Dataset Information

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.

SUBMITTER: Kim HS

PROVIDER: S-EPMC4227936 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kim Hye-Sook HS Willett Jonathan W JW Jain-Gupta Neeta N Fiebig Aretha A Crosson Sean S

Molecular microbiology 20141019 4

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. ...[more]

PMID: 25257300

Similar Datasets

Project description:Virulence of pathogenic bacteria is often determined by their ability to adapt to stress.The Brucella abortus general stress response (GSR) system is required for chronic mammalian infection and is regulated by phosphorylation and proteolysis.The B. abortus GSR signaling pathway has multiple layers of post-translational control and is a determinant of chronic infection.This study provides new, molecular level insight into chronic Brucella infection. Brucella spp. are adept at establishing a chronic infection in mammals. We demonstrate that core components of the ?-proteobacterial general stress response (GSR) system, PhyR and ?(E1), are required for Brucella abortus stress survival in vitro and maintenance of chronic murine infection in vivo. ?phyR and ?rpoE1 null mutants exhibit decreased survival under acute oxidative and acid stress but are not defective in infection of primary murine macrophages or in initial colonization of BALB/c mouse spleens. However, ?phyR and ?rpoE1 mutants are attenuated in spleens beginning 1 month postinfection. Thus, the B. abortus GSR system is dispensable for colonization but is required to maintain chronic infection. A genome-scale analysis of the B. abortus GSR regulon identified stress response genes previously linked to virulence and genes that affect immunomodulatory components of the cell envelope. These data support a model in which the GSR system affects both stress survival and the interface between B. abortus and the host immune system. We further demonstrate that PhyR proteolysis is a unique feature of GSR control in B. abortus. Proteolysis of PhyR provides a mechanism to avoid spurious PhyR protein interactions that inappropriately activate GSR-dependent transcription. We conclude that the B. abortus GSR system regulates acute stress adaptation and long term survival within a mammalian host and that PhyR proteolysis is a novel regulatory feature in B. abortus that ensures proper control of GSR transcription.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets