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Serendipity Contributes to MRSA Susceptibility Findings

Duke University Medical Center researchers have found two genes in mice which might help identify why some people are more susceptible than others to potentially deadly staph infections.

The researchers uncovered important genetic clues that ultimately could help inform patient management and drug development.

"If you know up front that a patient is at risk for developing an Staphylococcus aureus infection, then you will be better able to manage them clinically, give them preventive measures, and treat them more aggressively if they become ill," said Vance Fowler, M.D., MHS, an associate professor of infectious diseases in the Duke Department of Medicine. MRSA is a severe form of the infection, methicillin-resistant Staphylococcus aureus.

Knowing more about the genetics would give a heightened awareness of individual susceptibility for a condition that injures and kills many people each year, and that is no longer just confined to intensive care units and hospitals, he said.

Knowing about genetic susceptibility could also help to uncover the pathways involved in how host and pathogen interact, Fowler said.

The discovery of two highly promising susceptibility genes happened because just the right mice for this inquiry were available.

"We think this study was a real win," Fowler said. "However, it also goes to show that sometimes it's better to be lucky than good."

Scientists had observed that two strains of laboratory mice had different courses of Staphylococcus aureus (SA) infection, one susceptible to severe infections (A/J) and one that was resistant and had much milder infections(C57BL/6J or C57). These two mouse strains had been further modified, so that the more-resistant C57 mice were bred to contain both versions of one chromosome from the susceptible A/J strain. These modified mice were commercially available at Jackson Labs.

"This lucky break allowed us to narrow our search for genes governing susceptibility to S. aureus from 21 chromosomes to just three." Fowler said. "We finally narrowed the search to two genes on chromosome 18 and were able to show that each of these genes appears to influence the immune response to S. aureus."

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