Whole-Genome Sequencing for Detecting Antimicrobial Resistance in Nontyphoidal Salmonella.

Patrick F McDermott, Gregory H Tyson, Claudine Kabera, Yuansha Chen, Cong Li, Jason P Folster, Sherry L Ayers, Claudia Lam, Heather P Tate, Shaohua Zhao
Author Information
  1. Patrick F McDermott: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA Patrick.McDermott@fda.hhs.gov.
  2. Gregory H Tyson: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  3. Claudine Kabera: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  4. Yuansha Chen: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  5. Cong Li: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  6. Jason P Folster: Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  7. Sherry L Ayers: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  8. Claudia Lam: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  9. Heather P Tate: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.
  10. Shaohua Zhao: Division of Animal and Food Microbiology, Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, Maryland, USA.

Abstract

Laboratory-based in vitro antimicrobial susceptibility testing is the foundation for guiding anti-infective therapy and monitoring antimicrobial resistance trends. We used whole-genome sequencing (WGS) technology to identify known antimicrobial resistance determinants among strains of nontyphoidal Salmonella and correlated these with susceptibility phenotypes to evaluate the utility of WGS for antimicrobial resistance surveillance. Six hundred forty Salmonella of 43 different serotypes were selected from among retail meat and human clinical isolates that were tested for susceptibility to 14 antimicrobials using broth microdilution. The MIC for each drug was used to categorize isolates as susceptible or resistant based on Clinical and Laboratory Standards Institute clinical breakpoints or National Antimicrobial Resistance Monitoring System (NARMS) consensus interpretive criteria. Each isolate was subjected to whole-genome shotgun sequencing, and resistance genes were identified from assembled sequences. A total of 65 unique resistance genes, plus mutations in two structural resistance loci, were identified. There were more unique resistance genes (n = 59) in the 104 human isolates than in the 536 retail meat isolates (n = 36). Overall, resistance genotypes and phenotypes correlated in 99.0% of cases. Correlations approached 100% for most classes of antibiotics but were lower for aminoglycosides and beta-lactams. We report the first finding of extended-spectrum β-lactamases (ESBLs) (blaCTX-M1 and blaSHV2a) in retail meat isolates of Salmonella in the United States. Whole-genome sequencing is an effective tool for predicting antibiotic resistance in nontyphoidal Salmonella, although the use of more appropriate surveillance breakpoints and increased knowledge of new resistance alleles will further improve correlations.

References

  1. J Antimicrob Chemother. 2003 Apr;51(4):1001-5 [PMID: 12654733]
  2. Hum Genomics. 2015 Aug 05;9:19 [PMID: 26243131]
  3. J Clin Microbiol. 2015 May;53(5):1685-92 [PMID: 25762776]
  4. Appl Environ Microbiol. 2015 Oct 30;82(2):459-66 [PMID: 26519386]
  5. Comp Immunol Microbiol Infect Dis. 2013 Jan;36(1):9-16 [PMID: 22963790]
  6. Ups J Med Sci. 2014 May;119(2):78-86 [PMID: 24836050]
  7. J Clin Microbiol. 2014 Apr;52(4):1182-91 [PMID: 24501024]
  8. Genome Biol Evol. 2014 May;6(5):1046-68 [PMID: 24732280]
  9. Emerg Infect Dis. 2014 Aug;20(8):1306-14 [PMID: 25062035]
  10. Mol Biol Evol. 2013 Dec;30(12):2725-9 [PMID: 24132122]
  11. J Antimicrob Chemother. 1998 Jun;41(6):635-41 [PMID: 9687102]
  12. BMC Genomics. 2012 Jan 19;13:32 [PMID: 22260654]
  13. Antimicrob Agents Chemother. 1991 Aug;35(8):1647-50 [PMID: 1656869]
  14. J Antimicrob Chemother. 2013 Oct;68(10 ):2234-44 [PMID: 23722448]
  15. Emerg Infect Dis. 2008 Dec;14(12):1957-9 [PMID: 19046536]
  16. Microb Drug Resist. 2010 Dec;16(4):245-8 [PMID: 20624094]
  17. Future Microbiol. 2007 Oct;2(5):493-500 [PMID: 17927472]
  18. J Infect Dis. 2016 Feb 15;213(4):502-8 [PMID: 25995194]
  19. Antimicrob Agents Chemother. 2013 Jan;57(1):658-60 [PMID: 23147728]
  20. FEMS Microbiol Lett. 2016 Feb;363(4):null [PMID: 26781915]
  21. Clin Infect Dis. 2009 Dec 1;49(11):1749-55 [PMID: 19857164]
  22. Nat Rev Genet. 2012 Sep;13(9):601-12 [PMID: 22868263]
  23. Emerg Infect Dis. 2008 Feb;14 (2):340-2 [PMID: 18258138]
  24. J Clin Microbiol. 2006 Oct;44(10):3569-77 [PMID: 17021084]
  25. J Antimicrob Chemother. 2013 Apr;68(4):771-7 [PMID: 23233485]
  26. OMICS. 2008 Jun;12(2):137-41 [PMID: 18416670]
  27. J Clin Microbiol. 2007 Aug;45(8):2740-2 [PMID: 17567787]
  28. Microb Drug Resist. 2012 Feb;18(1):88-93 [PMID: 21749212]
  29. Biol Chem. 2014 May;395(5):559-75 [PMID: 24497223]
  30. J Antimicrob Chemother. 2015 Oct;70(10):2763-9 [PMID: 26142410]
  31. Emerg Infect Dis. 2015 Sep;21(9):1582-8 [PMID: 26291736]

MeSH Term

Anti-Bacterial Agents
Drug Resistance, Multiple, Bacterial
Genotype
Humans
Meat
Microbial Sensitivity Tests
Mutation
Phenotype
Salmonella
United States
beta-Lactamases
beta-Lactams

Chemicals

Anti-Bacterial Agents
beta-Lactams
beta-Lactamases

Word Cloud

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