Revisiting the Escherichia coli polysaccharide capsule as a virulence factor during urinary tract infection: Contribution to intracellular biofilm development

Abstract

The treatment of urinary tract infections (UTIs) is becoming increasingly challenging as uropathogenic Escherichia coli (UPEC) becomes more resistant to the most widely prescribed oral antibiotics.  The treatment of UTIs may also be complicated by the inherent lifestyle of UPEC in the urinary tract, revealed in recent studies demonstrating bacterial invasion into bladder epithelial cells, the formation of intracellular bacterial communities (IBCs; biofilm-like colonies in the host cell cytosol), and chronic intracellular persistence with subversion of normal immune surveillance.  Identifying key targets in the pathogenesis of UTIs, including IBC formation, will be crucial to replenish the arsenal of treatments for UTIs.  Focused on elucidating bacterial components that underpin the development of IBCs, Anderson et al. recently demonstrated a novel role for the K capsule polysaccharide in IBC formation.  Without K capsule, intracellular UPEC failed to undergo normal IBC formation, the intracellular bacteria failed to preclude neutrophil infiltration, and UPEC did not undergo serial cycles of intracellular proliferation, resulting in attenuation of the infection.  This study also demonstrated an interconnection between sialic acid homeostasis and IBC formation, demonstrating a unique role for this amino sugar in biofilm formation.  This study provides evidence for an expanded role for K capsule in the intracellular and extracellular pathogenesis of UTI, and provides additional rationale for the development of small molecule inhibitors of capsule biogenesis as anti-virulence therapeutics.