About
The research in our laboratory focuses on the characterization of virulence factors in the opportunistic fungal pathogen Candida albicans and on analyzing the factors that play a role in the transition between colonization and infection. We have several ongoing projects pursuing different aspects of Candida pathogenesis including biofilm formation, drug resistance and fungal-bacterial interactions in biofilm. Our studies have focused on studying the interactions between C. albicans and the bacterial species Staphylococcus aureus, the most commonly co-isolated human pathogens largely due to their ability to adhere to biotic and abiotic surfaces. Biofilm-related polymicrobial infections are typically associated with the presence of catheters and indwelling medical devices. By taking various approaches, our in vitro and in vivo studies have provided strong evidence indicating a strong affinity between these diverse species impacting biofilm development, drug tolerance and evasion of host immune factors. We are currently studying the clinical and therapeutic implications of their synergistic interaction using a clinically relevant mouse subcutaneous catheter model to study in vivo-grown mixed biofilms. Through dissecting the regulatory and transcriptional pathways uniquely expressed during co-infection, we aim to identify microbial phenotypes of enhanced pathogenic potential central to the persistence and enhanced drug tolerance of biofilm co-infections. The overall goal of this project is to identify novel therapeutic strategies targeting complex polymicrobial infections.
We are also investigating the role of host oral innate immunity, specifically the salivary antifungal peptide histatin-5, in protection of the oral cavity against C. albicans colonization. As oral candidiasis is the most prevalent opportunistic infection in HIV+ individuals, we hypothesize that decreased histatin-5 salivary levels play a key role in the enhanced predisposition of this patient population to oral candidiasis. In this project, using prospective clinical studies, we aim to define a novel mechanism behind the prevalence of oral candidiasis in these vulnerable individuals. In light of the increasing emergence of C. albicans strains resistant to the common antifungals, antimicrobial peptides have gained considerable attention as alternate therapeutics and specifically histatin-5. We recently developed the first pharmaceutically viable bioadhesive hydrogel formulation of histatin-5 (under patenting) designed for oral topical application for the prevention and treatment of oral candidiasis. The efficacy of the novel formulation was demonstrated in vivo in our mouse model of oral candidiasis. Currently, we are developing mouse models of periodontal disease and wound healing in order to explore the anti-inflammatory and tissue regeneration properties of the new formulation.
Recent studies have reported high prevalence for the cariogenic bacterial species Streptococcus mutans in dental biofilms where C. albicans resides, suggesting that this fungal-bacterial interaction may mediate development of dental caries. Therefore, another ongoing project in our laboratory is to investigate the co-adherence and co-colonization of these species in vitro and in vivo within the context of dental caries development.
