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Gastric ulcer bacteria hide from the immune system

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A while ago, I wrote about how Helicobacter pylori, the bacteria that cause stomach ulcers and are implicated in certain stomach cancers, cause the cells of the stomach wall to die. H. pylori kills cells very sneakily, by releasing a chemical that causes them to commit suicide. It turns out that this is not the only sneaky trick H. pylori has, it can also hide from the immune system by changing its outer cell membrane.

The immune system protects your body from any invading elements, and because of this it needs a way to distinguish body cells from invading cells. The cells of the immune system do this by recognising bits of bacteria as foreign invaders, and of course the first bit of the bacteria they see is the outer cell membrane. H. pylori has a way of making parts of its outer cell membrane look very similar to human blood group antigens, so the immune cell doesn’t recognise it as an invader.

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The bacterial cell membrane is made up of lipopolysaccharides (i.e lipids, or fats, connected to polysaccharides - sugars). H. pylori has ways to modify the biosynthesis pathway of these lipopolysaccharides to produce different structures. In particular to lipid A, which is part of the structure on the surface of H. pylori.

The bacteria have several different ways that they modify the lipid A. Firstly, they can reduce the lipids overall negative charge, either by adding positively charged substrates, or by removing negatively charged phosphate groups. This makes the bacteria more resilient to certain antimicrobial peptides that bind to negative charges. They can also add extra bits to the lipid A (in particular acyl groups) which make the surface of the  bacteria harder to for immune cells to recognise. This lipid A modification pathway is highly ordered and efficient. Rather than producing all different kinds of lipid A at the surface, each bacterium will be covered in one type of modified lipid  A.

Lipid A from E. coli, with the phosphate groups circled in red. Image credit below.

The reason that H. pylori has this one specific modification pathway is likely  to be due to the fact that it only has one host. H. pylori lives in humans and nowhere else. There is only one type of immune system it has to evade. Once the lipid A resembles human blood antigens, any changes or alterations would be strongly selected against in order to keep the bacteria well hidden.

For a more in-depth biochemical analysis of exactly how these modifications happen, take a look at the paper below!

Credit for image 2

Ref 1: Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, & Trent MS (2011). Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS pathogens, 7 (12) PMID: 22216004

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. connorGGbamford 2:38 pm 02/26/2012

    Really nice post – and paper! I was wondering, if H.pylori lives in your stomach, what is this stomach immune system like? I never really think of it having one as such. Just a lot of acid! Is this bacteria hiding from cells in particular? Stomach cells? Or certain immune cells??

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  2. 2. Bops 8:30 pm 02/26/2012

    There are so many people with stomach acid and other problems.
    The article was interesting. thanks.

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  3. 3. S.E. Gould in reply to S.E. Gould 4:27 am 02/28/2012

    There aren’t many immune cells actually floating around in the stomach because of the low pH, but this particular defence mechanism means that if any part of the bacteria happens to get anywhere near any immune cells (it’ll be the white blood cells, macrophages in particular that it’s hiding from) it won’t register on the radar. The stomach wall is lined with mucus, which macrophages can travel around in when they need too, and there are various enzymes and antibodies that can also reach the stomach through the mucus layer.

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