Synthesis and Chararterization of Therapeutics for the Modulation of Bacterial Virulence

Acute infectious diseases pose significant problems which include the potential failure of antimicrobial therapy and the serious sequelae that may result. These treatment failures may occur due to a lack of diagnostic information during early onset of the disease, resulting in the use of the incorrect antibiotic or antimicrobial resistance, and the inadequacy of current therapy for ameliorating sequelae. While it is expected that virulence responses of pathogenic microorganisms to host-specific signals play a role in disease, little information is available to utilize in designing novel intervention therapies. The identification of the environmental cues that regulate bacterial virulence should provide a basis to develop approaches to inhibiting pathogenic processes and result in therapeutics for modulating pathogenesis. This Phase I effort will be directed toward the synthesis and in vitro characterization of compounds to modulate (decrease) the expression of virulence factors by pathogenic bacteria. Antex Biologics through the use of its proprietary Nutriment Signal Transduction Technology (NST) has identified specific host enhancers that increase expression of virulence factors by bacterial pathogens. Using analogue chemistry, compounds (anti-enhancers) will be identified to decrease the expression of bacterial virulence.