TY - JOUR
T1 - Investigation of Yersinia pestis laboratory adaptation through a combined genomics and proteomics approach
AU - Leiser, Owen P.
AU - Merkley, Eric D.
AU - Clowers, Brian H.
AU - Deatherage Kaiser, Brooke L.
AU - Lin, Andy
AU - Hutchison, Janine R.
AU - Melville, Angela M.
AU - Wagner, David M.
AU - Keim, Paul S.
AU - Foster, Jeffrey T.
AU - Kreuzer, Helen W.
N1 - Funding Information:
This work was supported by Defense Threat Reduction Agency Basic Research Award DTRA10027IA-2129 and by the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory, a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy. Battelle Memorial Institute operates Pacific Northwest National Laboratory for the U.S. DOE under Contract DE-AC06-76RLO. The funders authorized publication, but had no role in study design, data collection and analysis, or preparation of the manuscript. We thank Adina Doyle and Nicolette Janke for preparing DNA libraries for sequencing, and Janine Hutchison for valuable assistance in preparing samples for proteomic analyses. This work was supported by Defense Threat Reduction Agency Basic Research Award DTRA10027IA-2129 and by the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory, a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy. Battelle Memorial Institute operates Pacific Northwest National Laboratory for the U.S. DOE under Contract DE-AC06-76RLO. The funders authorized publication, but had no role in study design, data collection and analysis, or preparation of the manuscript.
Publisher Copyright:
© 2015 Leiser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - The bacterial pathogen Yersinia pestis, the cause of plague in humans and animals, normally has a sylvatic lifestyle, cycling between fleas and mammals. In contrast, laboratorygrown Y. pestis experiences a more constant environment and conditions that it would not normally encounter. The transition from the natural environment to the laboratory results in a vastly different set of selective pressures, and represents what could be considered domestication. Understanding the kinds of adaptations Y. pestis undergoes as it becomes domesticated will contribute to understanding the basic biology of this important pathogen. In this study, we performed a parallel serial passage experiment (PSPE) to explore the mechanisms by which Y. pestis adapts to laboratory conditions, hypothesizing that cells would undergo significant changes in virulence and nutrient acquisition systems. Two wild strains were serially passaged in 12 independent populations each for ∼750 generations, after which each population was analyzed using whole-genome sequencing, LC-MS/MS proteomic analysis, and GC/MS metabolomics. We observed considerable parallel evolution in the endpoint populations, detecting multiple independent mutations in ail, pepA, and zwf, suggesting that specific selective pressures are shaping evolutionary responses. Complementary LC-MS/MS proteomic data provide physiological context to the observed mutations, and reveal regulatory changes not necessarily associated with specific mutations, including changes in amino acid metabolism and cell envelope biogenesis. Proteomic data support hypotheses generated by genomic data in addition to suggesting future mechanistic studies, indicating that future whole-genome sequencing studies be designed to leverage proteomics as a critical complement.
AB - The bacterial pathogen Yersinia pestis, the cause of plague in humans and animals, normally has a sylvatic lifestyle, cycling between fleas and mammals. In contrast, laboratorygrown Y. pestis experiences a more constant environment and conditions that it would not normally encounter. The transition from the natural environment to the laboratory results in a vastly different set of selective pressures, and represents what could be considered domestication. Understanding the kinds of adaptations Y. pestis undergoes as it becomes domesticated will contribute to understanding the basic biology of this important pathogen. In this study, we performed a parallel serial passage experiment (PSPE) to explore the mechanisms by which Y. pestis adapts to laboratory conditions, hypothesizing that cells would undergo significant changes in virulence and nutrient acquisition systems. Two wild strains were serially passaged in 12 independent populations each for ∼750 generations, after which each population was analyzed using whole-genome sequencing, LC-MS/MS proteomic analysis, and GC/MS metabolomics. We observed considerable parallel evolution in the endpoint populations, detecting multiple independent mutations in ail, pepA, and zwf, suggesting that specific selective pressures are shaping evolutionary responses. Complementary LC-MS/MS proteomic data provide physiological context to the observed mutations, and reveal regulatory changes not necessarily associated with specific mutations, including changes in amino acid metabolism and cell envelope biogenesis. Proteomic data support hypotheses generated by genomic data in addition to suggesting future mechanistic studies, indicating that future whole-genome sequencing studies be designed to leverage proteomics as a critical complement.
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U2 - 10.1371/journal.pone.0142997
DO - 10.1371/journal.pone.0142997
M3 - Article
C2 - 26599979
AN - SCOPUS:84957591292
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 11
M1 - e0142997
ER -