Current treatment of human bacterial infections depends on bactericidal and bacteriostatic antibiotics whose long-term effectiveness is limited by the inevitable development of drug resistance and the potential to devastate the host commensal microbial community, leading to the demise of their effectiveness. An alternative approach to combat bacterial pathogens is the use of anti-infective drugs that selectively disrupt pathways that mediate virulence, such as regulation of pathogenesis genes. Compounds that do not disrupt survival or growth should be less likely to generate resistance than traditional antibiotics. Ideally, these reagents should not disrupt bacterial and host metabolism, and should not cause harmful side effects.

In simpler terms, the human body actually contains more microbial cells than mammalian ones. We naturally live in peaceful, mutually beneficial coexistence with these organisms. Trouble arises when this balance is disrupted and those microbial organisms that possess harmful characteristics begin to proliferate. Antibiotics are designed to kill microbes indiscriminately. Whereas, anti-infectives are not designed to kill microbes but rather to prevent the expression of their harmful features.

Our Lab has identified and validated the utility of selective anti-infective compounds that efficiently inhibited the synthesis of molecules required for the activation of the MvfR-dependent QS regulatory pathway of the human opportunistic pathogen Pseudomonas aeruginosa. Such reagents should have significant clinical utility in treating acute and chronic P. aeruginosa infections. In addition, several of these compounds could have a broad-spectrum anti-bacterial effect against several clinically significant human pathogens.

Our group has also identified a series of novel compounds that typify the properties of anti-infectives. Part of these compounds limit infection (P. aeruginosa) by acting upon host cellular, physiological and/or metabolic functions. As some of these compounds modulate key immune functions also important in defense against other Gram-negative bacterial pathogens, they will likely be efficacious against a broader number of pathogenic bacteria.