Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia

Infection and Immunity
Atul K VermaKeer Sun

Abstract

Postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treat...Continue Reading

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Citations

Jul 11, 2020·Clinical Science·Ellyse M CipollaJohn F Alcorn
Dec 19, 2019·Frontiers in Pharmacology·Jin WangYun Cai
Oct 13, 2020·Frontiers in Cellular and Infection Microbiology·Christina CahillJoseph Keane
Aug 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Atul K VermaKeer Sun
Oct 8, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Andrea SauerChristian Bode

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