VNTR diversity in Yersinia pestis isolates from an animal challenge study reveals the potential for in vitro mutations during laboratory cultivation

Amy J. Vogler, Roxanne Nottingham, Joseph D. Busch, Jason W. Sahl, Megan M. Shuey, Jeffrey T Foster, James M. Schupp, Susan R. Smith, Tonie E. Rocke, Paul S Keim, David M Wagner

Research output: Contribution to journalArticle


Underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. Although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. Here, we investigated tissue samples and Yersinia pestis isolates from a rodent laboratory challenge with strain CO92 using whole genome sequencing and multi-locus variable-number tandem repeat (VNTR) analysis (MLVA). We identified six VNTR mutations that were found to have occurred in vitro during laboratory cultivation rather than in vivo during the rodent challenge. In contrast, no single nucleotide polymorphism (SNP) mutations were observed, either in vivo or in vitro. These results were consistent with previously published mutation rates and the calculated number of Y. pestis generations that occurred during the in vitro versus the in vivo portions of the experiment. When genotyping disease outbreaks, the potential for in vitro mutations should be considered, particularly when highly variable genetic markers such as VNTRs are used.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalInfection, Genetics and Evolution
StatePublished - Nov 1 2016



  • MLVA
  • Mutation
  • Prairie dog
  • SNP
  • VNTR
  • Yersinia pestis

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

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