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In this series we will ‘interview’ a range of micro-organisms to try to get a better understanding of what makes them tick.
“Know your enemy and know yourself and you can fight a hundred battles without disaster” Sun Tzu [ 1 ]
… so it is our most common enemy.
Escherichia : it’s my Genus or ‘tribe’ name. We are bacteria from the family Enterobacteriaceae, which means we mostly live in the large intestine of animals and humans. However, we are pretty adaptable, and have found lots of other places to live too. ‘coli’ is my species name, often followed by letters and numbers denoting my ‘strain’. You used to identify us by our growth and susceptibility patterns. These days your scientists can use our DNA to be much more specific.
I’m a bacterium, a single celled life form descended from some of the earliest forms of life on the planet. Some have evolved to live in or on you, our ‘hosts’ in relationships that are symbiotic (peaceful cooperation ) and some, like us E.coli, are parasitic, where we take from you to live.
That is why you call us ‘pathogens’ and yes, we are responsible for many illnesses in our hosts.
We E.coli are ‘rods’ … short rod-shaped cells. Other bacteria have many other shapes or ‘morphologies’ e.g. spheres ( cocci ), strips of spheres ( streptococci ), strips of rods ( streptobacilli ), some are even corkscrews, spirals, filaments : SO many forms ! [ 6 ]
I’m about 2 µm ( micrometers ) long and 0.5 to 1 µm across. A micrometer is 1/1000th of a millimeter.
So, put about 500 of us end-to end and we’d span 1mm.
We are about 1/10 the size of most of your cells. Too small to see with the naked eye, but easy enough to see with a microscope of 200 x or more magnification.
There are 2 main types
The grappling hooks are very significant, especially in UTI’s.
The ‘hooks’ are Lectin molecules on the end of our pili, and they grab hold of Mannose molecules which are on the surface of human cells. These Mannose ‘receptors’ are actually a part of your blood-type system.
Having D-mannose floating around in your urine means that our grappling hooks grab hold of this, instead of attaching to the cells of the lining of the bladder. So, because we are not attached, and we are freely flushed away when the bladder empties. [ 7 ] [ 8 ] [ 9 ]
That’s how Waterfall D-Mannose works. [ 10 ]
Oh, we have been around for a VERY long time. Our ancestors were among some of the first forms of life to appear on the planet, at least 4 billion years ago. We are extremely adaptable and we have evolved to live in almost every habitat on earth.
"You can find microbes everywhere—they're extremely adaptable to conditions, and survive wherever they are." [ 11 ]
When you humans came along you proved to be great hosts, and we moved in straight away !
We E.coli specifically like to live inside warm blooded animals, usually in the large intestine. Which means we are present in large numbers in faecal matter. We can manage to survive quite well outside the body, but we like to find our way back in to really thrive.
So, contamination with faecal matter is a possible way of getting transmitted.
Back in 1894 a Danish scientist called Hans Christian Gram was working on ways to make bacteria more visible under a microscope. [ 12 ] He discovered that his stain, made up of crystal violet and safranin made some bacteria turn purple ( Gram positive ) and some turn red ( Gram negative ). [ 13 ]. At the time, Gram had little idea how significant this was.
Later work by many scientists has demonstrated that this reflects a significant difference in the way the 2 groups of bacteria are structured, and how they function. [ 14 ]
Gram +ve (gram positive) bacteria have a single cell wall made of peptoglycan ( gram stain can get through this and turn the inner parts purple )
Gram -ve (gram negitive) bacteria have a double cell wall, a thin layer of peptoglycan, and outside it a lipid layer. ( gram stain can’t get through this )
This outer lipid layer is very significant : think of it like a ‘slime layer’ …
You are both where we live and what we eat.
We are parasites, pathogens.
We get our energy from organic compounds which we get from you. The scientific terms is ‘chemoheterotrophs’ [ 15 ]
Your bodies are a great source of everything we need, including organic carbon and nitrate for our energy, as well as trace elements such as Potassium, Magnesium, Iron, Calcium. [ 16 ] Where this is not available floating around us in the urine, we also break open your cells to release the goodies inside.
We absorb these small molecules directly through our cell membranes, sometimes by diffusion, whilst some others have specific ‘portals’.
No, although I can. I prefer to live in an anaerobic (oxygen-free) environment, … although I can survive in the presence of oxygen.
For this reason they call us ‘facultatively anaerobic’.
