Targeting Host-Pathogen Synergy in Wound Infection

Wound infections affect between 7% and 15% of hospitalized patients globally. Multiple bacterial species, including Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis are frequently isolated from wounds associated with diabetic foot ulcers, burns, and surgical sites. Polymicrobial wound infections are composed of bacterial biofilms that are more tolerant to antibiotic treatment, compared monomicrobial or non-biofilm infections, leading to more frequent treatment failure. Recent evidence from us and others shows that the mammalian unfolded protein response (UPR) promotes the development of bacterial skin and soft tissue infection (SSTI) and impairs wound healing. Therefore, we hypothesize that UPR activation serves as a synergistic node to promote wound infection. Using a combination of multidisciplinary approaches, we will dissect the mechanisms by which the UPR contributes to polymicrobial wound infections by (1) establishing the role of the UPR in wound healing, (2) determining the contribution of the UPR to bacterial infection and growth in vitro, and (3) interrogating and therapeutically targeting the UPR during polymicrobial infection in vivo. Therapeutic targets for infections and the UPR which currently have none, may have long-term health benefits for Singapore.