Shape is also important, for H. pylori

27 May 2010

Scientists have shown that the corkscrew-like shape of the bacterium Helicobacter pylori (H. pylori), is critical to the ability of this pathogen to cause stomach ulcers and gastric cancer.

The discovery that the H. pylori bug is the cause of almost all cases of stomach ulcers won the 2005 Nobel Prize for the two Australian researchers who first identified it in the early 1980s, Barry Marshall and Robin Warren.  But how and why this bug adopts the strange spiral configuration that it does has remained a mystery.

Electron micrograph of H. pylori possessing multiple flagella (negative staining)The trait is strongly conserved amongst all strains of the bacterium carried by humans, arguing that it must play an important role in the pathogenicity or persistence of the bacterium.  It might therefore also provide a bacterial Achilles heel which microbiologists can exploit to neutralise this bug, which is carried by about half the population.

Now scientists in Seattle have identified the genes that give the bug its shape and, by knocking them out, confirmed that, without this corkscrew configuration, the bug struggles to gain a toehold.

Writing in Cell, Nina Salama at Fred Hutchinson Cancer Research Center and her colleagues explain how they screened colonies of the bacteria looking for mutants lacking the characteristic twisted shape and then hunted for the genes that had been changed to produce the effect.  They found three: csd1, csd2, csd3 and cmmA which, when "knocked out" prevented the bugs from adopting their normal configuration.

Surprisingly, this didn't appear to compromise the swimming ability of the bacteria nor, as some had expected, their ability to drill their way through thick mucus, which is how it was believed the agents cling to the stomach wall.  But when the team fed the mishapen bugs to experimental mice they found that, compared with wild-type bacteria the mutants struggled for survival.  Analysing the function of the genes shows that they work by clipping certain sections of the mesh-like outer cell wall of the bacterium, which makes the rod-shaped bacterium form a spiral.

The fact that disabling this system compromised the bugs so severely suggests that it might represent a powerful way to tackle these infections - and those caused by other similarly-shaped organisms including campylobacters and vibrio (cholera) - in future.


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