In order for disease to result from bacterial infection, the expression of a series of genes must occur, allowing the prospective pathogen to adapt to the hostile environment in the host. Because this gene expression contributes to the virulence of the pathogens, the products encoded by the genes are referred to as "virulence factors." These factors contribute to the microorganism's ability to survive and grow at the site of the infection.

According to Hoch, "Impairment of one or more of these virulence factors by mutation, antibody neutralization or chemical inhibition can be the determining factor in tipping the outcome of the infection favorably toward the host. As a consequence, we are gaining an appreciation for the potential usefulness of bacterial virulence factors as new targets for therapeutic intervention against antimicrobial resistant pathogens. Two-component signal transduction systems are the only common regulatory elements shared by a wide range of virulence systems, raising the possibility that a broad spectrum inhibitor to such elements may suppress virulence in a variety of microorganisms."

This study shows the efficacy of the compound RWJ-49815 and its derivatives as the first series of inhibitors of two-component systems with demonstrated bactericidal activity against a broad range of microorganisms. The scientists are hopeful that these inhibitors targeting the signal transduction mechanisms will be useful new tools in the armamentarium against infectious disease. They speculate that human clinical trials could begin in two to three years.

Funding for the study was made possible by Johnson & Johnson and the National Institutes of Health.

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Contact: Robin B. Goldsmith
rgoldsmi@scripps.edu
(619) 784-8134
Scripps Research Institute
28-Apr-1998