Infectious Diseases

Antimicrobial Drug Discovery

Although there is widespread agreement that it is imperative to identify new classes of antibacterial agents, the rate of new antibiotic discovery is unlikely to meet the expected need for the foreseeable future.

With the possible exception of tigecycline, fluoroquinolones were the last class of truly broad-spectrum antimicrobials active against both Gram-positive and Gram-negative bacteria developed in the past 40 years. This rate of discovery is not acceptable given the rapidly increasing prevalence of drug-resistant pathogens.

Antibiotic drug discovery, however, has been limited by numerous obstacles, including the failure to identify new cultivable microorganisms, a high background of toxic compounds or compounds with poor pharmacokinetic properties in synthetic compound libraries, and the inability of most synthetic leads to penetrate across the multi-drug resistance pump barrier of Gram-negative bacteria.

Researchers in our division have bypassed some of these obstacles by developing whole-animal, high-throughput screens that utilize the well-studied nematode Caenorhabditis elegans as a model host to simultaneously identify new classes of antimicrobials with antivirulence or immunomodulatory efficacy and evaluate toxicity and efficacy.