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: Christopher R Gourley, Erik Petersen, Jerome Harms, Gary Splitter
• Journal: Pathogens and disease (Pathog Dis) Vol. 73 Issue 2 Pg. 1-8 (Mar 2015) ISSN: 2049-632X [Electronic] United States
• PMID: 25132657 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © FEMS 2014. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Virulence Factors
• Protein Kinases
• Histidine Kinase

Topics

• Animals
• Bacterial Load
• Brucella melitensis (enzymology, genetics, growth & development)
• Brucellosis (microbiology, pathology)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation, Bacterial
• Gene Knockout Techniques
• Histidine Kinase
• Mice, Inbred C57BL
• Protein Kinases (deficiency, metabolism)
• Spleen (microbiology)
• Survival Analysis
• Virulence
• Virulence Factors (deficiency, metabolism)