{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:39:15Z","timestamp":1791920355165,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding the mechanisms leading to the rise and dissemination of antimicrobial resistance (AMR) is crucially important for the preservation of power of antimicrobials and controlling infectious diseases. Measures to monitor and detect AMR, however, have been significantly delayed and introduced much later after the beginning of industrial production and consumption of antimicrobials. However, monitoring and detection of AMR is largely focused on bacterial pathogens, thus missing multiple key events which take place before the emergence and spread of AMR among the pathogens. In this regard, careful analysis of AMR development towards recently introduced antimicrobials may serve as a valuable example for the better understanding of mechanisms driving AMR evolution. Here, the example of evolution of tet(X), which confers resistance to the next-generation tetracyclines, is summarised and discussed. Initial mechanisms of resistance to these antimicrobials among pathogens were mostly via chromosomal mutations leading to the overexpression of efflux pumps. High-level resistance was achieved only after the acquisition of flavin-dependent monooxygenase-encoding genes from the environmental microbiota. These genes confer resistance to all tetracyclines, including the next-generation tetracyclines, and thus were termed tet(X). ISCR2 and IS26, as well as a variety of conjugative and mobilizable plasmids of different incompatibility groups, played an essential role in the acquisition of tet(X) genes from natural reservoirs and in further dissemination among bacterial commensals and pathogens. This process, which took place within the last decade, demonstrates how rapidly AMR evolution may progress, taking away some drugs of last resort from our arsenal.<\/jats:p>","DOI":"10.3390\/ijms22083905","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"3905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study"],"prefix":"10.3390","volume":"22","author":[{"given":"Rustam","family":"Aminov","sequence":"first","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK"},{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1128\/AAC.43.6.1523","article-title":"Nomenclature for New Tetracycline Resistance Determinants","volume":"43","author":"Levy","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1111\/j.1462-2920.2009.01972.x","article-title":"The role of antibiotics and antibiotic resistance in nature","volume":"11","author":"Aminov","year":"2009","journal-title":"Environ. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52346","DOI":"10.1074\/jbc.M409573200","article-title":"TetX Is a Flavin-dependent Monooxygenase Conferring Resistance to Tetracycline Antibiotics","volume":"279","author":"Yang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11829","DOI":"10.1021\/bi0506066","article-title":"Tigecycline Is Modified by the Flavin-Dependent Monooxygenase TetX","volume":"44","author":"Moore","year":"2005","journal-title":"Biochemistry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fmicb.2013.00192","article-title":"Evolution in action: Dissemination of tet(X) into pathogenic microbiota","volume":"4","author":"Aminov","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijantimicag.2013.04.014","article-title":"Multidrug-resistant tet(X)-containing hospital isolates in Sierra Leone","volume":"42","author":"Leski","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/03079457.2010.507761","article-title":"Prevalence and molecular characterization of chloramphenicol resistance in Riemerella anatipestifer isolated from ducks and geese in Taiwan","volume":"39","author":"Chen","year":"2010","journal-title":"Avian Pathol."},{"key":"ref_8","unstructured":"Calnek, B.W., Barnes, H.J., Beard, H.J., McDougald, L.R., and Saif, Y.M. (1997). Riemerella anatipestifer infection. Diseases of Poultry, Iowa State University Press. [10th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1439-0450.2001.00471.x","article-title":"Studies on the prevalence of Riemerella anatipestifer in the upper respiratory tract of clinically healthy ducklings and characterization of untypable strains","volume":"48","author":"Ryll","year":"2001","journal-title":"J. Vet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1637\/7248-073004R1","article-title":"The Effect of Route of Inoculation and Challenge Dosage on Riemerella anatipestifer Infection in Pekin Ducks (Anas platyrhynchos)","volume":"49","author":"Sarver","year":"2005","journal-title":"Avian Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3389\/fmicb.2018.00585","article-title":"Various Profiles of tet Genes Addition to tet(X) in Riemerella