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Review

Threat and Control of tet(X)-Mediated Tigecycline-Resistant Acinetobacter sp. Bacteria

by
Chong Chen
1,2,*,
Taotao Wu
1,2,
Jing Liu
1,2 and
Jie Gao
1,2
1
Joint International Research Laboratory of Agriculture and Agri-Product Safety, Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China
2
College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009, China
*
Author to whom correspondence should be addressed.
Foods 2025, 14(19), 3374; https://doi.org/10.3390/foods14193374
Submission received: 7 September 2025 / Revised: 27 September 2025 / Accepted: 28 September 2025 / Published: 29 September 2025
(This article belongs to the Special Issue Strategies for Controlling Pathogenic Microbial Contamination in Animal-Derived Food Products: An Antimicrobial Approach)
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Abstract

Tigecycline is regarded as one of the last-resort antibiotics against multidrug-resistant (MDR) Acinetobacter sp. bacteria. Recently, the tigecycline-resistant Acinetobacter sp. isolates mediated by tet(X) genes have emerged as a class of global pathogens for humans and food-producing animals. However, the genetic diversities and treatment options were not systematically discussed in the era of One Health. In this review, we provide a detailed illustration of the evolution route, distribution characteristics, horizontal transmission, and rapid detection of tet(X) genes in diverse Acinetobacter species. We also detail the application of chemical drugs, plant extracts, phages, antimicrobial peptides (AMPs), and CRISPR-Cas technologies for controlling tet(X)-positive Acinetobacter sp. pathogens. Despite excellent activities, the antibacterial spectrum and application safety need further evaluation and resolution. It is noted that deep learning is a promising approach to identify more potent antimicrobial compounds.

1. Introduction

The genus Acinetobacter is a complicated group of Gram-negative bacteria from multiple sources, such as human, animal, meat, vegetable, fruit, milk, soil, water, activated sludge, and sewage [1,2,3,4,5]. To date, 87 non-duplicate Acinetobacter species have been validly reported (https://www.bacterio.net/genus/acinetobacter, accessed on 6 September 2025). Some of them are well-known opportunistic pathogens for humans and animals, and the most common species is Acinetobacter baumannii, followed by Acinetobacter calcoaceticus, Acinetobacter lwoffii, Acinetobacter pittii, and Acinetobacter junii [6,7,8]. It is estimated that the global incidence of Acinetobacter infections reaches one million cases per year, including ventilator-associated pneumonia, bloodstream infections, and surgical site infections, of which the highest density of infections occurs in intensive care units [6,9]. By contrast, the incidence rate in China and United Arab Emirates is much higher than those reported in the United States and Europe [10,11,12,13]. In addition, the percentage of bloodstream infections in India, Saudi Arabia, and South Africa ranges from 12.4% to 21.3%, with the mortality exceeding 60% [10,14,15,16]. Worrisomely, they are capable of acquiring or up-regulating genetic determinants to develop multidrug resistance, especially the reported resistance to carbapenem and colistin immediately after their clinical application [11,17,18,19]. In 2019, there were 50,000–100,000 deaths caused by carbapenem-resistant A. baumannii (CRAb) around the world [20]. Thereafter, CRAb was classified into the critical group by World Health Organization Bacterial Priority Pathogens List in 2024 [21]. The rapid dissemination of MDR Acinetobacter sp. pathogens renders tigecycline as one of the last options for their clinical infections.
Tigecycline was first approved by the United States Food and Drug Administration (USFDA) in 2005 and imported into Europe in 2006 as well as China in 2011, which belongs to the third-generation tetracycline [22]. It exhibits a broader-spectrum antibacterial activity than the first- and second-generation tetracyclines by inhibiting bacterial protein synthesis [23]. Unfortunately, the minimum inhibitory concentration (MIC) of tigecycline against A. baumannii in Asia was increased when compared with those of Europe and North America [24], of which tigecycline resistance was sporadically detected in 1.7% of clinical Acinetobacter sp. strains in China (https://www.chinets.com/Data/AntibioticDrugFast, accessed on 6 September 2025). The main mechanisms contain efflux pumps [e.g., adeABC and tet(Y)], altered outer membrane permeability (e.g., plsC), altered tigecycline targets of action (e.g., rpsJ), tigecycline-inactivating enzymes [e.g., tet(X)], and DNA repair pathways (e.g., recA) [25,26,27,28]. Since 2019, the tigecycline resistance mediated by tet(X3), tet(X4), tet(X5), tet(X6), tet(X7), and tet(X15) variants has been reported in global Acinetobacter species, especially blaNDM-1-positive strains in food-producing animals [22,29,30,31,32,33,34]. Nevertheless, genetic diversities and how to prevent the threat of tet(X)-positive Acinetobacter spp. remain poorly understood. Herein, we intend to explore their tet(X) evolution, epidemiology, horizontal transmission, detection, and treatment options.

