Emerging antibiotic resistance is a global health crisis. From broadly resistant superbugs to extremely drug resistant Mycobacterium tuberculosis (XDR-TB), the specter of untreatable bacterial infection has become an alarming reality. The problem has become so acute that President Barack Obama recently issued an executive order calling multidrug resistant bacteria a national security priority. Likewise, the need to develop better antibiotics that shorten the treatment time to cure persistent bacterial infections also remains a major goal, especially for some of the most notorious pathogens of man, including M. tuberculosis. Due to the slow rate of new antibiotics emerging from the lab, countering antibiotic resistance and persistence by modifying existing drugs or developing inhibitors to new bacterial targets is unlikely to keep up with the increasing demand. The goal of this project is to take a radically different approach to new antibiotic development by identifying small molecules that target powerful host immune pathways of innate immune cells, creating adjunctive therapies that will synergize with conventional antibiotics. This approach is antithetical to traditional antibiotic development programs, which seek to identify molecular inhibitors that target essential pathways of the bacterium but avoid host pathways. The potential impact of Host-Directed Therapies (HDTs) could be dramatic, as they may re-sensitize drug-resistant strains and shorten the time to eradicate chronic infections. In particular, this proposa seeks to translate our understanding of host-pathogen interactions into a novel program for identifying small molecules targeting host processes that will synergize with traditional antibiotics during TB infection. The implications of success may extend beyond bacterial infection, as this approach could have huge implications for a broad range of infectious agents, and even boost vaccine efficacy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1AI124619-04
Application #
9319155
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lacourciere, Karen A
Project Start
2015-09-30
Project End
2020-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704