The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia.

Autor:	Langouët-Astrié C; Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: christophe.langouetastrie@cuanschutz.edu., Oshima K; Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Aurora, CO 80045, USA., McMurtry SA; Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Aurora, CO 80045, USA., Yang Y; Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Aurora, CO 80045, USA., Kwiecinski JM; Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow 30387, Poland., LaRivière WB; Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Aurora, CO 80045, USA; Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045, USA., Kavanaugh JS; Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Zakharevich I; Department of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO 80045, USA., Hansen KC; Department of Biochemistry and Molecular Genetics, University of Colorado, Aurora, CO 80045, USA., Shi D; Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12180, USA., Zhang F; Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12180, USA., Boguslawski KM; Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA., Perelman SS; Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA., Su G; University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA., Torres VJ; Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA., Liu J; University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA., Horswill AR; Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Schmidt EP; Division of Pulmonary Sciences and Critical Care, University of Colorado Denver, Aurora, CO 80045, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02115, USA.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Nov 29; Vol. 41 (9), pp. 111721.
DOI:	10.1016/j.celrep.2022.111721
Abstrakt:	Influenza infection is substantially worsened by the onset of secondary pneumonia caused by bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). The bidirectional interaction between the influenza-injured lung microenvironment and MRSA is poorly understood. By conditioning MRSA ex vivo in bronchoalveolar lavage fluid collected from mice at various time points of influenza infection, we found that the influenza-injured lung microenvironment dynamically induces MRSA to increase cytotoxin expression while decreasing metabolic pathways. LukAB, a SaeRS two-component system-dependent cytotoxin, is particularly important to the severity of post-influenza MRSA pneumonia. LukAB's activity is likely shaped by the post-influenza lung microenvironment, as LukAB binds to (and is activated by) heparan sulfate (HS) oligosaccharide sequences shed from the epithelial glycocalyx after influenza. Our findings indicate that post-influenza MRSA pneumonia is shaped by bidirectional host-pathogen interactions: host injury triggers changes in bacterial expression of toxins, the activity of which may be shaped by host-derived HS fragments. Competing Interests: Declaration of interests V.J.T. is also an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech, Inc. Janssen Biotech, Inc., provides research funding and other payments associated with a licensing agreement. V.J.T. has consulted for Janssen Research & Development and has received honoraria from Genentech and Medimmune. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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