title: Role of the PhoP-PhoQ gene regulatory system in adaptation of Yersinia pestis to environmental stress in the flea digestive tract.
abstract: The Yersinia pestis PhoPQ gene regulatory system is induced during infection of the flea digestive tract and is required to produce adherent biofilm in the foregut, which greatly enhances bacterial transmission during a flea bite. To understand the in vivo context of PhoPQ induction and to determine PhoP-regulated targets in the flea, we undertook whole-genome comparative transcriptional profiling of Y. pestis WT and ΔphoP strains isolated from infected fleas and from temperature-matched in vitro planktonic and flow-cell biofilm cultures. In the absence of PhoP regulation, the gene expression program indicated that the bacteria experienced diverse physiological stresses and were in a metabolically less active state. Multiple stress response genes, including several toxin-antitoxin loci and YhcN family genes responsible for increased acid tolerance, were upregulated in the phoP mutant during flea infection. The data implied that PhoPQ was induced by low pH in the flea gut, and that PhoP modulated physiological adaptation to acid and other stresses encountered during infection of the flea. This adaptive response, together with PhoP-dependent modification of the bacterial outer surface that includes repression of pH 6 antigen fimbriae, supports stable biofilm development in the flea foregut.
authors: 1Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, 99164, USA.
authors: Viveka
authors: V
authors: Vadyvaloo
authors: 2Plague Section, Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
authors: Austin K
authors: AK
authors: Viall
authors: 2Plague Section, Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
authors: Clayton O
authors: CO
authors: Jarrett
authors: 1Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, 99164, USA.
authors: Angela K
authors: AK
authors: Hinz
authors: 3Genomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
authors: Daniel E
authors: DE
authors: Sturdevant
authors: 2Plague Section, Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
authors: B
authors: B
authors: Joseph Hinnebusch
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D005423:Siphonaptera / Q000382:microbiology*; D013312:Stress, Physiological; D015010:Yersinia pestis / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; C061064:PhoP protein, Bacteria