ArticleThe Journal of experimental medicine2016
Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Omadacycline exhibits anti-inflammatory properties and improves survival in a murine model of post-influenza MRSA pneumonia.Antimicrobial agents and chemotherapy · 2025Article
- A Tale of Two Cytokines: IL-10 Blocks IFN-γ in Influenza A Virus-American journal of respiratory cell and molecular biology · 2024Article
- IL-10 Counteracts IFN-γ to Alleviate Acute Lung Injury in a Viral-Bacterial Superinfection Model.American journal of respiratory cell and molecular biology · 2024Article
- Detection of blaBMC microbiology · 2024Article
- Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.The Journal of clinical investigation · 2023Article
- Pathogenesis of Respiratory Viral and Fungal Coinfections.Clinical microbiology reviews · 2022Review
- The role of oxidative stress in the pathogenesis of infections with coronaviruses.Frontiers in microbiology · 2022Review
- IFN-γ transforms the transcriptomic landscape and triggers myeloid cell hyperresponsiveness to cause lethal lung injury.Frontiers in immunology · 2022Article
- Disease Tolerance during Viral-Bacterial Co-Infections.Viruses · 2021Review
- Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model.Antioxidants (Basel, Switzerland) · 2021Article
- Shooting yourself in the foot: How immune cells induce antibiotic tolerance in microbial pathogens.PLoS pathogens · 2021Review
- Outcomes of respiratory viral-bacterial co-infection in adult hospitalized patients.EClinicalMedicine · 2021Article
- When two for the price of one isn't a bargain: estimating prevalence and microbiology of bacterial co-infections in patients with COVID-19.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2020Article
- Bacterial co-infections with SARS-CoV-2.IUBMB life · 2020Review
- The Antioxidant Rosmarinic Acid Ameliorates Oxidative Lung Damage in Experimental Allergic Asthma via Modulation of NADPH Oxidases and Antioxidant Enzymes.Inflammation · 2020Article
- Phosphodiesterase 4 inhibitors attenuate virus-induced activation of eosinophils from asthmatics without affecting virus binding.Pharmacology research & perspectives · 2020Article
- Targeting Evolutionary Conserved Oxidative Stress and Immunometabolic Pathways for the Treatment of Respiratory Infectious Diseases.Antioxidants & redox signaling · 2020Review
- Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection.Nature microbiology · 2020Article
- Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia.Infection and immunity · 2019Article
- Novel endosomal NOX2 oxidase inhibitor ameliorates pandemic influenza A virus-induced lung inflammation in mice.Respirology (Carlton, Vic.) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.