2. Evolution of tet(X)-Mediated Tigecycline Resistance

2.1. Emergence of tet(X) Genes

The tet(X) gene was first described as *Tcr on an R plasmid and formally named on two transposons Tn4351 and Tn4400 in obligate anaerobe Bacteroides fragilis [35,36]. It encodes a flavin-dependent monooxygenase Tet(X), which can degrade tetracycline antibiotics by hydroxylation at C11a and requires flavin adenine dinucleotide (FAD), reduced nicotinamide adenine dinucleotide phosphate (NADPH), molecular oxygen, and Mg2+ for activity (Figure 1) [37]. Tigecycline was also identified as one of the reaction substrates but failed to reach the USFDA tigecycline resistance breakpoint [30,38]. Then, tet(X1) and tet(X2) were reported on a transposon CTnDOT of obligate anaerobe Bacteroides thetaiotaomicron [39]. The Tet(X1) protein encoded by tet(X1) loses its degradation activity due to the lack of 29 amino acids at the N-terminal domain, while the Tet(X2) protein encoded by tet(X2) has a similar degradation activity to the first-reported Tet(X) protein [37]. In recent years, there has been an increasing number of novel tet(X) variants in the genus Acinetobacter, such as tet(X3), tet(X4), tet(X5), tet(X6), tet(X7), and tet(X15), which confer high-level cross-resistance to tigecycline, eravacycline and omadacycline [29,30,31,34,40].

2.2. Structural Insights into Tet(X) Proteins

Phylogenetically, tet(X) homologs may have originated from chromosomal monooxygenase genes in Weeksellaceae (formerly Flavobacteriaceae) bacteria, such as Weeksella spp., Chryseobacterium spp., Elizabethkingia spp., Riemerella spp., and Empedobacter spp. [30,41,42]. All Tet(X) proteins share an overall analogous architecture consisting of the substrate-binding domain, FAD-binding domain, and C-terminal α-helix [30]. The amino acid substitutions at L282, V329, A339, D340, V350, and K351 of Tet(X2) significantly enhance the enzymic degradation activity [40,43]. These substitutions do not directly participate in the binding of tetracyclines and FAD but alter the conformational dynamics of Tet(X) variants through interactions with adjacent amino acid residues [40]. With extensive usage of tetracyclines, the rapid emergence of tet(X) variants possibly promote the adaptation of Acinetobacter species under antibiotic selection pressure [44]. More researchers are needed to develop novel antimicrobial compounds targeting the six sites for preventing tet(X)-positive Acinetobacter sp. pathogens.

3. Global Epidemiology of tet(X)-Positive Acinetobacter sp. Strains

3.1. Classification of tet(X) Genes

In total, there are 17 non-redundant tet(X) variants reported in Acinetobacter app. in eight countries [30,34,45]. These genes include tet(X2), tet(X3), tet(X3.3)-tet(X3.9), tet(X4), tet(X5), tet(X5.4), tet(X6), tet(X6) variant, tet(X7), tet(X13) variant, and tet(X15), with lengths ranging from 1137 bp to 1167 bp (Figure 2). Apparently, three pairs of genes are named repeatedly among them. By multiple sequence alignment of complete nucleotide sequences, tet(X2) (AJ311171) and tet(X10) (KU548536) share a 100% nucleotide identity; tet(X6) (MN507533) and tet(X5.2) (CP048670) share a 100% nucleotide identity; and one tet(X6) variant (CP048828) and tet(X5.3) (CP048661) share a 100% nucleotide identity (Figure 2).

