title: A multi-omic systems approach to elucidating Yersinia virulence mechanisms.
abstract: The underlying mechanisms that lead to dramatic differences between closely related pathogens are not always readily apparent. For example, the genomes of Yersinia pestis (YP) the causative agent of plague with a high mortality rate and Yersinia pseudotuberculosis (YPT) an enteric pathogen with a modest mortality rate are highly similar with some species specific differences; however the molecular causes of their distinct clinical outcomes remain poorly understood. In this study, a temporal multi-omic analysis of YP and YPT at physiologically relevant temperatures was performed to gain insights into how an acute and highly lethal bacterial pathogen, YP, differs from its less virulent progenitor, YPT. This analysis revealed higher gene and protein expression levels of conserved major virulence factors in YP relative to YPT, including the Yop virulon and the pH6 antigen. This suggests that adaptation in the regulatory architecture, in addition to the presence of unique genetic material, may contribute to the increased pathogenecity of YP relative to YPT. Additionally, global transcriptome and proteome responses of YP and YPT revealed conserved post-transcriptional control of metabolism and the translational machinery including the modulation of glutamate levels in Yersiniae. Finally, the omics data was coupled with a computational network analysis, allowing an efficient prediction of novel Yersinia virulence factors based on gene and protein expression patterns.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, P. O. Box 999, Richland, WA 99352, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Ansong
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Schrimpe-Rutledge
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Mitchell
authors.forename: Sadhana
authors.initials: S
authors.lastname: Chauhan
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.forename: Young-Mo
authors.initials: YM
authors.lastname: Kim
authors.forename: Kathleen
authors.initials: K
authors.lastname: McAteer
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Deatherage Kaiser
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dubois
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brewer
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Frank
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Motin
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Adkins
mesh_terms: D000818:Animals; D001831:Body Temperature; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D018698:Glutamic Acid; D054884:Host-Pathogen Interactions; D008322:Mammals; D008954:Models, Biological; D040901:Proteomics / Q000379:methods*; D005423:Siphonaptera; D059467:Transcriptome / Q000235:genetics*; D014774:Virulence; D015007:Yersinia / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D018698:Glutamic Acid