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

Atul K. Verma, Christopher Bauer, Vijaya Kumar Yajjala, Shruti Bansal, Keer Sun

Research output: Contribution to journalArticle

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-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.

Original languageEnglish (US)
JournalInfection and immunity
Volume87
Issue number10
DOIs
StatePublished - Oct 1 2019

Fingerprint

Linezolid
Staphylococcal Pneumonia
Methicillin-Resistant Staphylococcus aureus
Lung
Anti-Bacterial Agents
Therapeutic Uses
Vancomycin
Coinfection
Mortality
Therapeutics
Orthomyxoviridae
Sputum
L-Lactate Dehydrogenase
Human Influenza
Proteins
Cytokines

Keywords

  • alpha-toxin
  • antibiotic therapy
  • coinfection
  • influenza
  • MRSA
  • pneumonia

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia. / Verma, Atul K.; Bauer, Christopher; Yajjala, Vijaya Kumar; Bansal, Shruti; Sun, Keer.

In: Infection and immunity, Vol. 87, No. 10, 01.10.2019.

Research output: Contribution to journalArticle

Verma, Atul K. ; Bauer, Christopher ; Yajjala, Vijaya Kumar ; Bansal, Shruti ; Sun, Keer. / Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia. In: Infection and immunity. 2019 ; Vol. 87, No. 10.
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