3.2. China

Statistically, the tet(X)-positive Acinetobacter sp. strains have been reported in sixteen provinces in China, of which Zhejiang, Guangdong, and Jiangsu provinces covered the majority (>50 isolates per province; Figure 3). By bacterial taxonomy, these strains were widely distributed in 12 different Acinetobacter species except the undefined ones (Figure 4). Details are as follows.

3.2.1. Predominate Groups of tet(X3) and tet(X6)

Since the first report of tet(X3) in A. baumannii, it has been detected across at least 11 Acinetobacter species in 12 provinces of China (Figure 3 and Figure 4) [29,30,46]. Whole genome sequencing (WGS) indicated that tet(X3) was the major subtype in Acinetobacter spp. (Figure 4), most of which were Acinetobacter indicus isolates from animals and neighboring environments [30]. Sporadically, two Acinetobacter gandensis strains and one novel Acinetobacer species carrying tet(X3) were detected in vegetables in Jiangsu and Zhejiang provinces [30]. It is noted that the tet(X3) and blaNDM-1 genes were simultaneously detected in A. indicus, Acinetobacter schindleri, and A. lwoffii [29,30,33]. One study also identified seven novel tet(X3) variants [namely tet(X3.3)–tet(X3.9)] from pig-derived Acinetobacter variabilis and chicken-derived A. schindleri in Guangxi province, among which only tet(X3.7) and tet(X3.9) were capable of encoding a functional protein [47]. The tet(X6) gene [namely tet(X5.2)] was first reported in pig-derived Proteus genomospecies 6 in Henan province [48]. To date, it has been detected among at least eight Acinetobacter species in 12 provinces in China (Figure 3 and Figure 4), especially with tet(X3) in vegetable-derived A. gandensis [22,30,49,50,51]. A novel variant of tet(X6) [namely tet(X5.3)] was reported in Acinetobacter piscicola and blaNDM-1-positive A. baumannii from chicken, pig, and soil in Guangdong and Zhejiang provinces [30,52].

3.2.2. Sporadic Groups of tet(X2), tet(X4), tet(X5), and tet(X15)

Since the discovery of tet(X2) [namely tet(X10)] in B. thetaiotaomicron, only one human strain of A. pittii carrying chromosome-borne tet(X2) was isolated in Zhejiang province [39,53]. Since discovering tet(X4) in Escherichia coli in 2019, a tet(X4)-positive A. baumannii strain was isolated from inpatients in Jilin province, followed by five tet(X4)-positive A. indicus strains from migratory birds in Qinghai province [29,30]. An Acinetobacter towneri strain carrying chromosome-borne tet(X4) was also detected in pig-derived samples in Henan province [54]. The tet(X5) gene was first reported in a human-derived A. baumannii strain in Hebei province [55]. Subsequently, it was isolated in five duck- and three chicken-derived A. baumannii strains in Guangdong province [22]. A novel variant, tet(X5.4), was isolated in a pig-derived A. indicus strain in Guangxi province [49]. For tet(X15), only one chicken strain of A. variabilis carrying chromosome-borne tet(X15) was discovered in Jiangsu province [31].

3.3. Other Countries

The detection of tet(X)-positive Acinetobacter spp. is relatively rare in seven other countries. Briefly, one tigecycline- and carbapenem-resistant A. towneri isolate co-harboring plasmid-mediated tet(X7) and blaNDM-1 was reported in hospital wastewater in Philippines [34]. Based on a source tracking study of global metagenomic data, tet(X3), tet(X6), and one tet(X13) variant were detected in 12 Acinetobacter sp. strains of human, pig, and cattle origin from Thailand (n = 3), Germany (n = 3), Ireland (n = 3), Pakistan (n = 1), Peru (n = 1), and Cote d’Ivoire (n = 1), but the degradation activity, genetic environment, and Acinetobacter subspecies of the tet(X13) variant need further identification [45]. It is noted that the limited epidemiological studies may underestimate the prevalence and transmission risk of Acinetobacter spp. in various countries, which could be optimized by WGS techniques.

