Forced Resurgence and Targeting of Intracellular Uropathogenic Escherichia coli Reservoirs (original) (raw)
Figure 5
UPEC persistence and recurrence within the bladder.
(1) UPEC that gain entry into the bladder lumen can multiply within the urine and in association with the bladder surface. (2) Some bacteria enter host superficial cells and are trafficked into late endosome-like compartments. (3) Shearing forces from the flow of urine, secreted antimicrobial factors, and infiltrating neutrophils can eliminate many bacteria, while internalized UPEC are sheltered. Some intracellular bacteria may enter the host cytosol where they can rapidly multiply, forming IBCs. (4) Infection can induce the exfoliation of the superficial cells, exposing underlying immature BECs (5) that can rapidly differentiate to reestablish barrier function. Chitosan treatment can also stimulate exfoliation of superficial bladder cells and subsequent regenerative processes. Within both the superficial and immature cells of the bladder, UPEC can persist as quiescent reservoirs within membrane-bound compartments enmeshed in F-actin. Antibiotics that can effectively sterilize the urine are ineffective against the intracellular UPEC reservoirs. (6) Redistribution of actin and perhaps other signals associated with terminal differentiation of the BECs may elicit the resurgent growth of UPEC, resulting in bacterial release back into the bladder lumen. By promoting turnover of the urothelium, the intravesical delivery of chitosan can stimulate the resurgence of UPEC from intracellular reservoirs, making the bacteria more accessible to antibiotics.