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MECHANISMS OF SIGNAL TRANSDUCTION IN BRUCELLA

Investigators
Crosson, Se, .
Institutions
Michigan State University
Start date
2020
End date
2025
Objective
The overarching goal of this research program is to develop a mechanistic understanding of molecular connections between environmental stress adaptation and animal infection by a group of bacteral zoonotic pathogens known as Brucella. We have previously shown that the general stress response (GSR) signaling system controls stress adaptation and chronic infection in a mammalian model of disease. We are now working to understand how B. abortus (a bovine pathogen) and B. ovis (an ovine pathogen) integrate multiple environmental signals via a set of HWE-family histidine kinases to influence animal infection. Specifically, we have preliminary evidence that two sensor kinases form a complex that coordinately controls GSR activation and infection in B. abortus. We have further discovered that previously uncharacterized genes regulated by the GSR system - eipB, gsrN1 and gsrN2 - are determinants of successful mammalian infection. These genes protect Brucella spp. from cell envelope stress and control stress-dependent gene expression at the post-transcriptional level, respectively.Our multi-disciplinary investigation of these genes will define the mechanistic underpinnings of infection in bacterial pathogens of significant agricultural and human health import. Moreover, the experiments proposed herein have the potential to inform new treatments for α-proteobacterial disease such as brucellosis. Specific goals/objectives of this project are:Define the mechanism of stress signal integration by Brucella HWE-family sensor kinasesCharacterize the molecular basis by which EipB ensures Brucella cell envelope integrityDetermine the mechanism by which the small RNAs GsrN1 and GsrN2 regulate Brucella infection biology
Funding Source
Nat'l. Inst. of Food and Agriculture
Project source
View this project
Project number
MICL02671
Accession number
1022703
Categories
Sanitation and Quality Standards