The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia.

Cell reports 2022

["Langou\u00ebt-Astri\u00e9 C", "Oshima K", "McMurtry S", "Yang Y", "Kwiecinski J", "LaRivi\u00e8re W", "Kavanaugh J", "Zakharevich I", "Hansen K", "Shi D"]

Abstract

Influenza infection is substantially worsened by the onset of secondary pneumonia caused by bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). The bidirectional interaction between the influenza-injured lung microenvironment and MRSA is poorly understood. By conditioning MRSA ex vivo in bronchoalveolar lavage fluid collected from mice at various time points of influenza infection, we found that the influenza-injured lung microenvironment dynamically induces MRSA to increase cytotoxin expression while decreasing metabolic pathways. LukAB, a SaeRS two-component system-dependent cytotoxin, is particularly important to the severity of post-influenza MRSA pneumonia. LukAB’s activity is likely shaped by the post-influenza lung microenvironment, as LukAB binds to (and is activated by) heparan sulfate (HS) oligosaccharide sequences shed from the epithelial glycocalyx after influenza. Our findings indicate that post-influenza MRSA pneumonia is shaped by bidirectional host-pathogen interactions: host injury triggers changes in bacterial expression of toxins, the activity of which may be shaped by host-derived HS fragments.

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