A hereditary genetic tendency seems to increase the possibility that an individual can effectively fight off antibiotic-resistant staph infections, as per a study led by Duke Health researchers.
The finding includes significant insights into the hereditary factors that incline a few people to persistent methicillin-resistant Staphylococcus aureus (MRSA) infections and could result in the development of better treatment options.
“The growing prevalence of antibiotic-resistant staph infections has created an urgent need to more likely comprehend who is most susceptible to these difficult-to-treat S. aureus infections and why,” said Vance Fowler, M.D., professors in the departments of Medicine and Molecular Genetics and Microbiology at Duke. Fowler is senior author of a study appearing the week of Sept. 16 in the Proceedings of the National Academy of Sciences.
“This study provides solid proof of a genetic variant that seems to help individuals with MRSA to resolve their bloodstream infections,” Fowler said.
Fowler and colleagues analyzed two closely matched sets of patients by age, sex, health conditions and other risk factors for MRSA bloodstream infections. Sixty-eight patients were identified; half had a persistent MRSA infection and half had been able to clear the infection from their circulation system.
They ran whole-exome sequencing on the patients and found a genetic variation that was obvious in about 62% of the patients who cleared an MRSA infection vs. just 9% in the individuals who had persistent infections.
This hereditary mutation—located in the DNMT3A region of chromosome 2p—seems to enable a patient’s immune response to more readily resolve their MRSA bloodstream infection.
One of the immune components the DNMT3A mutation seems to affect is IL-10, an anti-inflammatory cytokine that reduces the host’s response to S. aureus infection. Researchers have discovered that while the appropriate amount of IL-10 is critical to regulating host action, a lot is associated with tissue damage and even death.
Among the individuals who had the gene mutation, serum levels of IL-10 remained in check, recommending that the host immune response was thus better able to clear the MRSA infection.
The researchers tested the finding in animal models by hindering methylation of the regulatory gene, which prompted increased susceptibility to a staph infection.
“Our study identifies a specific DNMT3A mutation that adds to an increased ability to resolve MRSA infections,” Fowler said. “The mechanism for this appears to be increased methylation of gene regulatory regions, and reduced levels of the anti-inflammatory cytokine IL-10.”