Journal article
Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection
T Wong Fok Lung, D Charytonowicz, KG Beaumont, SS Shah, SH Sridhar, CL Gorrie, A Mu, CE Hofstaedter, D Varisco, TH McConville, M Drikic, B Fowler, A Urso, W Shi, D Fucich, MK Annavajhala, IN Khan, I Oussenko, N Francoeur, ML Smith Show all
Cell Metabolism | CELL PRESS | Published : 2022
Abstract
K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflamm..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Dr. J. Kwintkiewicz (TECAN) for technical support with the customized Universal Prokaryotic RNA-seq library preparation kit. This work was supported by NIH grants 1R35HL135800 to A.P.; K99 HL157550 to T.W.F.L.; K08 HL138289 to D.A.; T32 AI100852-04 and K08 AI146284 to T.H.M.; R01AI116939 (NIAID) to A.-C.U.; NCI P01CA87497, NCI R35CA209896, NINDS R61NS109407, and NINDS R33NS109407 to B.R.S. and NHMRC Investigator grant (Australia) APP1196103 to B.P.H. This study was also supported by NIH grant S10RR027050 to the Columbia Center for Translational Immunology (CCTI) Flow Cytometry Core, NIH (NCI) grant P30CA013696 to the Molecular Pathology Shared Resource (MPSR) of the Herbert Irving Comprehensive Cancer Center at Columbia University, and NIH (CTSA) grant UL1TR001873 to the Single Cell Analysis Core at the JP Sulzberger Columbia Genome Center. The Calgary Metabolomics Research Facility (CMRF) is supported by the International Microbiome Centre and the Canada Foundation for Innovation (CFI-JELF 34986). I.A.L is supported by an Alberta Innovates Translational Health Chair. The graphical abstract was created with https://biorender.com/.