4. Horizontal Transmission of tet(X) Genes

4.1. Mobilizable Plasmids

So far, the plasmid-mediated tet(X3), tet(X3.7), tet(X3.8), tet(X3.9), tet(X5), tet(X5.3), tet(X5.4), tet(X6), and tet(X7) genes have been reported in diverse Acinetobacter species [30,34,47,49,55]. According to multiple sequence alignment of plasmid replicons, these Acinetobacter plasmids harboring tet(X) genes were mainly classified into six categories, including GR26, GR31, GR41, GR59, GR60, and GR61 [56]. In vitro conjugation studies showed that the plasmid-mediated horizontal transfer event of tet(X) genes rarely occurred. Only a few strains can be transferred into the recipient Acinetobacter baylyi and A. baumannii strains, with an efficiency of about 10−10–10−6, and imposed significant fitness costs on bacterial growth rates [29,30,47,49,56]. Our previous study confirmed the tet(X)-carrying Acinetobacter plasmids were complex and only 21.7% of them carried conjugation transfer genes [56]. Consequently, the impaired mobility of plasmid-mediated tet(X) genes may be associated with the absence of plasmid conjugation transfer elements, and the specific mechanism warrants more exploration.

4.2. ISCR2-Mediated Transposons

ISCR2, an insertion sequence (IS) related to the IS91 family, is considered atypical because it lacks conventional terminal inverted repeats and does not generate target site duplications upon insertion [57]. It is hypothesized to mediate the horizontal spread of antibiotic resistance genes (e.g., floR and sul2) through a ‘rolling circle’ replication process initiated at oriIS and terminated at non-specific terIS [57]. Except for ISAba1-mediated tet(X2), IS26-mediated tet(X7), and ISAba1-mediated tet(X15), tet(X3), tet(X4), tet(X5), tet(X6), and their variants are also closely related to ISCR2 in Acinetobacter species, with a transposition efficiency of about 10−8–10−6 into the recipient A. baylyi and E. coli strains [22,30,31,34,53]. Namely, the typical genetic environment of tet(X3) is ISCR2-tpnF-tet(X3)-hp-hp-ISCR2, and the upstream ISCR2 is often truncated by IS26 and ISAba14 [30]; the tet(X4) gene has a highly similar genetic environment, namely ISCR2-catD-tet(X4)-ISCR2, across Acinetobacter species, E. coli, Klebsiella pneumoniae, and other Enterobacteriaceae bacteria [30]; the genetic environment of tet(X5) is ISCR2-tpnF-tet(X5)-hp-hp-ISCR2 [30]; the tet(X6) gene has a similar genetic environment between Acinetobacter spp. and Proteus spp., and its basic structure is ISCR2-hp-tet(X6)-hp-ISCR2 [22]. Therefore, ISCR2 can serve as a potential knockout target to inhibit the horizontal spread of tet(X) genes across different bacterial species.

5. Rapid Detection Methods of tet(X) Variants

With the expanding family of tet(X) variants in Acinetobacter spp., there is an urgent demand for rapid detection methods to monitor and prevent tet(X)-mediated cross-resistance to tetracyclines. Firstly, the specific primers of tet(X2), tet(X3), tet(X4), and tet(X5) were successfully designed, and multiplex PCR and multiplex Real-Time PCR assays were developed for screening the tet(X) genes in animal, clinical, and environmental samples [58,59]. Based on visual orange to green (OTG) dye, a loop-mediated isothermal amplification assay was applied to simultaneously detect tet(X2), tet(X3), tet(X4), and tet(X5), which was significantly more sensitive than usual PCR [60]. Coupled with pH-sensitive bromocresol purple, a rapid detection method was also established based on the degradation of eravacycline by Tet(X3)- or Tet(X4)-producing strains, which resulted in reduced eravacycline activity against an acid-producing thermophile Bacillus stearothermophilus indicator strain [61]. An one-tube RPA-CRISPR-Cas12b-based detection system was also developed for specific detection of tet(X4) within 40 min [62]. In addition, MALDITet(X) and MALDITet(X)-plus tests of tigecycline and oxytetracycline were conducted using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for rapid detection of Tet(X)-producing Gram-negative bacteria such as Acinetobacter sp. strains [63,64]. The evolution of novel tet(X) variants and low gene abundance necessitate continuous method updates to maintain detection coverage and accuracy, especially in the field of food-related microbiological detection.

