Advances in mechanism study on novel tetracycline-inactivating enzymes tet(X) causing emerging tigecycline resistance

Abstract

Abstract:

Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next-generation tetracycline that is the final line of defense against severe infections by carbapenem-resistant Gram-negative bacteria. Unfortunately, this last-resort antibiotic has been challenged by the recent emergence of the mobile tet(X) orthologs that can confer high-level tigecycline resistance. This review will systematically introduce the latest progress in the type, distribution and dissemination, and genetic environment of this orthologs. At present, orthologs of tet(X) mainly includetet(X1), tet(X2), tet(X3), tet(X3.2), tet(X4), tet(X5), tet(X6) and tet(X7). The resistance gene has already been reported in a variety of bacterial hosts and spread to hospital-associated patients and environment in multiple countries/regions. The bacteria carryingtet(X3) andtet(X4) shows the highest resistance level. The insertion sequence ISCR2 is closely related to the horizontal spread oftet(X3),tet(X4) andtet(X5). In particular, the genetic environment oftet(X4) on plasmids is complex, that can be located on various mobile elements, which accelerates the spread of the drug resistance gene. The plasmid-mediated tigecycline resistance may further spread into a variety of ecological niches and into clinical high-risk pathogens and collective efforts are in urgent need to further strengthen the surveillance and research on tigecycline resistance.

Key words:Tigecycline,Resistance mechanisms,Tet(X),Horizontal spread

CLC Number:

R735

SHEN Pinghua, CHEN Huifen. Advances in mechanism study on novel tetracycline-inactivating enzymes tet(X) causing emerging tigecycline resistance[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(01): 75-79.

