Genetic underpinnings of severe staph infections

A common culprit of skin and respiratory infections, Staphylococcus aureus is highly unpredictable. Between 20 and 30 percent of people carry quiet colonies on their skin and in their nostrils, which seldom cause problems beyond the occasional rash. But in some cases these bacteria cause infections that lead to deadly complications, such as pneumonia, deep skin infections, and sepsis. Until recently, there was no way to predict which infections may take a lethal turn.

Now, a new study describes mutations that predispose patients to severe staphylococcal infections. The research, published in Science, identifies a mutated gene common to multiple patients who suffer life-threatening staph infections and suggests that people living with a genetic condition known as 5p- or Cri-du-chat syndrome may be at similar risk.

“We have characterized severe Staphylococcus aureus infection at the genetic, cellular, immunological, and clinical levels,” says András Spaan, first author on the study. “By integrating these levels, we have established causality and provided clues for future interventions.”

A first for cell intrinsic immunity

To better understand why S. aureus causes disease in some people but not others, scientists in the laboratory of Rockefeller immunologist Jean-Laurent Casanova examined the protein-coding genomes of more than 100 patients who had suffered from unexplained severe staph infections.

The common genetic thread linking some of these disparate patients were mutations of a gene called OTULIN, which is perched along the short arm of chromosome 5 and codes for an enzyme involved in regulating inflammation. These individuals were not entirely bereft of OTULIN — only one of their two copies of the gene was mutated — but that deficiency appeared to be all it took to render them vulnerable to infections that would scarcely harm other people.

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