Biofilms and their role in recurrent UTIs

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Spencer is a Co-Founder of Uqora. Trained in biochemistry at UC Berkeley, Spencer uses his background to provide education on topics including UTIs, urinary tract health, and non-antibiotic UTI treatments.

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A recurring urinary tract infection can be defined as at least 3 episodes of UTI in the previous 12 months or at least 2 episodes within the previous 6 months. While these UTIs seem to happen independently of one another, they are often caused by bacteria from an initial infection that were never cleared. Bacteria are able to survive antibiotic treatment and the immune system by staying protected by biofilm. These bacteria eventually end their dormancy, grow their populations, and cause what is called a relapse infection or recurring UTI (rUTI). Another round of antibiotic treatment again kills the vast majority of the infecting bacteria, but some may again remain, protected by biofilm. This cycle can lead to frequent and recurring urinary tract infections.

An estimated 25% of women who experience a UTI will go on to battle recurrent infections (1). These infections can be frequent and difficult to fight. They account for the majority of UTIs. In fact, DNA sequencing confirms that ~77% of all UTIs are relapse infections caused by the exact bacteria that survived antibiotic treatment after an initial infection (2). Biofilm is critical to understanding recurring UTIs. For our 3 key things to know about rUTI, go here. 

E. coli and other types of bacteria that infect the urinary tract make biofilm, a shield that protects communities of bacteria. Often referred to as “cities” of bacteria, these biofilm communities can lay dormant and eventually cause relapse infections. Bacteria in the urine typically start an infection by attaching to the wall of the urinary tract, which provides a surface. Once attached to this surface, bacteria may produce biofilms.

Biofilms are sticky networks composed of carbohydrates, proteins, fats, and DNA. These networks allow bacteria to stick to each other in groups and stick to the urinary tract wall, ultimately protecting them from the surrounding environment. Bacteria that are unable to produce biofilm are much less likely to cause rUTI. Conversely, bacteria with higher biofilm-forming capacity are much more likely to cause rUTI (2).

Why is rUTI caused by biofilm-forming bacteria so difficult to treat? The biofilms insulate bacteria from the immune system and from antibiotics. Immune cells like white blood cells work by identifying, engulfing, and destroying bacteria. While within biofilm communities, bacteria are insulated from the white blood cells (1).

Biofilms also act as a barrier to antibiotics. Unable to penetrate the barrier, the antibiotics cannot kill the bacteria within. Potentially even more troublesome, bacteria in biofilms may be more likely to develop antibiotic resistance to any antibiotics that do make it through the barrier. Bacteria are able to pass the genes that confer resistance back and forth, and their close association in the biofilm-protected communities increases this likelihood (3). Finally, Bacteria within biofilms may be replicating or may be dormant. Many antibiotics work by killing the bacteria during replication. If the bacteria are dormant, the antibiotics will not take effect.

Unfortunately, recurring UTIs can get even more complicated. Biofilms are a key mechanism by which bacteria can evade us, and perhaps the most common, but there are others. Bacteria can also invade the tissue of the bladder and form what are called quiescent intracellular reservoirs (QIRs) which can lay dormant within the cells of the tissue and serve as populations from which new infections can emerge. Cells on the surface of the urinary tract are cyclically turned over. Those on the surface die off and are excreted. When this happens, these QIRs are released and can create new infections (1).

QIRs inside of cells can cause an immune response and UTI symptoms, but since they are inside the cells they can be difficult for immune cells to find. Plus, there may not be any bacteria in the urine, so urine cultures may come up negative. This is a possible explanation for interstitial cystitis (IC), which is characterized by recurring UTI symptoms but repeat negative cultures. You can learn more about how a recurring UTI is a possible explanation for interstitial cystitis here.

Biofilms are not unique to the urinary tract. According to the NIH, biofilm-forming bacteria are involved in up to 80% of all infections, with urology being one of the main fields in which biofilm can become a serious problem (4). For instance, dental plaque, created by bacteria in the mouth, is a biofilm. Biofilms can also form during vaginal infections like bacterial vaginosis (BV), which can lead to difficult to treat recurring BV episodes (5).

Unfortunately, current antibiotic treatments do not effectively address biofilms. More research and more development is needed to create ones that do. Biofilms and QIRs are more likely to form when 1) bacterial populations are higher and 2) an infection is allowed to progress. This provides more opportunity for bacteria to create populations encased in biofilm and to invade the surrounding tissue. It may reduce the likelihood of rUTI to develop if acute UTIs are treated quickly and not allowed to progress.

1. Glover M, Moreira CG, Sperandio V, Zimmern P. Recurrent urinary tract infections in healthy and nonpregnant women. Urol Sci. 2014;25(1):1-8. doi:10.1016/j.urols.2013.11.007
2. Ejrnæs K. Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli. Dan Med Bull. 2011 Apr;58(4):B4187. PMID: 21466767.
3. Delcaru C, Alexandru I, Podgoreanu P, et al. Microbial Biofilms in Urinary Tract Infections and Prostatitis: Etiology, Pathogenicity, and Combating strategies. Pathogens. 2016;5(4):65. Published 2016 Nov 30. doi:10.3390/pathogens5040065
4. Sara M. Soto, "Importance of Biofilms in Urinary Tract Infections: New Therapeutic Approaches", Advances in Biology, vol. 2014, Article ID 543974, 13 pages, 2014. https://doi.org/10.1155/2014/543974
5. Machado D, Castro J, Palmeira-de-Oliveira A, Martinez-de-Oliveira J, Cerca N. Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions. Front Microbiol. 2016;6:1528. Published 2016 Jan 20. doi:10.3389/fmicb.2015.01528