title: The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signalling pathway.
abstract: In the intracellular pathogen Brucella abortus, the general stress response (GSR) signalling system determines survival under acute stress conditions in vitro, and is required for long-term residence in a mammalian host. To date, the identity of the Brucella sensor kinase(s) that function to perceive stress and directly activate GSR signalling have remained undefined. We demonstrate that the flavin-binding sensor histidine kinase, LovhK (bab2_0652), functions as a primary B. abortus GSR sensor. LovhK rapidly and specifically phosphorylates the central GSR regulator, PhyR, and activates transcription of a set of genes that closely overlaps the known B. abortus GSR regulon. Deletion of lovhK severely compromises cell survival under defined oxidative and acid stress conditions. We further show that lovhK is required for cell survival during the early phase of mammalian cell infection and for establishment of long-term residence in a mouse infection model. Finally, we present evidence that particular regions of primary structure within the two N-terminal PAS domains of LovhK have distinct sensory roles under specific environmental conditions. This study elucidates new molecular components of a conserved signalling pathway that regulates B. abortus stress physiology and infection biology.
authors.affiliation: The Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA; Howard Taylor Ricketts Laboratory, University of Chicago, Argonne National Laboratory, Argonne, IL, USA.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Willett
authors.forename: Neeta
authors.initials: N
authors.lastname: Jain-Gupta
authors.forename: Aretha
authors.initials: A
authors.lastname: Fiebig
authors.forename: Sean
authors.initials: S
authors.lastname: Crosson
mesh_terms: D000143:Acids / Q000633:toxicity; D000818:Animals; D002003:Brucella abortus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002006:Brucellosis / Q000382:microbiology; D002460:Cell Line; D004195:Disease Models, Animal; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D006801:Humans; D051379:Mice; D050296:Microbial Viability; D009000:Monocytes / Q000382:microbiology; D016877:Oxidants / Q000633:toxicity; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013312:Stress, Physiological; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000143:Acids; D016877:Oxidants; D037521:Virulence Factors; D011494:Protein Kinases; D000071677:Histidine Kinase