efflux pump protein-encoding genes had significantly lower transcript abundances in the mfs2-defective P. digitatum strain at prochloraz induction, as compared to the wild-type strain, including twenty-two MFS transporter-encoding genes (MFS1 to MFS22), two ABC transporter-encoding genes (ABC1 and ABC2), and three MATE protein-encoding genes (MATE1 to MATE3). The prochloraz induction on special drug-efflux pump protein genes in the wild-type strain was not observed in the mfs2-defective strain, including MFS21, MFS22, ABC2, MATE1, MATE2, and MATE3. On the other hand, the up-regulation of other drug-efflux pump protein genes in the mfs2-defective strain cannot recover the fungal prochloraz resistance, including MFS23, MFS26, MFS27, MFS31, MFS33, and ABC3 to ABC8. The functional enrichment of DEGs based on Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and euKaryotic Orthologous Groups (KOG) database resources suggested some essential contributors to the mfs2-relating prochloraz resistance, including ribosome biosynthesis-related genes, oxidative phosphorylation genes, steroid biosynthesis-related genes, fatty acid and lipid metabolism-related genes, and carbon- and nitrogen-metabolism-related genes. The results indicated that the MFS2 transporter might be involved in the regulation of multiple drug-efflux pump protein gene expressions and multiple metabolism-related gene expressions, thus playing an important role in developing P. digitatum prochloraz resistance. Full article

The multidrug and toxic compound extrusion (MATE) proteins are coding by a secondary transporter gene family, and have been identified to participate in the modulation of organic acid exudation for aluminum (Al) resistance. The soybean variety Glycine max “Tamba” (TBS) exhibits high Al tolerance. The expression patterns of MATE genes in response to Al stress in TBS and their specific functions in the context of Al stress remain elusive. In this study, 124 MATE genes were identified from the soybean genome. The RNA-Seq results revealed significant upregulation of GmMATE13 and GmMATE75 in TBS upon exposure to high-dose Al³⁺ treatment and both genes demonstrated sequence homology to citrate transporters of other plants. Subcellular localization showed that both proteins were located in the cell membrane. Transgenic complementation experiments of Arabidopsis mutants, atmate, with GmMATE13 or GmMATE75 genes enhanced the Al tolerance of the plant due to citrate secretion. Taken together, this study identified GmMATE13 and GmMATE75 as citrate transporter genes in TBS, which could improve citrate secretion and enhance Al tolerance. Our findings provide genetic resources for the development of plant varieties that are resistant to Al toxicity. Full article

Multidrug and toxic compound extrusion (MATE) transporters are ancient proteins conserved among various kingdoms, from prokaryotes to eukaryotes. In plants, MATEs usually form a large family in the genome. Homologous MATE transporters have different subcellular localizations, substrate specificities, and responses to external stimuli for functional differentiations. The substrates of MATEs in plants include polyphenols, alkaloids, phytohormones, and ion chelators. The accumulation of these substrates is often associated with favorable agronomic traits such as seed and fruit colors, the balance between dormancy and germination, taste, and stress adaptability. In crops, wild germplasms and domesticated germplasms usually have contrasting agronomic traits such as seed color, seed taste, and stress tolerance. MATE transporters are involved in the regulations of these traits. In this review, we discuss the uniqueness and significance of there being such a large family of MATEs in plants, their substrate diversity that enables them to be involved in various agronomic traits, and the allelic forms and the expression patterns of MATE that are associated with favorable agronomic traits in domesticated crops. The understanding on the roles of MATEs in regulating favorable agronomic traits in crops will provide hints for the selection of genes for molecular breeding that improve desirable traits. Full article

In plants, the translocation of molecules, such as ions, metabolites, and hormones, between different subcellular compartments or different cells is achieved by transmembrane transporters, which play important roles in growth, development, and adaptation to the environment. To facilitate transport in a specific direction, active transporters that can translocate their substrates against the concentration gradient are needed. Examples of major active transporters in plants include ATP-binding cassette (ABC) transporters, multidrug and toxic compound extrusion (MATE) transporters, monosaccharide transporters (MSTs), sucrose transporters (SUTs), and amino acid transporters. Transport via ABC transporters is driven by ATP. The electrochemical gradient across the membrane energizes these secondary transporters. The pH in each cell and subcellular compartment is tightly regulated and yet highly dynamic, especially when under stress. Here, the effects of cellular and subcellular pH on the activities of ABC transporters, MATE transporters, MSTs, SUTs, and amino acid transporters will be discussed to enhance our understanding of their mechanics. The relation of the altered transporter activities to various biological processes of plants will also be addressed. Although most molecular transport research has focused on the substrate, the role of protons, the tiny counterparts of the substrate, should also not be ignored. Full article