Figures/Tables1

References35

[1]	YONG D, TOLEMAN M A, GISKE C G, et al. Characte-rization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India[J]. Antimicrob Agents Chemother, 2009, 53(12):5046-5054. doi:10.1128/AAC.00774-09 URL
[2]	LIU Y Y, WANG Y, WALSH T R, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study[J]. Lancet Infect Dis, 2016, 16(2):161-168. doi:10.1016/S1473-3099(15)00424-7 URL
[3]	DOI Y. Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections[J]. Clin Infect Dis, 2019, 69(Suppl 7):S565-S575. doi:10.1093/cid/ciz830 URL
[4]	BEABOUT K, HAMMERSTROM T G, PEREZ A M, et al. The ribosomal S10 protein is a general target for decreased tigecycline susceptibility[J]. Antimicrob Agents Chemother, 2015, 59(9):5561-5566. doi:10.1128/AAC.00547-15pmid:26124155
[5]	SPEER B S, SALYERS A A. Characterization of a novel tetracycline resistance that functions only in aerobically grown Escherichia coli[J]. Antimicrob Agents Chemother, 2015, 59(9):5561-5566. doi:10.1128/AAC.00547-15 URL
[6]	HE T, WANG R, LIU D, et al. Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans[J]. Nat Microbiol, 2019, 4(9):1450-1456. doi:10.1038/s41564-019-0445-2pmid:31133751
[7]	SUN J, CHEN C, CUI C Y, et al. Plasmid-encoded tet(X) genes that confer high-level tigecycline resistance in Escherichia coli[J]. Nat Microbiol, 2019, 4(9):1457-1464. doi:10.1038/s41564-019-0496-4pmid:31235960
[8]	SPEER B S, SALYERS A A. Novel aerobic tetracycline resistance gene that chemically modifies tetracycline[J]. J Bacteriol, 1989, 171(1):148-153. pmid:2644186
[9]	MOORE I F, HUGHES D W, WRIGHT G D. Tigecycline is modified by the flavin-dependent monooxygenase TetX[J]. Biochemistry, 2005, 44(35):11829-11835. pmid:16128584
[10]	WHITTLE G, HUND B D, SHOEMAKER N B, et al. Characterization of the 13-kilobase ermF region of the Bacteroides conjugative transposon CTnDOT[J]. Appl Environ Microbiol, 2001, 67(8):3488-3495. doi:10.1128/AEM.67.8.3488-3495.2001 URL
[11]	YANG W, MOORE I F, KOTEVA K P, et al. TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline antibiotics[J]. J Biol Chem, 2004, 279(50):52346-52352. doi:10.1074/jbc.M409573200pmid:15452119
[12]	WANG L, LIU D, LV Y, et al. Novel Plasmid-Mediated tet(X5) Gene Conferring Resistance to Tigecycline, Eravacycline, and Omadacycline in a Clinical Acinetobacter baumannii Isolate[J]. Antimicrob Agents Chemother, 2019, 64(1):e0132619. doi:10.1128/AAC.01326-19 URL
[13]	LI R, LIU Z, PENG K, et al. Co-occurrence of two tet(X) variants in an Empedobacter brevis of shrimp origin[J]. Antimicrob Agents Chemother, 2019, 63(12):e01636-19.
[14]	LIU D, ZHAI W, SONG H, et al. Identification of the novel tigecycline resistance gene tet(X6) and its variants in Myroides, Acinetobacter and Proteus of food animal origin[J]. J Antimicrob Chemother, 2020, 75(6):1428-1431. doi:10.1093/jac/dkaa037pmid:32068864
[15]	GASPARRINI A J, MARKLEY J L, KUMAR H, et al. Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance[J]. Commun Biol, 2020, 3(1):241. doi:10.1038/s42003-020-0966-5pmid:32415166
[16]	CUI C Y, H E Q, JIA Q L, et al. Evolutionary trajectory of the tet(X) family: critical residue changes towards high-level tigecycline resistance[J]. mSystems, 2021, 6(3):e00050-21.
[17]	GHOSH S, LAPARA T M. The effects of subtherapeutic antibiotic use in farm animals on the proliferation and persistence of antibiotic resistance among soil bacteria[J]. ISME J, 2007, 1(3):191-203. doi:10.1038/ismej.2007.31pmid:18043630
[18]	MING D S, CHEN Q Q, CHEN X T. Analysis of resistance genes in pan-resistant Myroides odoratimimus clinical strain PR63039 using whole genome sequencing[J]. Microb Pathog, 2017, 112:164-170. doi:10.1016/j.micpath.2017.09.012 URL
[19]	LESKI T A, BANGURA U, JIMMY D H, et al. Multidrug-resistant tet(X)-containing hospital isolates in Sierra Leone[J]. Int J Antimicrob Agents, 2013, 42(1):83-86. doi:10.1016/j.ijantimicag.2013.04.014 URL
[20]	SÁRVÁRI K P, SÓKI J, KRISTÓF K, et al. Molecular characterisation of multidrug-resistant Bacteroides isolates from Hungarian clinical samples[J]. J Glob Antimicrob Resist, 2018, 13:65-69. doi:S2213-7165(17)30207-2pmid:29101081
[21]	ZENG J, PAN Y, YANG J, et al. Metagenomic insights into the distribution of antibiotic resistome between the gut-associated environments and the pristine environments[J]. Environ Int, 2019, 126:346-354. doi:S0160-4120(18)33166-0pmid:30826613
[22]	AYDIN S, INCE B, INCE O. Development of antibiotic resistance genes in microbial communities during long-term operation of anaerobic reactors in the treatment of pharmaceutical wastewater[J]. Water Res, 2015, 83:337-344. doi:10.1016/j.watres.2015.07.007pmid:26188597
[23]	USUI M, FUKUDA A, SUZUKI Y, et al. Broad-host-range IncW plasmid harbouring tet(X) in Escherichia coli isolated from pigs in Japan[J]. J Glob Antimicrob Resist, 2022, 28:97-101. doi:10.1016/j.jgar.2021.12.012 URL
[24]	SOLIMAN A M, RAMADAN H, ZARAD H, et al. Coproduction of Tet(X7) conferring high-level tigecycline resistance, fosfomycin FosA4, and colistin mcr-1.1 in escherichia coli strains from chickens in Egypt[J]. Antimicrob Agents Chemother, 2021, 65(6):e02084-20.
[25]	PARK B H, LEVY S B. The cryptic tetracycline resistance determinant on Tn4400 mediates tetracycline degradation as well as tetracycline efflux[J]. Antimicrob Agents Chemother, 1988, 32(12):1797-1800. doi:10.1128/AAC.32.12.1797pmid:3072922
[26]	SONG H, LIU D, LI R, et al. Polymorphism existence of mobile tigecycline resistance gene tet(X4) in escherichia coli[J]. Antimicrob Agents Chemother, 2020, 64(2):e01825-19.
[27]	CHEN C, CUI C Y, ZHANG Y, et al. Emergence of mobile tigecycline resistance mechanism in Escherichia coli strains from migratory birds in China[J]. Emerg Microbes Infect, 2019, 8(1):1219-1222. doi:10.1080/22221751.2019.1653795 URL
[28]	FANG L X, CHEN C, YU D L, et al. Complete nucleotide sequence of a novel plasmid bearing the high-level tigecycline resistance gene tet(X4)[J]. Antimicrob Agents Chemother, 2019, 63(11):e01373-19.
[29]	HE T, WEI R, LI R, et al. Co-existence of tet(X4) and mcr-1 in two porcine escherichia coli isolates[J]. J Antimicrob Chemother, 2020, 75(3):764-766. doi:10.1093/jac/dkz510pmid:31840165
[30]	HE Y Z, LI X P, MIAO Y Y, et al. The IS Apl1 2 dimer circular intermediate participates in mcr-1 transposition[J]. Front Microbiol, 2019, 10:15. doi:10.3389/fmicb.2019.00015 URL
[31]	TOLEMAN M A, BENNETT P M, WALSH T R. ISCR elements: novel gene-capturing systems of the 21st century?[J]. Microbiol Mol Biol Rev, 2006, 70(2):296-316. doi:10.1128/MMBR.00048-05 URL
[32]	LI R, PENG K, LI Y, et al. Exploring tet(X)-bearing tigecycline-resistant bacteria of swine farming environments[J]. Sci Total Environ, 2020, 733:139306. doi:10.1016/j.scitotenv.2020.139306 URL
[33]	CHENG Y, CHEN Y, LIU Y, et al. Detection of a new tet(X6)-encoding plasmid in Acinetobacter towneri[J]. J Glob Antimicrob Resist, 2021, 25:132-136. doi:10.1016/j.jgar.2021.03.004pmid:33762210
[34]	HSIEH Y C, WU J W, CHEN Y Y, et al. An outbreak of tet(X6)-carrying tigecycline-resistant acinetobacter baumannii isolates with a new capsular type at a hospital in taiwan[J]. Antibiotics (Basel), 2021, 10(10):1239.
[35]	ROBERTS M C. Environmental macrolide-lincosamide-streptogramin and tetracycline resistant bacteria[J]. Front Microbiol, 2011, 2:40. doi:10.3389/fmicb.2011.00040pmid:21833302