Roxanne Nottingham Joseph D. Busch Jason W. Sahl Megan M. Shuey Jeffrey T. Foster James M. Schupp Susan Smith Tonie E. Rocke Paul Klein David M. Wagner Amy J. Vogler 2016 <p><span>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 </span><i>Yersinia pestis</i><span> 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 </span><i>in vitro</i><span> during laboratory cultivation rather than </span><i>in vivo</i><span> during the rodent challenge. In contrast, no single nucleotide polymorphism (SNP) mutations were observed, either </span><i>in vivo</i><span> or </span><i>in vitro</i><span>. These results were consistent with previously published mutation rates and the calculated number of </span><i>Y. pestis</i><span> generations that occurred during the </span><i>in vitro versus</i><span> the </span><i>in vivo</i><span> portions of the experiment. When genotyping disease outbreaks, the potential for </span><i>in vitro</i><span> mutations should be considered, particularly when highly variable genetic markers such as VNTRs are used.</span></p> application/pdf 10.1016/j.meegid.2016.09.019 en Elsevier VNTR diversity in <i>Yersinia pestis</i> isolates from an animal challenge study reveals the potential for <i>in vitro</i> mutations during laboratory cultivation article