Staphylococcus aureus is a leading cause of human morbidity and mortality, causing infection of the skin and soft tissues, post-surgical wounds, and lung infection among influenza and cystic fibrosis patients. Widespread multi-drug resistance has made eradication of S. aureus increasingly challenging, necessitating a deeper understanding of the physiology and pathogenesis associated with these organisms. A key aspect of bacterial survival and adaptation to altered environmental conditions is the ability to rapidly alter cellular behavior through second messenger signal transduction. C-di-AMP has recently emerged as a key regulator of bacterial physiology, pathogenesis, and immune activation. In the context of S. aureus, we believe that c- di-AMP produced by S. aureus has three important roles; (i) as a signaling molecule that mediates S. aureus metabolism and antibiotic resistance, (ii) as a bacterial PAMP that promotes pathological inflammation and host susceptibility to bacterial infection, and (iii) as a mediator of inter-bacterial signaling that alters the outcome of co-infections. Findings from these studies may have significant impacts on the course of antibiotic therapy during S. aureus infection and may uncover a novel target to eradicate recalcitrant S. aureus and the inflammation itpromotes.

Public Health Relevance

Staphylococcus aureus is a leading cause of human disease and is becoming increasingly recalcitrant to antibiotic treatment. By characterizing the mechanisms that contribute to S. aureus growth and pathogenesis, we aim to identify new targets for therapeutic intervention of many chronic and acute infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI139071-01A1
Application #
9736375
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Huntley, Clayton C
Project Start
2019-02-01
Project End
2024-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Washington
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195