The bladder is not
a friendly place for most invading bacteria.
‘A combination vaccine with both siderophores and the carrier protein from the bacteria block E.coli growth in the bladder and kidneys.’
But for those that have figured out
how to scavenge iron from their hosts, it is a suitable
medium to grow and reproduce.
Millions of women suffer
from painful, burning, potentially dangerous urinary tract infections
Developing a Vaccine Against UTI
Women suffering recurrent UTIs are
the most likely candidates for a vaccine, says first author of
the paper and research fellow Laura Mike, Ph.D.
With E. coli
gaining resistance to most
commonly used antibiotics used
to treat UTIs
, or prevent recurring ones, the search for a vaccine takes on new
urgency, says Harry Mobley, Ph.D., senior author of the new paper and chair of
the Department of Microbiology and Immunology at the University of Michigan Medical
The results are published in
of the National Academy of Sciences
by a team from the University
of Michigan Medical School.
Siderophores and Vaccine Made From Uropathogenic E.coli
prevented UTIs in mice by vaccinating them with the same molecules that the
bacteria usually use to grab iron and fuel their growth.
These iron-grabbing molecules are
These molecules bind and transport
iron in microorganisms.
produce "stealth" siderophores that evade the host immune system and
are unique to them. That makes these molecules good
candidates for a vaccine without unintended consequences.
The same team previously reported
success in preventing UTIs using a vaccine made of proteins
from the bacteria, called uropathogenic Escherichia
coli or UPEC.
approach or the siderophore approach alone provided no complete protection, but the two approaches together might.
Using the Vaccine
Combination in Mice
assessed the effect of siderophore vaccination in several ways.
They applied two
different UPEC stealth siderophores inside the noses of mice, several times
over the course of two weeks.
A week later, they applied UPEC
bacteria directly into the mouse bladders, waited two days, and then looked at
their urine, bladder and kidneys, which get involved when a UTI rages out of
Effects of the Vaccine:
When each of the two siderophores
was administered individually, modest protection against UTI resulted.
The mice treated
with both siderophores and the carrier protein at the same time produced a much
"We saw efficacy more in the
kidney than in the bladder, suggesting that this approach may be most useful in
preventing advanced UTIs," says Mike.
"Our next challenge is
creating a combination vaccine that also employs proteins that UPEC bacteria
use to bind their iron-laden siderophores, and test other adjuvants to increase
the response." Mike added.
Urinary Tract Infection
A UTI is an infection in the urinary tract.
Infections are caused by microorganisms including fungi, viruses, and
The most common cause of UTIs is bacteria.
Under normal circumstances, bacteria that gain entry into the urinary
tract are removed by the body.
In patients whose natural defenses are lowered, the bacteria can cause infection.
infection occurs in the urethra, it is called urethritis.
- When infection occurs in the bladder,
it is called cystitis.
- When bacteria infect
the kidneys, it is called pyelonephritis.
Annual expenditure of UTI care in the United States exceeds $3.5
As much as half of the women get
affected at some point. Among the affected ones, chances of re-infection within
one year are higher.
dangerous bacteria make their own unique siderophores, the approach could be
attempted beyond UPEC and Salmonella.
Recently, U-M researchers showed
the role of siderophores in the ability of a "superbug" bacteria
called Klebsiella pneumonia to cause pneumonia and much worse.
"Using proteins that are found
on the surface of bacterial cells as the basis for vaccination may lack
efficacy because of the variability of the exact protein structure," says Mobley.
"But siderophores are the same across most gram negative enteric bacteria
that cause some of the worst infections. This is a step along the journey, but
it's an encouraging one."
The team is planning to expand
their study to see if they can protect against the bloodstream infection, or
bacteremia, that can cause few UTI sufferers to develop sepsis and die.
uptake in bacteria and the battle for iron with the host; a bird's eye
view - (https://www.ncbi.nlm.nih.gov/pubmed/20596754)
- Urinary Tract Infection In Adults -