Fig 1.
A model of C. difficile biofilms during infection.
C. difficile initially attaches to the mucosal layers in the gut, when the native gut microbiota is disrupted by broad spectrum antibiotics. Increased c-di-GMP levels resulting in decreased bacterial motility enables attachment and establishment of microaggregates or communities. These communities could exist as single species or in close association with the gut microbiota, serve as a niche for production of spores and toxins (toxins A, B, and binary C. difficile toxin), and provide protection from oral antibiotics using for treatment (e.g., vancomycin, metronidazole) in the lumen. Surface factors (e.g., pili, flagella, S-layer), quorum sensing (e.g., LuxS), and regulators (e.g., Spo0A, CD630_2214) control biofilm/aggregate formation. Direct bacterial interactions of C. difficile and action of toxins trigger cell death and disruption of epithelial barrier, allowing bacteria to penetrate the epithelial cell layer to the underlying basement membrane and myofibroblasts. C. difficile may form communities in underlying tissue which may protect bacteria from oxygen and immune responses. Bacterial communities in the gut mucosa may allow bacterial persistence, and under conducive conditions, bacteria may be dispersed, leading to reseeding and recurrence of infection. Image created with BioRender.com.