title: Reprogramming of Yersinia from virulent to persistent mode revealed by complex in vivo RNA-seq analysis.
abstract: We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umea University, Umeå, Sweden.
authors.forename: Kemal
authors.initials: K
authors.lastname: Avican
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Fahlgren
authors.affiliation: Science for Life Laboratory, Royal Institute of Technology, Solna, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Huss
authors.affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Ann Kathrin
authors.initials: AK
authors.lastname: Heroven
authors.affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Beckstette
authors.affiliation: Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Dersch
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden; Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umea University, Umeå, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Fällman
mesh_terms: D000818:Animals; D002432:Cecum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D051379:Mice; D046228:Microarray Analysis; D064307:Microbiota / Q000276:immunology; D012329:RNA, Bacterial / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*; D014774:Virulence / Q000235:genetics*; D015011:Yersinia pseudotuberculosis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D015012:Yersinia pseudotuberculosis Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D012329:RNA, Bacterial