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Possible New Trigger for Recurrent Urinary Tract Infections Identified

Researchers have identified a naturally occurring component of the vaginal microbiota as a possible trigger of recurrent UPEC UTI and a subsequent kidney infection.

A current model of the “infection life cycle” for UPEC-caused UTIs starts with acute infection, in which UPEC attach to and invade cells lining the bladder. There, they are protected from immune responses and form intracellular bacterial communities (IBCs), expand in number, and then burst forth from the bladder cells. As the bladder tries to clear the bacteria by sending out immune cells and sloughing off the superficial layer of infected bladder cells, remaining UPEC go deeper within the bladder tissue and form additional IBCs, contributing to the acute infection. In some cases, these IBCs, which are also protected from antibiotics, go on to exist in a quiescent state (latency) until a signal in the environment causes them to emerge and start a new infection. Together with other evidence, such as the detection of IBCs in human urine during infection, this model provides a possible explanation for some of the cases in which recurring UTIs in humans are caused by the same bacterial strain—complementing other likely sources of same-strain reinfection, such as the gastrointestinal tract and vagina. However, factors that can trigger the emergence of quiescent UPEC from intracellular reservoirs in humans remain unknown.

Building on evidence implicating vaginal bacteria in susceptibility to bladder and kidney infections, researchers sought to determine if certain bacteria might trigger recurrent UPEC infection. Using a female mouse model carrying latent UPEC reservoirs, they exposed bladders of these mice to one or the other of two different types of bacteria that can predominate in the vagina, providing two doses one week apart. They found that in the case of one of the bacteria, Gardnerella vaginalis (G. vaginalis), this transient exposure was sufficient to induce the appearance of UPEC in the urine of over 50 percent of the tested mice. Notably, mice that responded to G. vaginalis as a trigger for UPEC reemergence were more likely to have had a more severe UTI prior to its resolution. G. vaginalis is associated with bacterial vaginosis, a form of inflammation caused by bacterial overgrowth. Many risk factors for bacterial vaginosis in humans overlap with risk factors for kidney infection. Upon examination, the researchers found that G. vaginalis was detectable in about one-third of mouse kidneys within 3 hours of exposure, and was able to cause kidney injury in the absence of E. coli. Exposure of UPEC reservoir-containing mice to G. vaginalis also increased the risk for these animals to develop severe E. coli kidney infections. This result suggests that G. vaginalis is a trigger for recurrent UTIs in mice, and future studies could help delineate whether G. vaginalis exposure is also a trigger for recurrent UTIs in humans, and the potential relevance to clinical care and prevention of UTIs and possibly associated kidney infections.

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