- Urinary tract infections
(UTIs) are one of the commonest reasons for hospital visits.
- Nearly 80 percent of
UTIs are caused by E. coli
- Newprotein in E.
coli identified, that may enable persistence of infection.
- Targeting this protein
may help treat or prevent chronic infection.
protein present in urinary tract infection (UTI)
causing bacteria, primarily E. coli may be responsible
for persistence of the bacteria in the urinary bladder, and causing chronic
infections. Researchers have identified
this protein, and also succeeded in vaccinating mice against this protein,
finding that it reduced the incidence of severe UTIs.
Why Many UTIs Become
‘Discovery of new bacterial protein may open up new options to treat and prevent urinary tract infections (UTIs).’
Once the bacteria gain entry into the bladder, the bacteria attach to
the bladder wall by means of long hair like projections pili which serve as
organs of attachment. This prevents their being swept away by the urinary
stream, enabling them to establish infection in the urinary tract in its
initial stages. A team of scientists have now identified a second pilus, called Fml
, with genes that are remarkably similar to
the type 1 pilus but whose function was
This study focused on the role of these pili in causing severe or
chronic infections, and whether this knowledge could be used for therapeutic
Details of The Study
As part of the present study, Hultgren, postdoctoral researcher Matthew
Conover, PhD, colleagues Ségolène Ruer, PhD, and Han Remaut, PhD, of Vrije
Universiteit Brussel in Belgium, and others proceeded to find out the function
of the Fml pilus. They focused their attention on a protein known as FmlH, which they thought was located at the tip of
the pilus, since it would help bacteria attach easily to the bladder wall
The scientists removed the gene for FmlH from some of the E. coli and
then infected the urinary tracts of mice with bacteria having the FmlH gene,
and others deficient in the gene. They discovered that E. coli deficient in
FmlH were less likely to cause chronic infections in mice compared to E. coli
with the protein intact.
In the initial days of the infection, both the strains multiplied to
similar levels. However, by the end of the fourth week, the bacteria lacking
the FmlH were found to be 1,000 times less abundant in the bladder and 100
times less abundant in the kidneys than the bacteria with the protein.
"We found that the Fml pilus
plays little to no role in acute bladder infection
, but after the
establishment of infection and the onset of inflammation, it contributes to the persistence of bacteria
in the bladder
," said Conover, who led the study as a researcher in
Vaccination Studies In Mice Using The FmlH
The researchers administered one
group of mice two doses of a vaccine made from a piece of the FmlH protein,
four weeks apart.
Another group of mice received mock vaccinations without
Both groups of mice were infected with E. coli and the amount of
bacteria in their bladders and kidneys, one, two and three days after
infection, were estimated. On day one, there was no difference in the number of
bacteria between the mice that received the vaccine and those that didn't.
However, by the third day, the unvaccinated mice had over 1,000 times more
number of bacteria in their bladders and 100 times more bacteria in their
kidneys than the vaccinated mice.
"This is a proof of concept that
we can interfere with the ability of the bacteria to adhere to the bladder and
reduce chronic bladder infection and spread to other parts of the body,"
said. "We are continuing to work on developing vaccines and drugs that are
effective in blocking the interaction between the bacteria and the body to
prevent the establishment of disease."
About Urinary Tract Infection
Infection of the urinary tract
comprising the kidneys, ureters, bladder and urethra
is referred to as UTI.
It is most commonly due to E. coli, a bacteria that occurs in the bowel.
UTIs are very common and are responsible for nearly 10 million healthcare visits annually
Women are more likely to develop UTIs compared to men, due to their
shorter urethras and proximity of urethral opening to the anal and vaginal
Signs and Symptoms of UTI
Scope Of This Study For
- Feeling an urgency to urinate, passing only a few drops of urine
- Burning feeling during urination
- Pressure, or
pain in the lower part of the abdomen
- Cloudy or blood-stained urine
- Fever with chills
The researchers have showed that
FmlH protein is capable of binding to human bladder cell lines, indicating that
the results in mice may be applicable to humans too
"Taking biopsies of human bladders during a UTI would be contraindicated
because of the risk of spreading the bacteria, so the cell lines are the best
model of human infection we have," Conover said.
further studies show that vaccination could reduce severe disease in models of
human infection, it could well mean new therapeutic options for UTI, made more
significant in the scenario of emerging antibiotic resistance
"Our findings reveal how bacteria have evolved a mechanism to colonize
the bladder in order to persist and cause UTIs, and our vaccination study
suggests that inhibiting this mechanism could be part of a viable approach to
treating or preventing these infections," said Scott Hultgren, PhD, the Helen
L. Stoever Professor of Molecular Microbiology and one of the study's senior
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