Alveolar metabolite availability facilitates secondary infection by Pseudomonas aeruginosa in acutely injured lungs

Baker, J. M.; Flott, T. L.; McLellan, L. A.; Bustos, I. G.; Guerrero, J. L.; Mendez, L. M.; Petouhoff, A. M.; Ranjan, P.; Metcalf, J. D.; McDonald, R. A.; Falkowski, N. R.; He, Y.; Cala, M. P.; Huffnagle, G. B.; Sjoding, M. W.; Reyes, L. F.; Stringer, K. A.; Dickson, R. P.

doi:10.1101/2024.12.18.629020

bioRxiv · 10.1101/2024.12.18.629020

Alveolar metabolite availability facilitates secondary infection by Pseudomonas aeruginosa in acutely injured lungs

Baker, J. M.·Flott, T. L.·McLellan, L. A.·Bustos, I. G.·Guerrero, J. L.·Mendez, L. M.·Petouhoff, A. M.·Ranjan, P.·Metcalf, J. D.·McDonald, R. A.·Falkowski, N. R.·He, Y.·Cala, M. P.·Huffnagle, G. B.·Sjoding, M. W.·Reyes, L. F.·Stringer, K. A.·Dickson, R. P.

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Abstract

Secondary bacterial pneumonia is a frequent complication of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Prior efforts to explain increased pneumonia risk in ALI/ARDS have focused on impaired immunity and bacterial virulence, but have overlooked the potential contribution of ecological factors within acutely injured lungs. Here, we show that lung injury profoundly alters the alveolar metabolic microenvironment, a change that can be exploited by a common pneumonia pathogen. In mice and humans, we found that growth of Pseudomonas aeruginosa (the most prominent respiratory pathogen in a retrospective cohort of patients with ARDS) is enhanced by increased alveolar concentrations of multiple ALI/ARDS-associated metabolites, which are derived from the blood and cross the compromised alveolar-capillary barrier during alveolar leak. Collectively, this work reveals an ecological mechanism by which pathogens may survive in the injured lung microenvironment and identifies new potential targets for secondary pneumonia prevention and treatment.

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Baker, J. M., Flott, T. L., McLellan, L. A., Bustos, I. G., Guerrero, J. L., Mendez, L. M., Petouhoff, A. M., Ranjan, P., Metcalf, J. D., McDonald, R. A., Falkowski, N. R., He, Y., Cala, M. P., Huffnagle, G. B., Sjoding, M. W., Reyes, L. F., Stringer, K. A., Dickson, R. P.. 2025-01-04. Alveolar metabolite availability facilitates secondary infection by Pseudomonas aeruginosa in acutely injured lungs. https://doi.org/10.1101/2024.12.18.629020

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