THE ROLE OF BACTERIAL FILAMENTATION IN THE PROTECTION AGAINST ANTIMICROBIAL PEPTIDE LL-37

Candidate: Natasha Porco
Supervisor: Dr. Roberto Botelho and Dr. Joseph McPhee  

ABSTRACT

Urinary tract infections (UTIs) are one of the most common types of bacterial infection. Uropathogenic E. coli (UPEC) is the most common cause of UTIs. During a UTI, bacteria ascend the urethra before surface colonization and entry of bladder epithelial cells by UPEC. Bacteria then enter epithelial cells and replicate, forming intracellular bacterial communities (IBCs). As part of the innate immune response against UTIs, LL-37 is released by neutrophils and epithelial cells to modulate host-immunity and elicit bacterial lysis through membrane interactions. In this study we use fluorescent microscopy of single cells to demonstrate that LL-37 specifically targets and eliminates actively dividing cells, initiating cell death at the bacterial divisome. Notably, this killing effect occurs in the late stages of the cell division process, following the recruitment, activation, and disassembly of FtsN from the divisome. Additionally, our findings indicate that various mechanisms of bacterial filamentation contribute to E. coli's reduced susceptibility to LL-37-induced killing. Although the mechanism behind division-mediated sensitization remains poorly understood, gaining insights into this phenomenon holds the potential to provide fundamental knowledge about how bacteria evade innate immune responses. Furthermore, it may pave the way for identifying novel targets for the treatment of urinary tract infections.