The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signaling pathway

The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signaling pathway

Summary

In the intracellular pathogen Brucella abortus, the general stress response (GSR) signaling 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 signaling have remained undefined. We demonstrate that the flavin-binding sensor histidine kinase, LovhK (bab2_0652), functions as a primary B. abortus GSR sensor. LovhK efficiently 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 signaling pathway that regulates B. abortus stress physiology and infection biology.

Kim, H.-S. Willett, J.W. Jain-Gupta, N., Fiebig, A. and Crosson, S. 2014. The Brucella abortus virulence regulatorLovhK, is a sensor kinase in the general stress response signaling pathway.  Mol. Microbiol. doi: 10.1111/mmi.12809.

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