An acquired acyltransferase promotes Klebsiella pneumoniae ST258 respiratory infection
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Author
Ahn, DanielleBhushan, Gitanjali
McConville, Thomas H.
Annavajhala, Medini K.
Soni, Rajesh Kumar
Wong Fok Lung, Tania
Hofstaedter, Casey E.
Shah, Shivang S.
Chong, Alexander M.
Castano, Victor G.
Ernst, Robert K.
Uhlemann, Anne Catrin
Prince, Alice
Date
2021-06-01Journal
Cell ReportsPublisher
Elsevier B.V.Type
Article
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Klebsiella pneumoniae ST258 is a human pathogen associated with poor outcomes worldwide. We identify a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation of these organisms in vivo. Comparison of a wild-type ST258 strain (KP35) and a Δatf3 isogenic mutant generated by CRISPR-Cas9 targeting reveals greater NADH:ubiquinone oxidoreductase transcription and ATP generation, fueled by increased glycolysis. The acquisition of atf3 induces changes in the bacterial acetylome, promoting lysine acetylation of multiple proteins involved in central metabolism, specifically Zwf (glucose-6 phosphate dehydrogenase). The atf3-mediated metabolic boost leads to greater consumption of glucose in the host airway and increased bacterial burden in the lung, independent of cytokine levels and immune cell recruitment. Acquisition of this acyltransferase enhances fitness of a K. pneumoniae ST258 isolate and may contribute to the success of this clonal complex as a healthcare-associated pathogen. © 2021 The AuthorsIdentifier to cite or link to this item
http://hdl.handle.net/10713/15955ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2021.109196