6. Treatment Options

6.1. Chemical Drugs

There has been no novel antibiotic chemical class with activity against A. baumannii that reached patients in over 50 years [65]. In 2024, a novel antibiotic class, tethered macrocyclic peptide (MCP), was reported for the effective treatment of tigecycline-resistant A. baumannii infections [65]. A clinical candidate, zosurabalpin (RG6006), was derived from the MCP class and significantly inhibited highly antibiotic-resistant A. baumannii isolates in vitro and in vivo [65]. A 90% MIC indicated zosurabalpin (1 mg/L) was much lower than those of tigecycline (8 mg/L), colistin (>16 mg/L), and meropenem (>16 mg/L) [65]. Molecular mechanisms revealed it blocked the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane by inhibition of the LptB2FGC complex in Acinetobacter sp. strains [65,66]. As inhibitors of the membrane lipooligosaccharide transporter MsbA, cerastecins were significantly bactericidal in vitro and in murine models of bloodstream or pulmonary A. baumannii infection [67]. Four USFDA-approved drugs, including ZINC000003801919, DB01203, DB11217 and ZINC0000000056652, were identified as efficient inhibitors to combat tigecycline-resistant A. baumannii by targeting the BaeR protein [68]. Doxycycline showed a synergistic effect with benzydamine on tet(X6)-mediated tigecycline-resistant A. baumannii [69]. Toward extended library synthesis of enzymic inhibitors, anhydrotetracycline and semisynthetic analogues were confirmed as competitive inhibitors of Tet(X) enzymes that rescued the activity of tetracyclines against tigecycline-resistant Acinetobacter species [70,71,72].
Deep learning approaches increase the probability of discovering novel chemical drugs (Figure 5). As early as 2020, a broad-spectrum antibiotic, halicin, was discovered through deep learning [73]. The MIC of halicin against clinical MDR A. baumannii 288 was 1 mg/L and the bacterial load in a halicin-treated murine wound model was significantly decreased than that of the vehicle control group [73]. A narrow-spectrum antibiotic against A. baumannii, abaucin, was also screened by deep learning and could overcome intrinsic and acquired resistance mechanisms in clinical isolates [74]. It perturbed lipoprotein trafficking via LolE, which is a functionally conserved protein that contributes to shuttling lipoproteins from the inner membrane to the outer membrane [74]. The bacterial load and inflammation in the A. baumannii-infected mice treated with abaucin were significantly less than those of the vehicle control group [74]. These studies highlight the utility of deep learning approaches to expand our antibiotic arsenal through the discovery of structurally distinct antibacterial molecules.

6.2. Plant Extracts

Plant extracts are a class of natural antimicrobials present in various plants (Figure 5). As a naphthoquinone compound, plumbagin was confirmed as a broad-spectrum inhibitor of Tet(X) enzymes by binding to their catalytic pockets and showed a synergistic bactericidal effect with tetracyclines on tet(X3)- or tet(X4)-mediated tigecycline-resistant strains [75]. Berberine hydrochloride was one of the most common forms of Berberine in Huanglian, and both Berberine hydrochloride and Berberine can restore the antibiotic susceptibility of MDR A. baumannii to tigecycline, meropenem, ciprofloxacin, and sulbactam [76,77]. Baicalein extracted from Scutellaria baicalensis also exhibited a synergistic activity with tigecycline, doxycycline, minocycline, or meropenem against clinical A. baumannii isolates [78,79]. Plant extracts provide a novel treatment option for tigecycline-resistant pathogens, but issues such as concentration dependence and therapeutic safety need to be addressed.

