MAY 20, 2022 1:02 PM PDT

Why Staph Infections are Only Severe for Some

WRITTEN BY: Carmen Leitch

Bacteria live all around us, even in us. Though some bacterial pathogens can cause dangerous infections, many of those microbes are harmless. Sometimes, the same strain of bacteria can lead to very different outcomes. Staphylococcus aureus is one example; it can live harmlessly in the respiratory tracts of many people. But for others, staph can cause skin and respiratory infections, and those infections can lead to severe and occasionally fatal complications including pneumonia and sepsis.

A digitally colorized SEM image of mustard-colored, methicillin-resistant, Staphylococcus aureus (MRSA) bacteria, surrounded by orange-colored cellular debris./ Credit: National Institute of Allergy and Infectious Diseases (NIAID)

Researchers have now learned more about why staph infections turn deadly in some cases. The portion of the genome that codes for proteins is known as the exome. In this study, the researchers assessed the exomes of over 100 patients with severe, unexplained Staph infections. Reporting in Science, they have discovered genetic mutations in humans that can increase their risk of serious staph infections. One mutant gene is found in a variety of patients with life-threatening staph infections, and the scientists determined that people with a disorder known as 5p- or Cri-du-chat could also have an elevated risk.

Mutations in the OTULIN gene, which encodes for an enzyme that is involved in inflammation regulation, were found in these patients. The mutation caused a deficiency in the enzyme's activity, which appeared to be enough to make carriers vulnerable to severe infections.

The researchers determined that mutations in OTULIN indirectly lead to the accumulation of another protein on the surfaces of lung and skin cells, which impairs a process called intrinsic immunity; then the cells can't deal with the effects of a toxin that staph produces.

Problems with cell intrinsic immunity have been shown to predispose people to some viral infections, but this is the first time it's been shown to have a connection to a bacterial infection.

Individuals carrying one mutated copy of the OTULIN gene may be predisposed to infection, but those without any functional OTULIN often don't survive past the first year of life because they have so many early-onset inflammatory issues. "People with two functional copies of the gene appear to be healthy, those with no functional copies have autoinflammatory disease, and those with one functional copy are susceptible to severe staph infections," explained first study András Spaan.

A disorder called 5p- syndrome is a chromosomal deletion disorder, in which the short arm of chromosome 5, where OTULIN is located, is lost. The disorder leads to developmental delays and intellectual disabilities. When 5p- syndrome patients were examined, the researchers determined that one-third of them are susceptible to lung infections, and that vulnerability appears to be caused by the loss of OTULIN.

"In many ways, these patients looked genetically similar to the patients we had identified with severe staph infections," said Spaan.

The researchers cautioned that not everyone with OTULIN mutations or 5p- syndrome will get serious infections. It's still unclear why not all genetic mutations manifest in the same way in all people. It may have to do with the interplay of other genes, epigenetic effects, environmental influences, or some other factors. More research will be focused on learning more about that phenomenon.

In this case, the researchers found that some individuals that carry OTULIN mutations but don't have severe disease symptoms also had high levels of Staph toxin-neutralizing antibodies. People with severe disease had low levels of those antibodies.

Sources: Rockefeller University, Science

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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