anatipestifer Isolates from Ducks in China","volume":"9","author":"Zhu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_12","unstructured":"Mirete, S., P\u00e9rez, M.L., and de Ardoz, T. (2017). Chapter 8: Agricultural use of antibiotics and antibiotic resistance. Antibiotic Resistance Genes in Natural Environments and Long-Term Effects, Nova Science Publishers, Inc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fmicb.2011.00158","article-title":"Horizontal Gene Exchange in Environmental Microbiota","volume":"2","author":"Aminov","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/003335491212700103","article-title":"A Review of Antibiotic Use in Food Animals: Perspective, Policy, and Potential","volume":"127","author":"Landers","year":"2012","journal-title":"Public Health Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/s41564-019-0445-2","article-title":"Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans","volume":"4","author":"He","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/s41564-019-0496-4","article-title":"Plasmid-encoded tet(X) genes that confer high-level tigecycline resistance in Escherichia coli","volume":"4","author":"Sun","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1080\/22221751.2019.1678367","article-title":"Plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from food-producing animals, China, 2008\u20132018","volume":"8","author":"Sun","year":"2019","journal-title":"Emerg. Microb. Infect."},{"key":"ref_18","first-page":"1","article-title":"Epidemiological and phylogenetic analysis reveals Flavobacteriaceae as potential ancestral source of tigecycline resistance gene tet(X)","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-020-00807-5","article-title":"Genetic diversity and characteristics of high-level tigecycline resistance Tet(X) in Acinetobacter species","volume":"12","author":"Chen","year":"2020","journal-title":"Genome Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/jac\/dkaa012","article-title":"A novel tigecycline resistance gene, tet(X6), on an SXT\/R391 integrative and conjugative element in a Proteus genomospecies 6 isolate of retail meat origin","volume":"75","author":"He","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1093\/jac\/dkaa037","article-title":"Identification of the novel tigecycline resistance gene tet(X6) and its variants in Myroides, Acinetobacter and Proteus of food animal origin","volume":"75","author":"Liu","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108954","DOI":"10.1016\/j.vetmic.2020.108954","article-title":"Spread of tet(X5) and tet(X6) genes in multidrug-resistant Acinetobacter baumannii strains of animal origin","volume":"253","author":"Chen","year":"2021","journal-title":"Vet. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2000014","DOI":"10.1002\/bies.202000014","article-title":"Emerging High-Level Tigecycline Resistance: Novel Tetracycline Destructases Spread via the Mobile Tet(X)","volume":"42","author":"Fang","year":"2020","journal-title":"BioEssays"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, R., Lu, X., Peng, K., Liu, Z., Li, Y., Liu, Y., Xiao, X., and Wang, Z. (2020). Deciphering the Structural Diversity and Classification of the Mobile Tigecycline Resistance Gene tet(X)-Bearing Plasmidome among Bacteria. mSystems, 5.","DOI":"10.1128\/mSystems.00134-20"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s40265-016-0545-8","article-title":"Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent","volume":"76","author":"Zhanel","year":"2016","journal-title":"Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1016\/j.bmc.2016.07.029","article-title":"Discovery, pharmacology, and clinical profile of omadacycline, a novel aminomethylcycline antibiotic","volume":"24","author":"Tanaka","year":"2016","journal-title":"Bioorganic Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.15190\/d.2019.15","article-title":"FDA approved antibacterial drugs: 2018\u20132019","volume":"7","author":"Andrei","year":"2019","journal-title":"Discoveries"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"01326-19","DOI":"10.1128\/AAC.01326-19","article-title":"Novel plasmid-mediated tet(X5) gene conferring resistance to tigecycline, eravacycline and omadacycline in clinical Acinetobacter baumannii","volume":"64","author":"Wang","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1080\/22221751.2020.1803769","article-title":"Identification of novel tetracycline resistance gene tet(X14) and its co-occurrence with tet(X2) in a tigecycline-resistant and colistin-resistant Empedobacter stercoris","volume":"9","author":"Cheng","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s42003-020-0966-5","article-title":"Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance","volume":"3","author":"Gasparrini","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.abb.2013.12.005","article-title":"Flavin