Researchers at the University of Nebraska Medical Center have found that secondary infection with the methicillin-resistant Staphylococcus aureus (MRSA) bacterium often kills influenza patients because the flu virus alters the antibacterial response of leukocytes, causing them to damage the patients’ lungs instead of destroying the bacterium. The study, which was published online in the Journal of Experimental Medicine, suggests that inhibiting this response may help treat patients infected with both the flu virus and MRSA.
Many influenza patients develop severe pneumonia as a result of secondary infections with MRSA. Over half of these patients die, even when treated with antibiotics that are usually capable of clearing MRSA infections. Lead investigator Dr. Keer Sun previously discovered that mice infected with influenza are susceptible to MRSA because the ability of their macrophages and neutrophils to kill bacteria by releasing hydrogen peroxide and other reactive oxygen species is suppressed. But it remained unclear why MRSA-infected influenza patients often die, even after receiving appropriate antibiotic treatment.
Sun and his colleagues have found that this may be because the patients’ leukocytes cause extensive damage to their lungs. Although the macrophages and neutrophils of mice coinfected with influenza and MRSA were defective at killing bacteria, reactive oxygen species released by these cells induced the death of inflammatory cells within the lungs, lethally damaging the surrounding tissue. Inhibiting NADPH oxidase 2 (Nox2), the enzyme that produces reactive oxygen species in macrophages and neutrophils, reduced the extent of this damage and, when combined with antibiotic treatment, boosted the survival of coinfected mice.
“Our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation,” Sun said. “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.”
Source: EurekAlert; August 15, 2016.