title: Decreased in vivo virulence and altered gene expression by a Brucella melitensis light-sensing histidine kinase mutant.
abstract: Brucella species utilize diverse virulence factors. Previously, Brucella abortus light-sensing histidine kinase was identified as important for cellular infection. Here, we demonstrate that a Brucella melitensis LOV-HK (BM-LOV-HK) mutant strain has strikingly different gene expression than wild type. General stress response genes including the alternative sigma factor rpoE1 and its anti-anti-sigma factor phyR were downregulated, while flagellar, quorum sensing (QS), and type IV secretion system genes were upregulated in the ΔBM-LOV-HK strain vs. wild type. Contextually, expression results agree with other studies of transcriptional regulators involving ΔrpoE1, ΔphyR, ΔvjbR, and ΔblxR (ΔbabR) Brucella strains. Additionally, deletion of BM-LOV-HK decreases virulence in mice. During C57BL/6 mouse infection, the ΔBM-LOV-HK strain had 2 logs less CFUs in the spleen 3 days postinfection, but similar levels 6 days post infection compared to wild type. Infection of IRF-1(-/-) mice more specifically define ΔBM-LOV-HK strain attenuation with fewer bacteria in spleens and significantly increased survival of mutant vs. wild-type infected IRF-1(-/-) mice. Upregulation of flagella, QS, and VirB genes, along with downregulation of rpoE1 and related sigma factor, rpoH2 (BMEI0280) suggest that BM-LOV-HK modulates both QS and general stress response regulatory components to control Brucella gene expression on a global level.
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gourley
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Petersen
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Harms
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA splitter@svm.vetmed.wisc.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Splitter
mesh_terms: D000818:Animals; D058491:Bacterial Load; D017347:Brucella melitensis / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D002006:Brucellosis / Q000382:microbiology / Q000473:pathology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D000071677:Histidine Kinase; D008810:Mice, Inbred C57BL; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D011494:Protein Kinases; D000071677:Histidine Kinase
keywords: LOV; PhyR; brucellosis; flagella; stress; virB