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.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
About The Expert
Danielle Ahn
Gitanjali Bhushan
Thomas H McConville
Medini K Annavajhala
Rajesh Kumar Soni
Tania Wong Fok Lung
Casey E Hofstaedter
Shivang S Shah
Alexander M Chong
Victor G Castano
Robert K Ernst
Anne-Catrin Uhlemann
Alice Prince
References
PubMed