Project Details
Description
Bacterial infections are the most common medical conditions, resulting in considerable economic and public health burdens and substantially affect the life quality of afflicted individuals. Patients suffering from bacterial infections are commonly treated with antibiotics. However, these treatments can result in the development of antibiotic resistance. Therefore, alternative therapies are needed. Vertebrate cells use the cell-autonomous defense programs to monitor infection and to evoke counter responses. Autophagy, the self-eating process for balancing sources of energy at critical times in development and in response to nutrient stress, represents an important innate defense mechanism for control of intracellular pathogens. A common measure for clearing intracellular pathogens involves detection followed by sequestration of pathogen in the autophagosome, a de-novo-generated membrane-bound compartment, which is promptly shuttled to the endolysosome where pathogens are degraded. Because our preliminary data have suggested that two endolysosomal membrane ion channels, BK and TRPML3 regulate autophagosome formation, we hypothesize that TRPML3 and BK increase pathogen clearance by increasing autophagy. We also predict that chemicals promoting TRPML3 and BK activity may combat bacterial infection. To test the hypothesis, we have collaborated with multidisciplinary teams of medical specialists in the fields of autophagy and microbial pathogenesis. We have also collected substantial preliminary data, acquired experience with the proposed work and have been equipped with all the necessary knowledge, space, equipment, techniques and materials that allow us to complete the proposed work. We believe that our study will not only provide important information regarding the role of TRPML3 and BK in autophagy regulation, but also lead to new therapeutic strategies combating many bacterial infections, i.e. developing drugs targeting TRPML3 or BK.
Status | Finished |
---|---|
Effective start/end date | 4/1/18 → 3/31/23 |
Funding
- Institute of Infection and Immunity: US$500,265.00
ASJC Scopus Subject Areas
- Microbiology
- Infectious Diseases
- Immunology