My metabolism is adapted to function this way, using organic carbon and nitrate to produce energy the way you use oxygen. Both of these I source from you.
As soon as we grow to a certain size, we split our bodies and become two. This is called ‘binary fission’. It is asexual, and we can do it incredibly quickly ; if food and nutrients are plentiful ( we are acid loving)this can happen in as little as 20 minutes ! ( we call this our ‘generation’ or ‘doubling time’ ).
Thus our numbers increase exponentially : 1 becomes 2, 2 becomes 4, 4 becomes 8, 16, 32,64 … and on. Here’s a great video showing what that looks like : https://youtu.be/KIpcCyuypzg
This power to multiply quickly is one of our greatest strengths.
Warmth, moisture, food, protection from attack : a nice host to infect, and we’ll do our favourite thing … multiply !
Hygiene : it hampers our spread to new hosts.
You. For the most part we don’t want to actually kill you, though this happens sometimes.
We just want you to go on being our hosts.
Really, we exist only to survive and reproduce.
I’m a parasite, a pathogen. I live in you and feed on you.
The urinary tract is a fairly hostile place to live,
But it has some advantages too,
Your bladder and urinary tracts have a handy feature ; they open to the outside via the Urethra.
That’s our way in. And out.
In women it’s a shorter journey to the bladder, one reason why bladder infections are more common in women.
Guys, don’t be complacent, we can get into you too ! In men we can also invade the prostate.
Since we are talking faecal matter, good public and personal hygiene are your best line of defence and are the best way to prevent me from getting in. That means HOT, SOAPY water and prolonged hand washing. I really shouldn’t be telling you this.
But no worries, we have many allies and here are some:
Other foods that can be infected with E. coli include:
The great news for us is that whilst we are within your bodies, almost everything that kills us HARMS YOU TOO, including antibiotics. Even killing some of us is not the end of the story: we leave behind debris and toxins which can still do you harm until cleared. And we are cooperative. We work together to allow some to survive.
Outside the body we are much more susceptible; heat, soap & water, bleach on hard surfaces.
Although we can be killed, it only takes a few of us to survive, and as soon as we can, we will multiply again.
Living in the urinary tract is one way : it’s not ‘inside’ the body, and here we are not subject to the same kinds of attack your immune system uses internally.
Where we are attacked, our outer lipid layer is very significant, forming a protective coat and helping shield us from antibodies and white cells.
We have also developed some good hiding strategies, in biofilms and even hiding within your own cells.
We even have a clever way of ‘passing notes’ sideways to each other ( bits of DNA transferred via conjugation ). We have been known to use this to ‘learn’ how to resist things like antibiotics.
However, our main strength is in sheer numbers. We can afford to take heavy losses : there will always be a few survivors.
We E.coli have developed some very clever adaptations to help us live in this harsh environment,
So, you call us “uropathogenic” … pathogens of the urinary tract.
Take me on in battle, and you will find I’m far trickier than you ever imagined !
Once I am inside, your best strategy is to get me out again without a fight - use Waterfall D-Mannose.
We use some of those hairs ( ‘pili’ ) on our bodies as grappling hooks’ to attach to anchor points on the surface of the cells lining the bladder ( epithelial cells ).
The anchor points are molecules of Mannose which are on the surface of human cells. These Mannose ‘receptors’ are actually a part of your blood-type system.
The ‘hooks’ on the end of our pili are Lectin molecules, which grab hold of the Mannose molecules on the epithelial cells. In fact, the more the grappling lines are pulled, the harder the hooks hold on ! You call this a ‘catch-bond’ [ 19 ]
‘Anchoring’ in this way triggers release of my bacterial enzymes which attack your epithelial cells, releasing nutrients for me to eat. This is how I feed on you, and start to do damage. [ 20 ]
If there is D-mannose floating around free in your urine, our grappling hooks grab this, instead of the mannose on the epithelial cells. So, we are not attached, and we are get flushed away in the urine when the bladder empties. [ 7 ] [ 8 ] [ 9 ]
That’s how Waterfall D-Mannose works. [ r10 ]
Yes, your classical immune system is certainly at work in the urinary tract. Compliment, which activates an immune response, white blood cells, and antibodies, can all be found in urine. [ 21 ] But they can’t get to me here in the bladder in quite the same way as they can in the blood stream or within the body.
