- Urinary tract infections(UTIs) affect millions of women worldwide annually.
- Researchers have prevented UTIs in mice by vaccinating them with iron-grabbing molecules called siderophores.
- They also used another vaccine made of proteins from the bacteria, called Uropathogenic Escherichia coli or UPEC.
- When the mice were treated with both siderophores and the carrier protein together, it offered greater protection against UTI..
The most common
UTI-causing bacteria could be tackled by turning their own iron-scavenging power
The bladder is not a friendly place for most invading bacteria.
But for those that have figured out how to scavenge iron from their hosts, it is a suitable medium to grow and reproduce.
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 School (Ŭ-M).
The results are published in the Proceedings of the National Academy of Sciences by a team from the University of Michigan Medical School.
Siderophores and Vaccine Made From Uropathogenic E.coli
Researchers have 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 called siderophores. These molecules bind and transport iron in microorganisms.
The bacteria 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.
The protein approach or the siderophore approach alone provided no complete protection, but the two approaches together might.
Using the Vaccine Combination in Mice
The researchers 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 control.
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 greater effect.
"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 bacteria.
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.
- When 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.
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.
Since other 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.
- Siderophore 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 - (https://www.niddk.nih.gov/health-information/health-topics/urologic-disease/urinary-tract-infections-in-adults/Pages/facts.aspx)