Exploring the third-generation tetracycline resistance of multidrug-resistant livestock-associated methicillin-resistant Staphylococcus aureus ST9 across healthcare settings in China.

Yiyi Chen, Lu Sun, Yueqin Hong, Mengzhen Chen, Hao Zhang, Yaqin Peng, Kang Liao, Haiping Wang, Feiteng Zhu, Hemu Zhuang, Zhengan Wang, Shengnan Jiang, Yunsong Yu, Yan Chen
Author Information
  1. Yiyi Chen: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  2. Lu Sun: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  3. Yueqin Hong: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  4. Mengzhen Chen: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  5. Hao Zhang: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  6. Yaqin Peng: Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  7. Kang Liao: Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  8. Haiping Wang: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  9. Feiteng Zhu: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  10. Hemu Zhuang: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  11. Zhengan Wang: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  12. Shengnan Jiang: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  13. Yunsong Yu: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. ORCID
  14. Yan Chen: Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. ORCID

Abstract

BACKGROUND: The overuse of antibiotics in livestock is contributing to the burden of antimicrobial resistance in humans, representing a One Health challenge. Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has recently become a growing concern, and ST9 is the major LA-MRSA lineage in China and has emerged in clinical settings.
METHODS: Antimicrobial susceptibility testing was used to evaluate the tetracycline resistance of ST9 MRSA collections, and gene cloning experiments were performed to explore the resistance mechanisms. Whole-genome sequencing and comparative genomics were used to analyse the genetic features of clinical ST9 isolates. A phylogenetic tree was constructed to investigate the relationship of human- and livestock-derived ST9 isolates.
RESULTS: Clinical ST9 isolates were found to possess several types of resistance genes and resistance-related mutations and were multidrug-resistant. Notably, all clinical ST9 isolates were resistant to third-generation tetracyclines. Cloning experiments showed that both the acquisition of the tetracycline resistance gene tet(L)/tet(63) and a mutation in the rpsJ gene contributed to third-generation tetracycline resistance. Phylogenetic analysis showed that the ST9 isolates collected in healthcare systems were probably transmitted from livestock. The ST9 lineage underwent multiple interspecies recombination events and gained many resistance elements. Furthermore, the resistance to third-generation tetracyclines may have evolved under tetracycline pressure in livestock.
CONCLUSIONS: The evolution of ST9 MRSA in livestock and transmission of this clone between humans and livestock highlight the importance of establishing control strategies with the One Health approach to reduce the burden of antibiotic resistance.

