LOV Histidine Kinase Modulates the General Stress Response System and Affects the virB Operon Expression in Brucella abortus

PLoS One. 2015 May 19;10(5):e0124058. doi: 10.1371/journal.pone.0124058. eCollection 2015.

Abstract

Brucella is the causative agent of the zoonotic disease brucellosis, and its success as an intracellular pathogen relies on its ability to adapt to the harsh environmental conditions that it encounters inside the host. The Brucella genome encodes a sensor histidine kinase containing a LOV domain upstream from the kinase, LOVHK, which plays an important role in light-regulated Brucella virulence. In this report we study the intracellular signaling pathway initiated by the light sensor LOVHK using an integrated biochemical and genetic approach. From results of bacterial two-hybrid assays and phosphotransfer experiments we demonstrate that LOVHK functionally interacts with two response regulators: PhyR and LovR, constituting a functional two-component signal-transduction system. LOVHK contributes to the activation of the General Stress Response (GSR) system in Brucella via PhyR, while LovR is proposed to be a phosphate-sink for LOVHK, decreasing its phosphorylation state. We also show that in the absence of LOVHK the expression of the virB operon is down-regulated. In conclusion, our results suggest that LOVHK positively regulates the GSR system in vivo, and has an effect on the expression of the virB operon. The proposed regulatory network suggests a similar role for LOVHK in other microorganisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brucella abortus / enzymology
  • Brucella abortus / genetics*
  • Genes, Bacterial*
  • Histidine Kinase
  • Operon*
  • Protein Kinases / metabolism*
  • RNA, Bacterial / isolation & purification
  • Stress, Physiological*
  • Two-Hybrid System Techniques

Substances

  • RNA, Bacterial
  • Protein Kinases
  • Histidine Kinase

Grants and funding

This work was supported by Agencia Nacional de Promoción Científica (www.agencia.mincyt.gob.ar) grant PICT-2011-2672 to FAG, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)(www.conicet.gov.ar) PIP-2012 to GP and National Science Foundation (www.nsf.gov) 0843617 to WRB. FAG and GP are researchers of CONICET. GS is recipient of a fellowship of CONICET. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.