Sarah Comer

Biofilms are multicellular communities of bacteria that can form on both biotic and abiotic surfaces. Biofilms are particularly challenging to eliminate, as they are encased by a matrix of extracellular polymeric substances (EPS) making them resistant to antibiotic penetration and enabling evasion of the immune response. Given their robust nature, biofilms contribute to several types of infections including urinary tract infections (UTIs). Thus, there is a need to develop novel therapies targeting biofilms.

Previous work in the Hadjifrangiskou lab has focused on characterizing biofilms that form during bladder infection, by uropathogenic Escherichia coli (UPEC), the leading cause of UTIs. Previous studies determined that UPEC respire aerobically during biofilm expansion in the bladder. This led to the investigation of the terminal quinol oxidases of the electron transport chain. E. coli encodes three quinol oxidases: one heme copper oxidase, cytochrome bo, and two bd-type oxidases, cytochrome bd and cytochrome bd2. The oxidases support respiration by coupling electron transfer from quinol to molecular oxygen with the generation of a proton motive force (pmf) that is used for ATP production. Recent work determined that loss of cytochrome bd altered UPEC biofilm architecture, enhanced susceptibility to antibiotics, and rendered the mutants immotile. This occurred despite compensatory expression of cytochrome bo and without defects in flagellar assembly. The defect in motility was attributed to reduction of respiratory flux in the mutants, which occurred without affecting ATP production. Therefore, the current hypothesis is that in addition to its role in respiration, the pmf generated by cytochrome bd can energize other processes like motility. My project aims to address this by 1) determining the mechanism of how cytochrome bd influences motility and 2) evaluating the potential of fungal products that inhibit cytochrome bd as adjuvants to current antibiotics.

Mentor: Maria Hadjifrangiskou, Ph.D.