Bacteria, from commensals to pathogens, utilize stress responses to maintain cellular homeostasis in fluctuating environments, enabling cells to survive nutrient deprivation, antibiotic treatments and host defenses. A well conserved key component of the bacterial stress response is the small signaling molecule (p)ppGpp (guanosine tetraphosphate and pentaphosphate). (p)ppGpp can be produced in almost all bacteria to mediate stress resistance and adaptation. (p)ppGpp is also critical for the generation of persister cells that are metabolically dormant and refractory to killing by antibiotics. However, (p)ppGpp regulation in Gram -positive bacteria, including many human pathogens, is poorly understood. The overall rationale of the proposed work is to unravel (p)ppGpp regulation in Gram-positive bacteria, which will provide important insights into the bacterial stress response, antibiotic tolerance, and interactions between microbes and hosts.

Public Health Relevance

We are investigating how Gram-positive bacteria, including many pathogens, use the signaling nucleotide (p)ppGpp for tolerating antibiotic treatment. The proposed study helps us to find strategies to prevent (p)ppGpp-mediated drug tolerance and potentiate the efficacy of antimicrobial treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM127088-03
Application #
9924613
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Reddy, Michael K
Project Start
2018-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Earth Sciences/Resources
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715