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Cystitis: How bacteria get into your bladder

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

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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.

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

S.E. Gould About the Author: A biochemist with a love of microbiology, the Lab Rat enjoys exploring, reading about and writing about bacteria. Having finally managed to tear herself away from university, she now works for a small company in Cambridge where she turns data into manageable words and awesome graphs. Follow on Twitter @labratting.

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

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  1. 1. tsurman7 10:20 pm 10/7/2012

    I can see why physicians shy away from telling their patients the detail of this infection.

    Link to this
  2. 2. S.E. Gould in reply to S.E. Gould 5:23 am 10/8/2012

    Thanks for the comment! I actually thought it was pretty cool, in a horrific sort of way. I’d certainly never heard about the latent bacteria before, or how easy it was for them to sneak up the urethra. It’s sort of comforting to know that an attack isn’t just caused by me screwing up with hygiene or hydration.

    Link to this
  3. 3. helenea85 8:51 am 10/8/2012

    We learned about the correlation between cystitis and sexual activity in high school. I never met a woman who didn’know that skipping the bahroom visit after sex is equal to hell.

    Link to this
  4. 4. ironjustice 10:15 am 10/9/2012

    One problem which is becoming more an more understood is the role of increased iron levels in the body and the risk of infection. E.coli has been shown to ‘outperform’ other less pathogenic bacteria such as lactobacillus WHEN the iron levels in the body are higher than normal.
    “Researchers isolate iron as probiotic blocker during active IBD. Certain probiotic strains underperform in the presence of iron-rich environments created during the active phase of inflammatory bowel disease (IBD), UK researchers have found.”

    It has been shown the sugar mannose to have an effect on the rate of UTI’s.
    “An experimental treatment for urinary tract infections has easily passed its first test in animals,alleviating weeks-long infections in mice in as little as six hours.”
    “The compound is a novel derivative of the natural sugar called mannose, making it unlikely to be toxic”

    It has also been shown the bodies own antibiotic , lactoferrin , is effective BUT it has also been shown when iron levels are high , lactoferrin is unable to ‘lock up’ the iron efficiently.
    “When this protein is in the iron-free state, it is capable of a direct bactericidal effect on Streptococcus mutans and Vibrio cholerae.”
    “Here we show that lactoferrin, a ubiquitous and abundant constituent of human external secretions, blocks biofilm development by the opportunistic pathogen
    Pseudomonas aeruginosa”

    Cystitis is sometimes diagnosed when it is actually a problem with the pudendal nerve. Very , very painful.

    Link to this
  5. 5. ironjustice 10:58 am 10/9/2012

    One of the problems of birth control is many times a woman will lose her menses.
    “No period yet while taking yaz birth control pills”

    Menses are known to keep the iron levels lower. When the iron levels rise infection is able to access the iron.

    Link to this
  6. 6. Mimi Rivkin 7:55 pm 10/9/2012

    I appreciate the article and will keep ‘bicarbonate of soda’ in mind. I’m sorry you knocked cranberry- because after years of UTIs I was put on daily Cephalexin. Changed Urologists after a few months who said ‘ stop the antibiotics and take cranberry.’ I did and remained free for 2 years- had one infection cleared with Cephalexin and went back on Cranberry for another 2 years. Recently I had several infections, and after Cipro seemed to stop them, they came back. So I went to cranberry concentrate (in juice) instead of capsules- and I’m clear for the first time in a year. Oddly, my son inlaw now takes the capsules with good results too. Maybe the research doesn’t provide enough evidence, but my Urologist prescribes it. It may not help everyone but it certainly has saved me from a (shorter) life of killer antibiotics. Thanks, Mimi

    Link to this
  7. 7. tsurman7 10:58 pm 10/9/2012

    For the author,

    Yes, they are sneaky! I have probably taken too many classes on bacteria for comfort, learning that one day current antibiotics will be as useful as a B.B. Gun vs. a battle ship. What I can say is that there are definitely practices that can be done by men and women to prevent the infections.

    Link to this
  8. 8. Jbyrne 12:52 am 10/10/2012

    Hey Rat!
    Nice piece :)
    I wrote about this a little while ago and found some evidence for cranberry activity. Be interested to know whether you saw those refs.

    Link to this
  9. 9. S.E. Gould in reply to S.E. Gould 7:53 am 10/10/2012

    For some reason my comment notification isn’t working, so wasn’t expecting all these!

    @helenea85: I didn’t get any sexual health classes at my school, so that particular nugget of important information passed me by. And given the natural body reaction after high periods of intense activity late at night is mostly to fall asleep it wasn’t something that seemed obvious to do!

    @Ironjustice: interesting info, but not all birth control pills stop periods. Mine don’t unless I purposefully over-run them. I don’t know of any studies looking into the correlation between stopping periods and a change in cystitis but would be intriguing if there were.

    @Mimi: I know cranberry does help, and there are some nice articles showing effects preventing long-term cystitis. What they don’t do is prevent immediate symptoms. I do have a slight vendetta against cranberry advice, if only because it is often proposed like some kind of miracle cure with no real instruction as to how and when to take, appropriate dose etc. I certainly wasn’t aware until I started researching that cranberries were more for prevention than immediate relief. Most of the cystitis advice tends to be vague and old-wives-tale-ish, which gets annoying after a while.

    @tsurman7: There are practices that can help with infection control, but completely ‘preventing’ them places a large burden on the patient to maintain a change of lifestyle. Cystitis in men is far less common, and often due to major internal problems; certainly I would advise any men with cystitis to get to a hospital asap.

    @Jbyrne: ditto on the cranberry :p I remember that post!

    Link to this
  10. 10. ironjustice 12:23 pm 10/10/2012

    Cranberries were found to be binding up of the aforementioned iron.
    “Iron-binding properties of plant phenolics and cranberry’s bio-effects”
    “Strong iron-binding properties have been confirmed for the compounds containing the “iron-binding motifs” identified in their structures.”

    Reduces the bacteria’s ability to access the iron and thus allowing for it to be eliminated , JUST like the bodies own lactoferrin does.
    “Lactoferrin, an iron-binding glycoprotein synthesized by neutrophils and exocrine glands, plays an important role in human innate defense mechanisms against bacteria, fungi, and viruses. First, a bacteriostatic activity of lactoferrin, depending on iron withholding to bacteria, and successively a bactericidal iron-independent effect, related to its binding on bacterial
    surfaces, was recognized.”

    Which is why they have been using iron binding antibiotics like ciprofloxacin.
    “Ciprofloxacin: a novel therapeutic agent for iron overload?”
    “Decrease in the liver and heart iron following the
    “Ciprofloxacin, a fluoroquinolone antibiotic that is highly toxic to human tissue yet still prescribed like candy by doctors.”
    “Overnight the sales of cipro skyrocketed. Millions of dollars in profits were generated by the drug companies”

    Link to this
  11. 11. moricerianna 11:32 pm 11/9/2014

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    Link to this

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