Respiratory Commensal Bacteria Increase Protection Against Hypermucoviscous Carbapenem-Resistant ST25 Infection

In a previous work, we demonstrated that nasally administered 090104 beneficially modulated the respiratory innate immune response and improved the protection against Respiratory Syncytial Virus and in mice. In this work, we aimed to evaluate whether the immunomodulatory 090104 strain was able to enhance the resistance against the respiratory infection induced by hypermucoviscous carbapenemase-producing (KPC-2) strains belonging to the sequence type (ST) 25. The nasal treatment of mice with 090104 before the challenge with multiresistant ST25 strains significantly reduced lung bacterial cell counts and lung tissue damage. The protective effect of the 090104 strain was related to its ability to regulate the respiratory innate immune response triggered by challenge. 090104 differentially modulated the recruitment of leukocytes into the lung and the production of TNF-α, IFN-γ and IL-10 levels in the respiratory tract and serum. Our results make an advance in the positioning of 090104 as a next-generation probiotic for the respiratory tract and encourage further research of this bacterium as a promising alternative to develop non-antibiotic therapeutical approaches to enhance the prevention of infections produced by microorganisms with multiple resistance to antimicrobials such as KPC-2-producing hypermucoviscous strains belonging to ST25.