6.3. Phages

Phage is a class of viruses specifically infecting bacteria (Figure 5). With the rapid increase in antibiotic usage and antibiotic resistance, phage therapy is highly anticipated for treating MDR Acinetobacter infections [80,81]. Promisingly, a novel lytic phage, vABWU2101, demonstrated a good antibacterial activity against MDR A. baumannii and biofilms, especially with tigecycline [82]. Phage Abp1 was effective in lysing pan-drug resistant A. baumannii and showed no toxicity on HeLa and THP-1 cells [83]. In a mouse model of wound infection with A. baumannii, wound healing was accelerated when phage Abp1 was given locally [83]. In a systemic infection model, the survival rate of mice treated with phage Abp1 was 100%, and mice livers and kidneys were essentially free of bacteria [83]. Phage cocktail, which combines multiple phages into a cocktail, can overcome the narrow host range [84]. In Europe, a four-phage cocktail composed of Highwayman, Silvergun, Fanak, and PhT2-v2 was effective against the most prevalent ST2-KL3 A. baumannii lineage in Galleria mellonella and mouse models [84]. The survival rate of cocktail-treated mice with phage PBAB08, phage PBAB25, and other phages was increased by 2.3-fold in a mouse model of nasal infection with MDR A. baumannii [85].
Despite some achievements in phage therapy under experimental conditions, only one phage completed a clinical double-blind and randomized study of A. baumannii infections in Phase I/IIa registered on ClinicalTrials.gov (https://clinicaltrials.gov/, accessed on 23 September 2025). On one hand, the deficiencies of host range and standardization of quality evaluation and large-scale production challenge the clinical application of phage therapy [81]. For application risk and public safety, phage resistance has been discovered in recent years [86]. Meanwhile, the phage-mediated antibiotic resistance in Acinetobacter sp. bacteria cannot be ignored, especially colistin resistance and carbapenem resistance of global concern [87,88].

6.4. AMPs

Most AMPs have a composition of less than 100 amino acids and are non-specifically antibacterial by disrupting bacterial membrane [89,90]. A bacterial toxin CcdB-derived peptide, CP1-WT, showed high therapeutic efficacy in treating tigecycline-resistant A. baumannii infection [91]. OH-CATH30 and D-OH-CATH30 derived from King Cobra exhibited good antimicrobial activities against clinical Acinetobacter sp. isolates [92]. Tilapia piscidin 2 (TP2)-based AMPs, TP2-5 and TP2-6, significantly inhibited A. baumannii biofilms with low toxicity even after a consecutive passage [93]. A computational peptide omega76 was designed to combat tigecycline-resistant A. baumannii infection in mice without chronic toxicity [94]. Additionally, machine learning predicted nearly 1 million novel AMPs in the global microbiome, of which 79 out of 100 tested peptides were active in vitro [95]. Two days post-infection of A. baumannii in mice, lachnospirin-1, enterococcin-1, ampspherin-4, and reyranin-1 exhibited bactericidal activities close to that of polymyxin B [95]. There were 32 optimized AMPs also obtained from low-abundance human oral bacteria by deep learning, of which the most potent AMP pep-19-mod achieved over 95% reduction in bacterial loads in a murine thigh infection model [96]. Due to the limited production of natural AMPs, there is need for deep learning methods and synthetic technologies to modify peptide sequences for more potent AMPs [97,98].

6.5. CRISPR-Cas

CRISPR-Cas, consisting of repeats, spacers, and CRISPR-associated genes, has emerged as a promising tool for combating MDR pathogens (Figure 5). For instance, an I-Fb CRISPR-Cas system in A. baumannii was shown to degrade quorum sensing regulator mRNA, generating reactive oxygen species and reducing biofilm formation and efflux pump activity, which contributed to antibiotic susceptibility such as tetracyclines [99]. CRISPR-based tools are also developed for precise genome editing in A. baumannii, enabling scar-free mutagenesis in MDR strains [100,101]. A CRISPRi system was developed to knock down the essential genes in A. baumannii for bacterial control [102]. An integration of CRISPR-Cas gene editing with toxin-antitoxin module CreTA was designed to combat MDR A. baumannii [103]. However, challenges remain in delivery efficiency, particularly in complex clinical settings, and in avoiding off-target effects [104]. Notably, interdisciplinary collaboration is critical to address ethical concerns and streamline regulatory pathways for clinical adoption [105,106]. With continued innovation, CRISPR-based approaches may revolutionize the treatment of Acinetobacter infections, offering a scalable alternative to traditional antibiotics in the fight against tigecycline-resistant pathogens [107].