You humans do have one neat trick, though : Tamm Horsfall Protein ( THP, also known as uromodulin ) is made in your kidneys and flows down with the urine. It has been shown to be a defence factor against E.coli [ 22 ] and other uropathogenic bacteria [ 23 ]. This glyco-protein is positively bristling with receptors, including mannose, which play a role in binding to bacteria and flushing them out.
So you see, Waterfall D-Mannose is acting in exactly the same way your body does naturally : by using it you are just supplementing your natural defences.
Vaccines programme your immune systems to respond quickly when it encounters an ‘invader’.
It puts antibodies into your blood stream, and primes white blood cells to be on the lookout, ready to respond.
There are some things that get in the way of this working very effectively in the bladder and urinary tract ( see my answer to “ Can our immune system fight you ?” ).
However, your scientists can certainly manufacture antibodies against me. Because my outer lipid layer protects much of my surface from things like antibodies, the obvious target is my attachment pili, and the ‘grappling hooks’, which are made of Lectin ( specifically ‘FimH adhesin’ ).
Much work has and is going on in this area, but we E.coli have some surprising tricks up our sleeves.
Although we reproduce asexually, we have some genetic tricks which mean that not every one of our offspring is absolutely identical : there are some variations. Some of these variants may be more susceptible, and some better will be able to survive attack by antibiotics. This is how we have survived for billions of years, by being highly adaptable.
So it becomes all about the numbers. There are billions upon billions of us. Your chemicals might be pretty effective at first, killing almost all of us. But just a few of those variants survive. Now they have the place to themselves, and get busy multiplying. 1 becomes 2, 2 – 4, 4 – 8, and we have quickly grown up a new population, all resistant, all untroubled by the antibiotic.
You are ‘selecting’ the antibiotic resistant ones amongst us, and removing those who are susceptible. It’s pure survival of the fittest : your Mr Darwin knew how it works.
The more you use antibiotics against us, the more often this is happening, and what you end up with is a LOT of us around who are resistant to your nasty chemicals.
What do you do ? - you just keep using them more and more ! You flood the place with them. You try a different antibiotic, and those who survive that one now have resistance 2 ! Then 3 …
… and you only have a handful in your armoury.
Ah, silly humans.
This is one of our new generation, who have acquired resistance to most, if not all of your arsenal of antibiotics. Hence the term ‘multi-resistant’.
They have free reign : it’s just like the days before you discovered antibiotics at all.
Your World Health Organisation recently drew up a list of the world’s most threatening superbugs : we E.coli are in the top ranked ‘critical’ category. [ 26 ]
To win this war you will have to develop new strategies.
We secrete lipids around us ( lipo-polysaccharides and lipo-proteins ). We can also produce other substances, glyco-proteins and polysaccharides ( very like your own ‘mucus’ ). Get enough of us together and this all joins up to form a gooey layer around us, which protects us from outside attack.
Our host’s natural defences, white cells, antibodies, compliment, and even chemicals like antibiotics, find it hard to get through this sticky, protective layer.
A biofilm can be a ’refuge’ for us, from which we can re-emerge when conditions are less hostile.
We don’t always do this ; we can sometimes ‘turn up’ the amount of these substances we secrete, perhaps as a defensive or survival mechanism. Exactly how, and why we do it is something your scientists are still investigating. [ 27 ] [ 18 ]
Cóilín Nunan, a scientific adviser to Save Our Antibiotics
“E coli is now killing more than twice as many people as MRSA and Clostridium difficile combined, so the price of any further inaction will be measured in human lives.’
We are doing very well, thank you.
E.coli, thank you for answering our questions.
Here’s some D-Mannose to hold on to, now please leave.
Toilet flushes. Reader, wash your hands.
[ 3 ] Kahlmeter, G., An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project. J Antimicrob Chemother, 2003. 51(1): p. 69-76.
[ 4 ] Ronald, A., The etiology of urinary tract infection: traditional and emerging pathogens. Dis Mon, 2003. 49(2): p. 71-82.
[ 5 ] Uropathogenic Escherichia coli: The Pre-Eminent Urinary Tract Infection Pathogen pp. 1-66. Nova Publishers : Authors: (David W. Hilbert, Women’s Health Research Center, Medical Diagnostic Laboratories, Hamilton, New Jersey, USA
[ 7 ] Aromatic alpha-glycosides of mannose are powerful inhibitors of the adherence of type 1 fimbriated Escherichia coli to yeast and intestinal epithelial cells. N Firon, S Ashkenazi, D Mirelman, I Ofek, and N Sharon American Society for MicrobiologyInfection and Immunity
[ 8 ] Adherence of Escherichia coli to human mucosal cells mediated by mannose receptors. Nature. 1977 Feb 17;265(5595):623-5. Ofek I, Mirelman D, Sharon N.
