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Lab Rat

Lab Rat

Exploring the life and times of bacteria

Cystitis: How bacteria get into your bladder

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Over the last year, it's become more and more apparent that I do, in fact, have recurrent cystitis. Having cystitis is a bit like entering the matrix - until I had my first attack I'd never even known it was a disease. It doesn't appear in books, films or classroom lessons (particularly given that my school didn't give any lessons related to sexual health) and nobody had even suggested it as an illness possibility. And then I had an episode and found out that not only do most women have it at least once in their lives, getting it around three times a year is apparently perfectly normal. Suddenly there was this new and unexpected level to the world.

For those who have not yet entered the matrix, cystitis is a bacterial urinary tract or bladder infection. The main symptoms are a strong and desperate desire to pee coupled with pee that feels like burning acid, which is not a happy combination. If left for too long, eventually you start to pee blood which is completely terrifying the first time it happens. It tends to occur when bacteria from the outside world make their way into the urethra (the little pipe where pee comes out) and given that women have far shorter urethras than men, it can happen to them fairly frequently. Nobody is quite sure what leads to an attack, or why some people get it far more often than others, but anecdotal evidence suggests a strong correlation with sexual activity, personal hygiene, and/or dehydration.

This is your bladder on cystitis. The purple dots are the white blood cells that cause inflammation. Image credit below.

There isn't a huge amount of research on cystitis, which is why going to the doctor tends to result in not much more than vague murmurings about cranberries, loose underwear and drinking plenty of water. (As an aside, it wasn't until my third attack that I was given the only piece of really useful anti-cystitis advice I've ever received: pee after sex). So I'm always interested in new papers that come out discussing it. In particular there's a really interesting paper in PLoS Pathogens at the moment (reference below) detailing the life cycle of the bacteria that cause cystitis.

The most common bacterial cause of cystitis is E. coli, because there tends to be quite a lot of it hanging around on the body. Because of this, the body usually has quite an efficient innate immune response that keeps the bacteria from getting anywhere near the tissues or bloodstream, but for some reason in cystitis this response simple isn't effective. This may be genetic factors in some women, for others there are clear physical reasons (such as a strangely formed urinary tract, or a problem with the kidneys) and is definitely helped by the fact that the bladder is a sort of water reservoir, where bacteria can settle down and flourish.

Bacterial colonies on the surface of a hot spring. Generally bacteria like bodies of warm water. Credit link below.

The first challenge the bacteria face is getting up the urinary tract in the first place. True, it's fairly short in women, but it's still a piece of human tissue protected with white-blood cells and with a regular streams of water running through it. Pathogenic bacteria have a wide range of adhesive molecules and other binding agents, which, when they bind to a surface, cause the bacterium to change from a floating blob to a blob capable of crawling along a surface. The particular E. coli associated with cystitis has a whole host of other molecules to help with binding to urinary tract tissue, although it is not yet clear which are directly associated with the infection in humans (research has been done mainly on mice). The E. coli is also able to bind and sense urine, and uses the rush of urine flow as a signal to cling tightly to the tissue where it's attached.

Once they get into the bladder, the E. coli are then internalised by the host-cells in order to destroy them. While most of the bacteria will be killed in this way, others actually start to form little biofilm-like clusters inside the cells. This highly organised little bacterial city is surrounded by a sticky mess of proteins and sugars, which protect it from the cell trying to kill it.

Remains of a Staphylococcus infection from a catheter. The stringy gooey bits between the spherical bacteria are the remains of the biofilm that would have surrounded the entire colony. Image credit below

This is where the story starts turning into horror sci-fi. Remember this is all happening inside a human bladder.

The biofilm starts to take over the cell it's growing in, engulfing the nucleus and filling the cytoplasm. It gets so large that the cell actually starts to bulge inwards, into the bladder space. This large bulging cell then starts to extrude bacterial filaments that grow outwards from the surface, latch onto surrounding cells, and start infecting them as well. Not only are the bacteria starting to take over the cells in the bladder, they also suppress the answering human immune system by suppressing the production of cytokines (small immune system signalling molecules) and encouraging the production of IDO, a molecule which tells the immune system that enough cytokines have been produced and they don't need to make any more. By breaking down communication channels within the immune system, the bacteria can evade attack.

The problem with the outer tissue layer of the bladder though, is that it's continually being shed through exfoiliation, which makes it a rather unsafe place to have a bacterial colony. For longer lasting survival, the bacteria can burrow down to the underlying basal epithelium and surround themselves with a protective network of actin molecules. These bacteria are resistant to antibiotic attack, and can simply lie dormant for several months. The mechanisms by which it stays like this, or by which it initiates recurrent cystitis, are still a mystery.

One of the main problems with recurrent cystitis, from the point of view of the sufferer, is that each bout of infection leaves the tissues inflamed and, even after healing, more likely to succumb to an infection again. Like asthma, diabetes, and various other long-term diseases and symptoms, it's not something that can be cured, it's something that has to be lived with.

If you do suffer from cystitis, the internet contains many sources of advice, all of which tend to list the same sort of things. The methods I've found most work for me are: peeing after sex, drinking 4/5 pints of water a day and taking bicarbonate of soda if I start to feel twinges. Despite what they tell you, there is no real evidence for the cranberries.

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Credit for image 1

Credit link for image 2

Credit link for image 3

Reference: Jorgensen I, Seed PC (2012) How to Make It in the Urinary Tract: A Tutorial by Escherichia coli. PLoS Pathog 8(10): e1002907. doi:10.1371/journal.ppat.1002907

The views expressed are those of the author and are not necessarily those of Scientific American.

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