Department of Microbiology & Immunology Seminar
Speaker: Dr. Jose L. Lopez-Ribot
Professor and Margaret Batts Tobin Distinguished Chair, Department of Molecular Microbiology & Immunology, Associate Director, South Texas Center for Emerging Infectious Diseases, Associate Dean for Research and Graduate Studies, College of Sciences, The University of Texas at San Antonio, San Antonio
Title: “Inhibitors of Filamentation and Biofilm Formation as New Anti-virulence Agents Against Candida albicans Infections”
The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, an increasingly frequent infection in immuno- and medically-compromised patients. The high morbidity and mortality associated with C. albicans infections, coupled with the emergence of drug resistance demand the development of novel therapeutic strategies. However, there is a paucity of selective targets that can be exploited for the development of new antifungal agents. Contrary to conventional antibiotics that kill or curtail growth, specifically targeting pathogenic mechanisms represents an attractive option, yet clinically unexploited, for antifungal drug development. In C. albicans, a growing body of research over the last few decades has provided important insights into its virulence factors and their contribution to the pathogenesis of candidiasis. Filamentation and biofim formation are two of the main virulence factors, and as such they represent high value targets for the development of novel anti-virulence approaches against C. albicans infections. To this end our group has performed large-scale phenotypic screenings of over 50,000 drug-like small molecule compounds to identify inhibitors of these two biological processes. After confirmation of the initial hits identified during these screens, two were selected as our leading compounds for further characterization. This presentation will discuss their in vitro and in vivo properties. Overall our results provide proof of concept for the implementation of anti-virulence approaches against C. albicans infections, including those refractory to treatment with conventional antifungal agents, which will also be less likely to foster the emergence of resistance.