7. Conclusions

In summary, the tet(X) genes, especially tet(X3), have spread across multiple Acinetobacter species around the world, threatening the clinical application of tetracycline antibiotics, public health, and food safety. Besides plasmids, ISCR2 is a key element involved in the horizontal transmission of tet(X) genes. There is an urgent need for rapid detection technologies to monitor the tet(X)-positive Acinetobacter sp. strains in different ecological niches, including human, animal, food, and environmental samples. By deep learning tools and screening small-molecule libraries, some novel antibiotics are developed to treat MDR Acinetobacter infections. Under the global policy background of reducing and limiting antibiotics, alternative non-antibiotic approaches such as plant extracts, phages, AMPs, and CRISPR-Cas technologies are promising in eliminating the threat of tet(X)-mediated tigecycline-resistant in Acinetobacter sp. pathogens.

Author Contributions

Conceptualization, C.C.; data curation, T.W., J.L. and J.G.; writing—original draft preparation, C.C. and T.W.; writing—review and editing, C.C.; visualization, T.W. and J.L.; funding acquisition, C.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by National Natural Science Foundation of China (grant number 32402890) and China Postdoctoral Science Foundation (grant number 2023M732993).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
MDRMultidrug-resistant
AMPsAntimicrobial peptides
CRAbCarbapenem-resistant A. baumannii
USFDAUnited States Food and Drug Administration
MICMinimum inhibitory concentration
FADFlavin adenine dinucleotide
NADPHReduced nicotinamide adenine dinucleotide phosphate
WGSWhole genome sequencing
ISInsertion sequence
OTGOrange to green
MALDI-TOF MSMatrix-assisted laser desorption ionization–time of flight mass spectrometry
MCPMacrocyclic peptide
TP2Tilapia piscidin 2

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Figure 1. Mechanism of Tet(X) degrading tetracyclines. (A) Hydroxylation of tetracyclines by Tet(X). (B) Mass spectrometry of tigecycline and its degradation product 11a-hydroxy-tigecycline.
Figure 1. Mechanism of Tet(X) degrading tetracyclines. (A) Hydroxylation of tetracyclines by Tet(X). (B) Mass spectrometry of tigecycline and its degradation product 11a-hydroxy-tigecycline.
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Figure 2. Maximum-likelihood tree of the tet(X) variants in Acinetobacter spp. GenBank accession number, nucleotide sequence length, and tigecycline susceptibility are also provided.
Figure 2. Maximum-likelihood tree of the tet(X) variants in Acinetobacter spp. GenBank accession number, nucleotide sequence length, and tigecycline susceptibility are also provided.
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Figure 3. Spread of tet(X)-positive Acinetobacter spp. in China. The map is mainly generated based on our previous study [30].
Figure 3. Spread of tet(X)-positive Acinetobacter spp. in China. The map is mainly generated based on our previous study [30].
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Figure 4. Distribution of tet(X) variants in different Acinetobacter species in China. The data are mainly collected from our previous study [30].
Figure 4. Distribution of tet(X) variants in different Acinetobacter species in China. The data are mainly collected from our previous study [30].
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Figure 5. Promising treatment options against tet(X)-positive Acinetobacter sp. strains.
Figure 5. Promising treatment options against tet(X)-positive Acinetobacter sp. strains.
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Chen, C.; Wu, T.; Liu, J.; Gao, J. Threat and Control of tet(X)-Mediated Tigecycline-Resistant Acinetobacter sp. Bacteria. Foods 2025, 14, 3374. https://doi.org/10.3390/foods14193374

AMA Style

Chen C, Wu T, Liu J, Gao J. Threat and Control of tet(X)-Mediated Tigecycline-Resistant Acinetobacter sp. Bacteria. Foods. 2025; 14(19):3374. https://doi.org/10.3390/foods14193374

Chicago/Turabian Style

Chen, Chong, Taotao Wu, Jing Liu, and Jie Gao. 2025. "Threat and Control of tet(X)-Mediated Tigecycline-Resistant Acinetobacter sp. Bacteria" Foods 14, no. 19: 3374. https://doi.org/10.3390/foods14193374

APA Style

Chen, C., Wu, T., Liu, J., & Gao, J. (2025). Threat and Control of tet(X)-Mediated Tigecycline-Resistant Acinetobacter sp. Bacteria. Foods, 14(19), 3374. https://doi.org/10.3390/foods14193374

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