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Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease

About half of all women will experience urinary tract infections ( UTIs ) in their lifetimes, and despite treatment, about a quarter will develop recurrent infections within six months of initial infection.

A new study at Washington University School of Medicine in St. Louis ( Unites States ) has uncovered a trigger of recurrent UTI infections: a type of vaginal bacteria that moves into the urinary tract.

The research, in mice, is published in PLOS Pathogens.

UTIs most often occur when bacteria that live inside the bowel make their way into the urinary tract. The infections can occur anywhere along the urinary tract but commonly develop in the bladder.
UTIs are treated with antibiotics, but each time a UTI comes back makes it even more likely the infection will recur yet again.

In young, sexually active women, about 80% of UTIs are caused by Escherichia coli. Conventional thinking holds that recurrence occurs when Escherichia coli is reintroduced into the urinary tract.
The new research suggests another way for a subsequent UTI to develop: the vaginal bacterium Gardnerella vaginalis triggers Escherichia coli already hiding in the bladder to cause another UTI.
Gardnerella vaginalis also may be a contributor to more serious, and potentially deadly, kidney infections, the study suggests.

Researchers found that a particular vaginal bacterium, Gardnerella vaginalis, does not cause infection during exposure to the urinary tract, but it damages the cells on the surface of the bladder and caused Escherichia coli from a previous UTI to start multiplying, leading to another bout of disease.

Previous studies already had established that Escherichia coli bacteria can create dormant hiding places for Escherichia coli in the bladder and later be reactivated to cause infection. But this is the first study to identify a plausible trigger.

The reasons why UTIs recur is not fully understood, but the researchers saw a clue in bacterial vaginosis, which is caused by an overgrowth of harmful bacteria, resulting in vaginal odor and discharge.
The condition is associated with UTIs.

As part of the study, the researchers infected the bladders of female mice with Escherichia coli, initiating UTIs, and then let them recover.
One month after infection, no Escherichia coli was detected in the animals' urine. However, previous studies had shown that a small population of Escherichia coli can persist in the bladder at levels undetectable in the urine.

Next, the researchers introduced into the bladders of the mice either Lactobacillus crispatus, a normal vaginal bacterium; Gardnerella vaginalis, which is associated with bacterial vaginosis; or sterile saltwater, as a control.
Both kinds of vaginal bacteria were eliminated from the bladder within 12 hours, but this short sojourn in the bladder was enough for Escherichia coli to reappear in the urine of more than half of the mice exposed to Gardnerella vaginalis, indicating a recurrent UTI.
Mice given the normal vaginal bacteria or sterile saltwater were about five times less likely to develop another UTI compared with those given Gardnerella vaginalis.

Moreover, in some of the mice with Gardnerella vaginalis, bacteria traveled from the bladder up the urinary tract to the kidneys. In women, kidney infections are rare, just 1% of women with bladder infections go on to develop one, but serious.
Kidney infections involve back pain, fever, nausea and vomiting, and can be deadly.

All of the mice that had either Gardnerella vaginalis or Escherichia coli in their urinary tracts showed some degree of kidney damage. But of the mice that had both species, 6% showed severe kidney damage, high levels of Escherichia coli in the kidney and signs that Escherichia coli had moved from the kidney to the bloodstream, a form of UTI that can kill.
In other words, the presence of Gardnerella vaginalis made Escherichia coli more likely to cause severe kidney disease.

The researchers suggest that new clinical studies are needed to inform phisicians treating women for UTIs, especially kidney infections, to look at whether bacterial vaginosis may put some women at greater risk for this severe form of UTI.
Both UTIs and bacterial vaginosis are treatable with antibiotics, but different kinds are required. ( Xagena )

Source: Washington University School of Medicine, 2017