dependent monooxygenases","volume":"544","author":"Huijbers","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108765","DOI":"10.1016\/j.abb.2021.108765","article-title":"New frontiers in flavin-dependent monooxygenases","volume":"699","author":"Reis","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1128\/AAC.41.1.218","article-title":"Monooxygenase-like sequence of a Rhodococcus equi gene confer-ring increased resistance to rifampin by inactivating this antibiotic","volume":"41","author":"Andersen","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ja.2009.116","article-title":"Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: Structure elucidation, gene identification and role in drug resistance","volume":"63","author":"Hoshino","year":"2010","journal-title":"J. Antibiot."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1021\/acs.biochem.8b00190","article-title":"Structural evidence for rifampicin monooxygenase inactivating rifampicin by cleaving its ansabridge","volume":"57","author":"Liu","year":"2018","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1128\/AAC.01088-15","article-title":"Escherichia coli overexpressing a baeyer-villiger monooxygenase from Acinetobacter radioresistens becomes resistant to imipenem","volume":"60","author":"Minerdi","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1073\/pnas.72.7.2621","article-title":"Sulfonamide resistance mechanism in Escherichia coli: R plasmids can determine sulfonamide-resistant dihydropteroate synthases","volume":"72","author":"Wise","year":"1975","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-16132-8","article-title":"FMNH2-dependent monooxygenases initiate catabolism of sulfonamides in Microbacterium sp. strain BR1 subsisting on sulfonamide antibiotics","volume":"7","author":"Ricken","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.envint.2019.03.046","article-title":"A novel sulfonamide resistance mechanism by two-component flavin-dependent monooxygenase system in sulfonamide-degrading actinobacteria","volume":"127","author":"Kim","year":"2019","journal-title":"Environ. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1080\/03079459708419253","article-title":"Dose response study of enrofloxacin against Riemerella anatipestifer septicaemia in Muscovy and Pekin ducklings","volume":"26","author":"Turbahn","year":"1997","journal-title":"Avian Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3382\/ps.0591027","article-title":"Effects of chemotherapeutic agents on Pasteurella anatipestifer infection in White Pekin ducklings","volume":"59","author":"Sandhu","year":"1980","journal-title":"Poult. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.3382\/ps.2007-00249","article-title":"History of the Use of Antibiotic as Growth Promoters in European Poultry Feeds","volume":"86","author":"Castanon","year":"2007","journal-title":"Poult. Sci."},{"key":"ref_43","first-page":"1","article-title":"Tetracyclines in Food and Feedingstuffs: From Regulation to Analytical Methods, Bacterial Resistance, and Environmental and Health Implications","volume":"2017","year":"2017","journal-title":"J. Anal. Methods Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1057\/s41599-018-0152-2","article-title":"Pharming animals: A global history of antibiotics in food production (1935\u20132017)","volume":"4","author":"Kirchhelle","year":"2018","journal-title":"Palgrave Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13756-015-0050-y","article-title":"Antimicrobial use in Chinese swine and broiler poultry production","volume":"4","author":"Krishnasamy","year":"2015","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1093\/molbev\/msh049","article-title":"Fast Minimum Evolution","volume":"21","author":"Desper","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1900340","DOI":"10.2807\/1560-7917.ES.2019.24.25.1900340","article-title":"Detection of plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from pork, Sichuan and Shandong Provinces, China, February 2019","volume":"24","author":"Bai","year":"2019","journal-title":"Eurosurveillance"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1128\/AAC.00383-10","article-title":"ISCR Elements Are Key Players in IncA\/C Plasmid Evolution","volume":"54","author":"Toleman","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1128\/MMBR.00048-05","article-title":"ISCR Elements: Novel Gene-Capturing Systems of the 21st Century?","volume":"70","author":"Toleman","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s00203-017-1365-2","article-title":"ISCR2 is associated with the dissemination of multiple resistance genes among Vibrio spp. and Pseudoalteromonas spp. isolated from farmed fish","volume":"199","author":"Xu","year":"2017","journal-title":"Arch. