Bladder cells can physically eject Escherichia coli, which cause urinary tract infections (UTIs), according to a new study published in the June 4, 2015, edition of Cell. The finding suggests that capitalizing on this natural tendency of bladder cells might help treat patients with recurrent UTI.
UTIs, the majority of which occur in women, account for nearly 8.1 million doctor visits every year. Bacterial infections are the most common cause of UTIs, and 70% of infections arise from a particular strain of E coli.
“Because E coli are able to hide inside the bladder cells, it’s especially difficult to treat UTIs with regular antibiotics," explains Soman N. Abraham, a researcher at Duke Medicine. "So there is increased need to find new strategies for treatment, including co-opting any preexisting cellular tactics to combating infection.”
When E coli first attack bladder cells, autophagy is the first line of defense. The autophagy machinery encases the bacteria in a host membrane that moves to the lysosome that destroys harmful pathogens in its acidic environment. However, after they enter the lysosome, some pathogens can neutralize the acidic environment and avoid being degraded.
Using mouse models of UTIs and cultured human bladder cells, the study authors found that the host cells can sense when lysosomes have been rendered neutral and are malfunctioning. The host cells then respond by triggering the lysosome to eject its contents, including the bacteria.
“When the cells have trouble digesting the materials in the lysosomes, a logical way to get rid of this potential hazard is to throw it up,” says first author Yuxuan Miao, a PhD candidate in Duke’s department of molecular genetics and microbiology.
The bacteria expelled from the bladder cells appear to be encased in a cell membrane, which presumably ensures urinary elimination and stops the bacteria from reattaching to the bladder wall.
“It was previously thought that lysosomes always degrade their contents," Miao observes. "Here we are showing for the first time that, when the contents cannot be degraded, the lysosome appears to have a back-up plan, which is to expel the contents in capsules.”
The researchers hope these findings will help others discover chemical targets to accelerate and amplify the ability of bladder cells to expel bacteria.
“Many women tend to experience recurrent infections once they have an initial bout of UTI,” Abraham says. “The reason for this is that there is bacterial persistence within the cells of the bladder. If we can eliminate these reservoirs using agents that promote expulsion, then we can potentially eradicate recurrent UTIs.”
In addition to Abraham and Miao, study author Guojie Li is also a member of Duke Medicine; other study authors include Xiaoli Zhang and Haoxing Xu from the University of Michigan.