Bacteria naturally form a variety of shapes and sizes to survive different environments. This phenomenon is assumed to be important for infection; however, its impact is still largely unknown. One shape change is filamentation; a morphology where bacteria stop dividing and grow into long “spaghetti-like” cells. A number of infections involve bacterial filamentation, including tuberculosis, legionellosis, and the well-studied urinary tract infections (UTIs). UTIs are extremely common, affecting around 150 million people globally every year, with uropathogenic Escherichia coli (UPEC) causing over 80% of these infections. Filamentation is an essential part of the infection cycle of UTIs and filaments have been isolated from the urine of acute and chronic patients. While this morphology has been observed, how it allows UPEC to successfully survive the immune response is not well understood.
Most studies focus on one parameter being important for macrophage engulfment but we studied a range of these with rigorous controls to provide a more holistic view. Employing different antibiotics used to treat UTIs, we have manipulated the size and shape of the UPEC strain UTI89 to study the interaction and responses of live bacteria with THP-1 macrophages. First we used end-point assays to quantify the engulfment ability of macrophages. We found that engulfment is a multifactorial mechanism where bacterial size, shape and surface all matter. We further investigated the interaction between macrophages and filaments using novel microscopy analysis and found that rods and filaments display different engulfment dynamics. We identified that the engulfment of filaments takes longer and is overall less efficient. We are currently performing similar experiments using filaments isolated from a human in vitro bladder model. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial morphology during infections and may provide new ways to prevent or treat these infections.