Non-antibiotic Therapies for Cystitis Treatment

A recent study provided new insight into the development of cystitis, and may lead to new developments of antibiotic therapies to treat the later stages of the bladder infection.

Published in Cell Host & Microbe, the study’s findings revealed that the bacterium Escherichia coli (E. coli), the main bacterial cause behind cystitis, uses 2 complementary types of pili to adhere to bladder cells, depending on the infections stage.

It is well-documented that in the beginning stages of cystitis, a specific type of pili called type 1 pili (fim) is used to bind to the surface proteins of bladder cells. This process fuels inflammation that results in tissue damage and painful symptoms.

Although E. coli can carry additional pilus types, the actual function of many of these is unknown; however, in the current study researchers were able to shed new light on the matter. For the study, researchers set out to examine the workings of F9 or fim-like (fml) pilus, another E coli pilus type, and to identify the binding sugars used by F9 pili to adhere to bladder cells.

Researchers found the receptors were present on the bladder surface only during later stages of the infection, when the inflammation and tissue damage caused the bladder cells to change their sugar coatings. When the pili were not present, however, the E. coli had a 1000-fold disadvantage of holding on in the bladder during late stage infections.

“E. coli is a very versatile bacterium, with up to 40 types of pili across the different disease causing strains,” said researcher Ségolène Ruer. “The pili direct the bacteria to their specific site in the body or to a particular host such as humans or farm animals, where the bacteria cause a variety of gastrointestinal and urinary infections. The observation that the bacterium’s F9 pili only come into the picture after infection-induced changes in the bladder tissue was unexpected, and possibly the reason why its role in urinary tract infections remain unknown for such a long time.”

The findings indicated that the bacteria appeared to have a complementary pair of pili that were utilized for bladder interaction during early and late stages of infection, allowing the bacterium to anticipate infection-induced changes in the bladder tissue.

“With multidrug-resistance of uropathogenic E. coli being on the rise, new therapeutic compounds are currently in development,” said researcher Scott Hultgren. “We have previously shown that non-antibiotic compounds can be used to block type 1 pilus function and that this has an empowering effect during antibiotic treatment of urinary tract infections. The type 1 pilus adhesion also forms the basis of a vaccine that is entering clinical trials.”

The findings provide a road for the potential development of non-antibiotic therapies, according to the study.

“Targeting F9 pili showed to suppress the further development of urinary infections in mice,” said researcher Han Remaut. “The use of F9 pilus inhibitor molecules may be particularly interesting during advanced urinary tract infections, when patients report to the clinic with symptoms; and in patients that suffer from recurrent and chronic infections. A critical next step would be to get urinary tract tissues from patients and find out if we can draw a parallel between the observations we made in mouse models and bladder infection in humans. The purpose? To find new inhibitor molecules that could be used as therapies when antibiotics are no longer efficient.”