title: Investigation of Yersinia pestis Laboratory Adaptation through a Combined Genomics and Proteomics Approach.
abstract: 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, laboratory-grown 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.
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, 86001, United States of America.
authors.forename: Owen P
authors.initials: OP
authors.lastname: Leiser
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, 99352, United States of America.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Merkley
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA, 99354, United States of America.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Clowers
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, 99352, United States of America.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Deatherage Kaiser
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, 99352, United States of America.
authors.forename: Andy
authors.initials: A
authors.lastname: Lin
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, 99352, United States of America.
authors.forename: Janine R
authors.initials: JR
authors.lastname: Hutchison
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, 99352, United States of America.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Melville
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, 86001, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Wagner
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, 86001, United States of America.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Keim
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, 86001, United States of America.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Foster
authors.affiliation: Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, 99352, United States of America.
authors.forename: Helen W
authors.initials: HW
authors.lastname: Kreuzer
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007753:Laboratories; D008969:Molecular Sequence Data; D010930:Plague / Q000382:microbiology; D040901:Proteomics; D015010:Yersinia pestis / Q000235:genetics* / Q000472:pathogenicity