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Lactobacillus murinus Reduces Susceptibility to Secondary MRSA Infection in IAV-Infected Mice Through Promoting a T
Qichao Chen1, Yanfeng Lin2, Kaiying Wang2
1Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, China.
Abstract:
Secondary methicillin-resistant Staphylococcus aureus (MRSA) infection causes high mortality in patients with influenza A virus (IAV). Our previous study observed that the relative abundance of Lactobacillus murinus (L. murinus) was significantly reduced in both the respiratory tract and gut of IAV-infected mice and negatively correlated with the severity of IAV-MRSA coinfection pneumonia, but the role of L. murinus remains unclear. Here, we supplemented the respiratory tract and gut of IAV-infected mice with live L. murinus and performed a secondary MRSA infection challenge to investigate the effects and potential mechanisms further. Data showed that L. murinus supplementation significantly reduced mortality and pathogen loads in IAV-MRSA coinfected mice and upregulated the lung T cell-independent (TI) IgA response in IAV-infected mice. The 16S rRNA gene sequencing results showed that L. murinus supplementation ameliorated microbiota composition disorder and regulated metabolic dysfunction in the gut of IAV-infected mice. The correlation analysis and antibiotic cocktail treatment experiment showed that the TI IgA response in lungs is dependent on gut microbiota. These findings demonstrated that L. murinus supplementation reduces susceptibility to secondary MRSA infection in IAV-infected mice by promoting the TI IgA response, and provide a new perspective on the use of probiotics to prevent secondary bacterial infection following IAV infection.
Insights
Lactobacillus murinus supplementation reduced mortality in mice coinfected with influenza A virus and MRSA. This probiotic intervention enhanced lung immunity and gut microbiota, offering a new strategy against secondary bacterial infections.
Area of Science:
- Microbiology
- Immunology
- Virology
Background:
- Secondary methicillin-resistant Staphylococcus aureus (MRSA) infections significantly increase mortality in patients with influenza A virus (IAV).
- Previous research indicated reduced Lactobacillus murinus abundance in IAV-infected mice, correlating with coinfection severity, but its protective role was undetermined.
Purpose of the Study:
- To investigate the effects of Lactobacillus murinus supplementation on IAV-MRSA coinfection in mice.
- To elucidate the potential mechanisms underlying L. murinus's protective role against secondary bacterial pneumonia.
Main Methods:
- Supplementation of live L. murinus to the respiratory tract and gut of IAV-infected mice.
- Secondary challenge with MRSA to assess coinfection outcomes.
- Analysis of mortality, pathogen loads, lung immune responses (TI IgA), gut microbiota composition (16S rRNA sequencing), and metabolic function.
Main Results:
- L. murinus supplementation significantly reduced mortality and pathogen loads in IAV-MRSA coinfected mice.
- Supplementation upregulated the T cell-independent (TI) IgA response in the lungs of IAV-infected mice.
- L. murinus ameliorated gut microbiota dysbiosis and metabolic dysfunction, with TI IgA shown to be gut microbiota-dependent.
Conclusions:
- L. murinus supplementation mitigates susceptibility to secondary MRSA infection in IAV-infected mice.
- The protective effect is mediated by promoting lung TI IgA responses, which are influenced by gut microbiota.
- L. murinus represents a potential probiotic strategy for preventing secondary bacterial infections post-IAV.
