A string of bad luck: the role pf bacterial filamentation in response to the antimicrobial peptide LL-37

Candidate: Madison Tomlinson

Supervisors: Dr. Roberto Botelho and Dr. Joseph McPhee

Abstract:

Urinary tract infections (UTIs) are one of the most common bacterial infections in humans. Uropathogenic E. coli (UPEC) are the primary cause of UTIs. During a UTI, UPEC invades bladder  epithelial cells forming intracellular biofilm-like structures with heterogenous bacterial  morphologies, including filamentous. These infections often persist despite the host immune system. In this study, we examine filamentation in E. coli K12 and UPEC strains and test whether filamentous cells exhibit altered resistance to immune responses. Utilizing fluorescent microscopy, we demonstrate that filamentation increases bacterial survival against the  antimicrobial peptide, LL-37, and slows engulfment by macrophage phagocytosis with subsequent increased survival within macrophages. We also established LL-37 localization in E. coli and determined that LL-37 localizes differently to filaments. This work demonstrates that filamentation is an adaptive response to host induced stress that allow UPEC to better survive, suggesting that interference with filamentation might be a viable approach to treat UTIs.