Mortality from MRSA Pneumonia Following Influenza Caused by Immune Mechanisms

Mortality from MRSA Pneumonia Following Influenza Caused by Immune Mechanisms

Influenza patients who get pneumonia caused by the superbug known as MRSA, (methicillin-resistant staphylococcus aureus) die from tissue damage caused by their own immune cells, rather than from direct consequences of bacterial infection.

The study, “Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia,” published in the Journal of Experimental Medicine, proposes that blocking this response might help to treat flu patients who get MRSA which currently leads to death in about half of infected patients.

Researchers have until now not understood why the mortality rate after such infections is so high, even though patients are treated with antibiotics that can usually get rid of the dangerous pathogen.

During earlier studies, researchers led by Keer Sun, an assistant professor at the University of Nebraska Medical Center, discovered why mice infected with influenza are more likely to get MRSA-caused pneumonia.

Normally, immune cells called macrophages and neutrophils kill bacteria by releasing hydrogen peroxide and other reactive oxygen species. This particular mechanism was suppressed in mice who had influenza and then got MRSA, but the finding did not explain why patients died despite treatment.

In the recent study, Sun and his team discovered that the immune cells not only lost their activity to kill the bacteria, but the initial increase in oxidative damage actually killed the immune cells. This action further aggravated the release of radical oxygen species from the dying cells and caused extensive tissue damage in the lungs of mice infected with both influenza virus and MRSA.

When researchers blocked the enzyme called Nox2 (nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2) that produces the oxidizing agents in macrophages and neutrophils, the damage became limited. Combining antibiotics that could kill MRSA with the compound blocking Nox2 also improved the survival of the mice.

“Our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation,” said Sun in a news release.

“This not only leads to increased susceptibility to MRSA infection but also extensive lung damage. Treatment strategies that target both bacteria and reactive oxygen species may significantly benefit patients with influenza complicated MRSA pneumonia,” he said.

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