Helicobacter pylori, one of the world's most widespread pathogenic human colonizers, has revealed to researchers another of its survival secrets—one that experts hope might help in the search for prophylactic measures against the nefarious microbe.

H. pylori inhabits the stomach lumen of more than half the people on earth, a finding itself so startling that Robin Warren and Barry Marshall received a Nobel Prize in 2005 for discovering the bug and overturning the long-held erroneous dogma that the stomach is too inhospitable for microbial inhabitants. The success of H. pylori is largely a result of its stealth; the bacteria are able to persist for decades because of their many techniques for avoiding the host immune system. They are, however, far from innocuous, damaging the stomach with gastic cancer and ulcers.

Although H. pylori infection is treatable with antibiotics, even the most effective therapies achieve only 80% eradication and often require cocktails of two antibiotics and a bismuth compound. This refractory nature of H. pylori infection has spurred researchers to study the microbe more closely.

In this context, Thomas Meyer at the Max Planck Institute for Infection Biology (Berlin, Germany) and his colleagues recently stumbled upon one of H. pylori's host-evasion strategies while investigating one of the bacteria's metabolic needs: cholesterol. H. pylori are not able to synthesize cholesterol and must obtain it from their environment—the stomach.

Meyer and coworkers discovered that H. pylori extracts cholesterol right from the plasma membrane of the stomach's epithelial cells, but in so doing lit upon the strange fact that mice infected with mouse-adapted H. pylori and fed a 2% cholesterol diet cleared 95% of their infection after 25 weeks, a phenomenon not seen in control mice fed a cholesterol-free diet (Nature Med., September).

These results beg the question: does dietary cholesterol improve immune response to H. pylori? Indeed, this seems to be the case; the stomachs of cholesterol-fed mice revealed immune-cell infiltration absent in controls. But there's a twist: H. pylori appears to have developed a mechanism for protecting itself from this cholesterol-mediated immune detection. Meyer's team found that H. pylori chemically alters most of that cholesterol before incorporating it into its own plasma membrane, disguising the molecule from host immune cells. In fact, mice infected with H. pylori mutants deficient for the cholesterol-conversion enzyme resolved their infections within 48 hours.

Christian Wunder, one of the paper's first authors, tells Lab Animal that he hopes targeting the cholesterol-conversion enzyme will allow the creation of a “new kind of antibiotic, one that is neither bacteriostatic nor bactericidal by classical definition, but that renders the pathogen accessible to the immune system.”