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e00762-15","DOI":"10.1128\/mBio.00762-15","article-title":"Insertion Sequence IS26 Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition","volume":"6","author":"He","year":"2015","journal-title":"mBio"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/j.1462-2920.2008.01819.x","article-title":"Spreading antibiotic resistance through spread manure: Characteristics of a novel plasmid type with low %G+C content","volume":"11","author":"Heuer","year":"2008","journal-title":"Environ. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nrmicro1789","article-title":"An increasing threat in hospitals: Multidrug-resistant Acinetobacter baumannii","volume":"5","author":"Dijkshoorn","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1086\/533452","article-title":"Federal Funding for the Study of Antimicrobial Resistance in Nosocomial Pathogens: No ESKAPE","volume":"197","author":"Rice","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/595011","article-title":"Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America","volume":"48","author":"Boucher","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_56","first-page":"33","article-title":"ISCR2 and IS26: Two insertion sequences highly dispersed among Acinetobacter spp. clinical strains","volume":"4","author":"Almuzara","year":"2017","journal-title":"J Bacteriol Mycol Open Access."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/jac\/dkaa384","article-title":"Characterization of three porcine Escherichia coli isolates co-harbouring tet(X4) and cfr","volume":"76","author":"Tang","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1128\/AEM.67.8.3488-3495.2001","article-title":"Characterization of the 13-kilobase ermF region of the Bacteroides conjugative transposon CTnDOT","volume":"67","author":"Whittle","year":"2001","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1111\/j.1365-2672.2008.04101.x","article-title":"Sphingobacterium sp. strain PM2-P1-29 harbours a functional tet(X) gene encoding for the degradation of tetracycline","volume":"106","author":"Ghosh","year":"2009","journal-title":"J. Appl. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0140-6736(97)07322-4","article-title":"Quinolone resistance from a transferable plasmid","volume":"351","author":"Pascual","year":"1998","journal-title":"Lancet"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1128\/AAC.49.8.3523-3525.2005","article-title":"Origin of Plasmid-Mediated Quinolone Resistance Determinant QnrA","volume":"49","author":"Poirel","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ruiz, J. (2019). Transferable Mechanisms of Quinolone Resistance from 1998 Onward. Clin. Microbiol. Rev., 32.","DOI":"10.1128\/CMR.00007-19"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s42003-020-01545-5","article-title":"A framework for identifying the recent origins of mobile antibiotic resistance genes","volume":"4","author":"Ebmeyer","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1128\/AAC.01198-06","article-title":"Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii","volume":"51","author":"Peleg","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1128\/AAC.00732-07","article-title":"AdeIJK, a Resistance-Nodulation-Cell Division Pump Effluxing Multiple Antibiotics in Acinetobacter baumannii","volume":"52","author":"Magnet","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/mdr.2006.9990","article-title":"RamA, a Transcriptional Regulator, and AcrAB, an RND-Type Efflux Pump, are Associated with Decreased Susceptibility to Tigecycline in Enterobacter cloacae","volume":"13","author":"Keeney","year":"2007","journal-title":"Microb. Drug Resist."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/jac\/dkm397","article-title":"MarA-mediated overexpression of the AcrAB efflux pump results in decreased susceptibility to tigecycline in Escherichia coli","volume":"61","author":"Keeney","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"96615","DOI":"10.18632\/oncotarget.19633","article-title":"Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_69","first-page":"e000455","article-title":"Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes","volume":"6","author":"Berglund","year":"2020","journal-title":"Microb. Genom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:40Z","timestamp":1760362000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/3905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,9]]},"references-count":69,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22083905"],"URL":"https:\/\/doi.org\/10.3390\/ijms22083905","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,9]]}}}