Urinary tract infection is usually seen as a one-off acute infection resolved through antibiotic or self-management treatments. More on acute UTIs.
But many people continue to have UTI symptoms after their initial treatment ends or find their symptoms soon return. This is a recurrent UTI.
A recurrent UTI is clinically defined as three episodes of a UTI occurring within a 12 month period or two episodes within the previous six months.
Standard thinking is that recurrent UTIs happen because
- of a persistent infection – that hasn’t gone away despite treatment
- of reinfection by new bacteria.
Persistent infections are defined as a bacteria that was the cause for the original UTI not being completely cleared from the bladder by initial treatment. The infection can remain detectable in the urine, and even after further treatment continues to cause symptoms. The sufferer is caught in an ongoing cycle of symptoms and treatment.
Persistent infection is also chronic urinary tract infection or chronic cystitis.
Reinfection is defined as the original infection clearing with treatment but then the same or a different bacteria causes a new infection.
New research now shows that the reinfection is unlikely to be the cause of long term UTI symptoms but indicates chronic cystitis or a chronic UTI.
So, what is going on in the bladder whilst a sufferer struggles on?
The first thing the body does, as part of the immune system response, when it senses an upsurge in potentially harmful bacteria or pathogens in the urinary tract is to shed bladder wall surface cells (known as epithelial or urothelial cells). It sweeps them away to prevent penetration of the outer lining of the bladder wall (the urothelium) by bacteria. These epithelial cells are excreted out of the body when you urinate.
The urothelium cells have receptors that detect certain molecules on pathogens and mounts an immune response that includes the release of specific chemicals known as cytokines that try to eliminate pathogens. This process causes inflammation of the bladder lining and increased nerve sensitisation – which account for the pain signals that we feel as part of a UTI.
As a result of this inflammatory response, another key immune system response – white blood cells – infiltrate the urothelium. The white blood cells are attracted by the cytokines which are released by the infected cells.
These white blood cells are responsible for the specific recognition of pathogens and their removal. They secrete antibodies, which are proteins that bind to foreign microorganisms and mediate their destruction.
Unfortunately, some bacteria can suppress these chemical responses by the infected cells and are able to down-regulate a gene that plays a role in the production of these chemicals by the immune system.
Intracellular infection
Bacteria such as E. coli (the most common bacteria causing UTI) have two methods to evade this initial immune system response. Bacteria can:
- Anchor themselves to the bladder wall, with finger like roots called lectins, and start to invade the cells of the bladder wall, urothelium, become embedded and start to replicate.
Read more on Scientific American. - Change shape so that they can more easily penetrate the bladder urothelium lining. This penetration and subsequent replication (colonisation) is known as an intracellular infection.
Read more on PLOS.
Once inside the bladder lining, bacterial cells grow at different speeds and depths. This causes confused signalling by the immune system as infected cells signal their distress but the white blood cells can’t reach these cells often deep within the bladder wall.
This leads to detectable white blood cells in the urine and causes the ongoing painful inflammation.
If an infection isn’t cleared by either the immune system or antibiotic or antimicrobial treatments prolonged inflammation of the urothelium can cause the thickening of the bladder and urethral walls – which can cause symptoms such as reduced urine capacity, voiding and obstruction.
Chronic UTIs are usually polymicrobial – caused by several different types of bacteria. The bacteria identified in your UTI may well be different to someone else. It also explains why different people experience different symptoms.
One research analysis notes “A single dormant microbe, woken from slumber, can become 1 million microbes before sundown”.
These dormant bacteria are known as persister cells. This process of cellular bacterial persistence can predispose people to recurrent UTIs even after antibiotic or antimicrobial treatment or sudden emergence of symptoms after a long period of good health. Read more on ASM.
Biofilms
Once a critical mass of bacteria have penetrated the bladder lining and formed a colony they begin to produce a biofilm around or inside the cells as a protective measure. Read more on PubMed Central.
Biofilms are not new to nature, they are quite common – slippery river and stream bed rocks are an example of a biofilm in nature. They are also found all over the body – such as plaque on teeth.
Biofilms provide a protective layer made of polymers – substances composed of molecules with repeating structural units that are connected by chemical bonds. The different bacterial species within these biofilms are able to communicate with each other and as each has different resistances, they can teach each other to become more and more resistant to antibiotics.
According to the National Institutes of Health (NIH) around 65% of all microbial infections, and 80% of all chronic infections are associated with biofilms. Read more in the Journal of Microbiology and Infection.
The body is made up of many complex biofilms and a key point to remember is that not all of them are bad for you. Try to eradicate biofilms from the body and you could become very ill indeed.
Current testing misses these types of infection
Intracellular infections and biofilms make it extremely difficult for standard testing methods to initially detect an infection given because bacteria are embedded into the wall of the bladder.
During a ‘flare’ of symptoms, bacteria may be released from within the bladder lining into the urine. But current laboratory analysis for UTI infections look for a fast growing, single causal bacteria rather than several bacteria some of which may take longer to culture in the laboratory or die on exposure to oxygen. So results can be reported as negative, low growth or mixed growth and the sample is discounted for infection.
If a bacterial strain is found it’s extremely hard for some antibiotic treatment to penetrate the biofilm and eradicate a multi bacterial infection. The negative charge of biofilms restricts entry of some antibiotics, while other antibiotics are neutralized by specific biofilm bacterial enzymes.
Antibiotics can reduce or eradicate one type of bacteria but they may cause another undetected type to multiply and/or not reach an embedded infection because the bacteria are still dormant within the cells.
Read more about how a UTI becomes a chronic infection in our explainer.