More
than 60% of women will experience a urinary tract infection (UTI) at some point
in their lives, and about a quarter will get a second such infection within six
months, for reasons that have been unclear to health experts.
Now,
researchers at Washington University School of Medicine in St. Louis have
discovered that an initial infection can set the tone for subsequent
infections. In mouse studies, the researchers found that a transient infection
triggers a short-lived inflammatory response that rapidly eliminates the
bacteria. But if the initial infection lingers for weeks, the inflammation also
persists, leading to long-lasting changes to the bladder that prime the immune
system to overreact the next time bacteria find their way into the urinary
tract, worsening the infection.
To
understand why some people are more prone to severe, recurrent infections than
others, Hannan and co-senior author Scott J. Hultgren, PhD, the Helen L.
Stoever Professor of Molecular Microbiology -- along with co-first authors Lu
Yu, PhD, and Valerie O'Brien, PhD, both graduate students when the work was
conducted -- infected a strain of genetically identical mice with E. coli, the
most common cause of UTIs in people. The strain can have widely divergent
responses to bacterial bladder infections. Some eliminate the bacteria within a
few days; others develop chronic infections that last for weeks.
The
researchers infected these mice with E. coli, monitored them for signs of
infection in their urine for four weeks, and then gave them antibiotics. After
giving the mice a month to heal, the researchers infected them again. For
comparison, they also infected a separate group of mice for the first time.
All
the previously infected mice mounted immune responses more rapidly than the
mice infected for the first time. The ones that had cleared the infection on
their own the first time around did so again, eliminating the bacteria even
faster than before. But the mice that failed to clear the infection the first
time did much worse, despite the speed of their immune responses. A day after
infection, 11 out of 14 had more bacteria in their bladders than they had
started with, and many went on to again develop chronic infections that lasted
at least four weeks.
To find out, the researchers
took mice that had recovered from initial prolonged UTIs and depleted their
TNF-alpha before re-infecting them with bacteria. Without TNF-alpha driving
excessive inflammation, the mice fared better, significantly reducing the
number of bacteria in their bladders within a day of infection.
The
findings suggest that targeting TNF-alpha or another aspect of the inflammatory
response that causes bladder tissue damage during acute infection may help
prevent or alleviate recurrent UTIs, the researchers said.
See:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
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