Antimicrobial Drug Discovery
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.