Our Work

Targeting signaling networks that govern biofilm-associated infection

We are studying two-component systems (TCS) in the opportunistic pathogen E. faecalis, which are signal transduction pathways that allow bacteria to sense and respond to changes in their environment. Using a combinatorial CRISPRi tool, we have silenced TCS genes and generated a genetic library to define the complete transcriptional network for each TCS in vitro and determine how each contributes to biofilm formation. Surprisingly, we found that combinatorial silencing of non-cognate RR and HK resulted in attenuated biofilm formation, revealing new insights into TCS cross-talk. We are extending our studies to determine the TCS networks involved in biofilm-associated infections in humans and identifying new therapeutic targets. Additionally, we are investigating the contribution of TCS to gut colonization, post-antibiotic expansion, CAUTI, and wound infections in rodent models. Our goal is to identify druggable targets and small molecule inhibitors to combat E. faecalis infections.