[ 9 ] Mannose inhibition of Escherichia coli adherence to urinary bladder epithelium: comparison with yeast agglutination. Urol Res. 1985;13(2):79-84. Ruggieri MR, Hanno PM, Levin RM.
[ 10 ] D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014 Feb;32(1):79-84. doi: 10.1007/s00345-013-1091-6. Epub 2013 Apr 30. Kranjčec B1, Papeš D, Altarac S.
[ 13 ] Brock, T.D. (1999). Milestones in Microbiology 1546–1940 (2 ed.). ASM Press. pp. 215–218. ISBN 1-55581-142-6.
[ 14 ] Explainer – bacterial structure : https://youtu.be/fzIKJpcfXfo
[ 17 ] Human Urinary Composition Controls Antibacterial Activity of Siderocalin : Robin R. Shields-Cutler et al : From the Division of Infectious Diseases, Department of Medicine, Center for Women's Infectious Disease Research, and Department of Internal Medicine, Washington University School of Medicine. June 26, 2015 The Journal of Biological Chemistry 290, 15949-15960.
[ 18 ] The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine. Ferrières L., Hancock V., Klemm P. Microbiology 2008 154:167–175.
[ 19 ] Integrin-like Allosteric Properties of the Catch Bond-forming FimH Adhesin of Eschericia coli. Veronica Tchesnokova et al, University of Washington. March 21, 2008. The Journal of Biological Chemistry, 2008, 283,7823-7833 (Full Vesion)
[ 20 ] Induction of Gene Expression in Escjericia coli After Pilus-Mediated Adherance. Zhang, Jian Ping; Normark, Staffan. Science; Washington 273.5279 (Aug 30, 1996): 1234.
[ 21 ] The classical complement pathway plays a critical role in the opsonisation of uropathogenic Escherichia coli. Li K1, Sacks SH, Sheerin NS. Mol Immunol. 2008 Feb;45(4):954-62. Epub 2007 Sep 17.
[ 22 ] Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication. Kidney Int. 2004;65:791. Bates JM, Raffi HM, Prasadan K, Mascarenhas R, Laszik Z, Maeda N, et al.
[ 23 ] Tamm-Horsfall Protein Protects Against Urinary Tract Infection by Proteus mirabilis Hajamohideen S. Raffi, James M. Bates, Jr., Zoltan Laszik, and Satish Kumar‡ J Urol. 2009 May; 181(5): 2332–2338. Published online 2009 Mar 19. doi: 10.1016/j.juro.2009.01.014
[ 24 ] Type 1 Fimbrial Adhesin FimH Elicits an Immune Response That Enhances Cell Adhesion of Escherichia coli † Veronika Tchesnokova1 Pavel Aprikian1, Dagmara Kisiela1, Sarah Gowey1, Natalia Korotkova1, Wendy Thomas2 and Evgeni Sokurenko1*1 Department of Microbiology 2Department of Bioengineering, University of Washington, Seattle, Washington 98195 Infect. Immun. October 2011 vol. 79 no. 10 3895-3904
[ 25 ] Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation Drew J. Schwartza, Vasilios Kalasa, Jerome S. Pinknera, Swaine L. Chenb,c, Caitlin N. Spauldinga, Karen W. Dodsona, and Scott J. Hultgrena,1 August 12, 2013 Proceedings of the National Academy of Sciences of the United States of America PNAS vol. 110 no. 39, Drew J. Schwartz, 15530–15537
[ 26 ] World's most threatening superbugs ranked in new list By Michelle Roberts, Health editor, BBC News online, 27th Feb 2017
[ 27 ] Biofilm exclusion of uropathogenic bacteria by selected asymptomatic bacteriuria Escherichia coli strains. Ferrières L., Hancock V., Klemm P. Microbiology, 2007. 153:1711–1719.
Sweet Cures ’ Anna talks about her battle with cystitis. Read More
If you suffer from bladder pain or urinary tract infections, Waterfall Dmannose is the fast and all natural way to treat cystitis.
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