References

  1. Zoonoses Public Health. 2013 Dec;60(8):572-6 [PMID: 23279691]
  2. Infect Genet Evol. 2018 Dec;66:188-191 [PMID: 30268919]
  3. J Antimicrob Chemother. 2015 Aug;70(8):2182-90 [PMID: 25977397]
  4. Int J Antimicrob Agents. 2019 Jul;54(1):8-15 [PMID: 30959181]
  5. J Antimicrob Chemother. 2020 Feb 1;75(2):484-486 [PMID: 31670809]
  6. Mol Biol Evol. 2020 May 1;37(5):1530-1534 [PMID: 32011700]
  7. Adv Sci (Weinh). 2022 Feb;9(4):e2103388 [PMID: 34894204]
  8. Emerg Infect Dis. 2005 May;11(5):711-4 [PMID: 15890125]
  9. Antimicrob Resist Infect Control. 2020 Apr 22;9(1):56 [PMID: 32321574]
  10. Int J Antimicrob Agents. 2015 Nov;46(5):572-5 [PMID: 26364847]
  11. Drugs. 2020 Feb;80(3):285-313 [PMID: 31970713]
  12. J Antimicrob Chemother. 2021 Feb 11;76(3):576-581 [PMID: 33247717]
  13. Clin Infect Dis. 2017 Oct 1;65(7):1072-1076 [PMID: 28575216]
  14. J Glob Antimicrob Resist. 2013 Jun;1(2):55-62 [PMID: 27873579]
  15. Clin Microbiol Infect. 2012 Aug;18(8):745-55 [PMID: 22509728]
  16. Emerg Microbes Infect. 2020 Dec;9(1):2526-2535 [PMID: 33174510]
  17. BMC Infect Dis. 2013 May 11;13:214 [PMID: 23663295]
  18. Antimicrob Agents Chemother. 2000 Sep;44(9):2530-3 [PMID: 10952608]
  19. Clin Microbiol Rev. 2021 Feb 10;34(2): [PMID: 33568553]
  20. Antimicrob Agents Chemother. 2017 Feb 23;61(3): [PMID: 27993854]
  21. Biol Chem. 2014 May;395(5):559-75 [PMID: 24497223]
  22. Int J Antimicrob Agents. 2015 Apr;45(4):334-40 [PMID: 25593014]
  23. Clin Microbiol Infect. 2022 Jan;28(1):85-92 [PMID: 34022399]
  24. Nat Microbiol. 2019 Sep;4(9):1432-1442 [PMID: 31439928]
  25. J Infect Dis. 2020 Mar 16;221(Suppl 2):S220-S228 [PMID: 32176793]
  26. Pharmaceutics. 2021 Dec 05;13(12): [PMID: 34959366]
  27. Antimicrob Resist Infect Control. 2018 May 30;7:68 [PMID: 29876099]
  28. J Antimicrob Chemother. 2018 Oct 1;73(10):2652-2661 [PMID: 29986036]
  29. Panminerva Med. 2020 Jun;62(2):116-117 [PMID: 30311759]
  30. Int J Antimicrob Agents. 2017 Dec;50(6):739-741 [PMID: 29038088]
  31. Euro Surveill. 2010 Apr 22;15(16): [PMID: 20430001]
  32. Antimicrob Agents Chemother. 2020 Feb 21;64(3): [PMID: 31843997]
  33. mSystems. 2021 Jun 29;6(3):e0049221 [PMID: 34156294]
  34. Nat Microbiol. 2019 Sep;4(9):1450-1456 [PMID: 31133751]
  35. Vet Microbiol. 2017 Feb;200:6-12 [PMID: 26658156]
  36. Clin Microbiol Rev. 2018 Sep 12;31(4): [PMID: 30209034]
  37. Genome Biol. 2020 Jul 22;21(1):180 [PMID: 32698896]
  38. mBio. 2012 Feb 28;3(2): [PMID: 22375071]
  39. Emerg Infect Dis. 2005 Dec;11(12):1965-6 [PMID: 16485492]
  40. Appl Environ Microbiol. 2015 May 1;81(9):3243-54 [PMID: 25747000]
  41. Vet Microbiol. 2022 Feb;265:109329 [PMID: 35030381]
  42. Antimicrob Agents Chemother. 2020 Apr 21;64(5): [PMID: 32071045]
  43. J Antimicrob Chemother. 2021 Jun 18;76(7):1703-1711 [PMID: 33822977]
  44. Lancet Infect Dis. 2016 Feb;16(2):161-8 [PMID: 26603172]

MeSH Term

Animals
Humans
Methicillin-Resistant Staphylococcus aureus
Livestock
Tetracycline Resistance
Phylogeny
Staphylococcal Infections
Anti-Bacterial Agents
Tetracycline
China

Chemicals

Anti-Bacterial Agents
Tetracycline

Word Cloud

Created with Highcharts 10.0.0resistanceST9livestocktetracyclineisolatesthird-generationclinicalgeneburdenhumansOneHealthmethicillin-resistantStaphylococcusaureusLA-MRSAlineageChinasettingsusedMRSAexperimentsmultidrug-resistanttetracyclinesshowedhealthcareBACKGROUND:overuseantibioticscontributingantimicrobialrepresentingchallengeLivestock-associatedrecentlybecomegrowingconcernmajoremergedMETHODS:AntimicrobialsusceptibilitytestingevaluatecollectionscloningperformedexploremechanismsWhole-genomesequencingcomparativegenomicsanalysegeneticfeaturesphylogenetictreeconstructedinvestigaterelationshiphuman-livestock-derivedRESULTS:Clinicalfoundpossessseveraltypesgenesresistance-relatedmutationsNotablyresistantCloningacquisitiontetL/tet63mutationrpsJcontributedPhylogeneticanalysiscollectedsystemsprobablytransmittedunderwentmultipleinterspeciesrecombinationeventsgainedmanyelementsFurthermoremayevolvedpressureCONCLUSIONS:evolutiontransmissionclonehighlightimportanceestablishingcontrolstrategiesapproachreduceantibioticExploringlivestock-associatedacross

Similar Articles

Cited By