Deciphering Novel Mechanisms of Antimicrobial Resistance with Massively Parallel Combinatorial Genetics

Abstract

Antibiotic resistance is a rapidly growing problem at the global scale. The pace of antimicrobial discovery is not keeping pace with the evolution of resistance by bacteria against antibiotics. As a result, our existing antibiotic arsenal is dwindling and new approaches to discover effective antimicrobial agents to treat bacterial pathogens are urgently needed. To address this threat, we are pursuing multiple complementary strategies for the development of novel antimicrobials. First, we are searching for combinatorial therapies to target pathogenic bacteria. This strategy is predicated on the idea that combining multiple drugs together could enhance the net antimicrobial activity. To do so, we are using a high-throughput platform to screen for drug and target combinations with antimicrobial effects. Second, we are exploring alternative antimicrobials, including bacteriophage and antimicrobial peptides, as targeted therapeutic agents that be rapidly adapted to treat emerging bacterial infections. Third, we are creating technologies to improve the discovery and production of natural metabolites from bacteria, which may be useful as new chemical matter for development of antimicrobials and other drugs. We anticipate that these multiple therapeutic approaches will aid in combating antimicrobial resistance.

Document Details

Document Type
DoD Grant Award
Publication Date
May 26, 2016
Source ID
HDTRA11510050

Entities

People

  • Timothy K. Lu

Organizations

  • Defense Threat Reduction Agency
  • Harvard University

Tags

Readers

  • Microbial Pathology
  • Oncology (Cancer Research).
  • Systems Analysis and Design

Technology Areas

  • Biotechnology