MassIVE MSV000087181

Partial Public PXD025326

An Acquired Acyltransferase Promotes Klebsiella pneumoniae ST258 Respiratory Infection

Description

Klebsiella pneumoniae ST258 are human pathogens associated with poor outcomes in patients worldwide. We identified a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation of this group of organisms in vivo. Comparison of a wild type ST258 strain (KP35) and a atf3 isogenic mutant generated by Crispr-Cas9 targeting, revealed increased NADH:quinone oxidoreductase transcription and ATP generation, fueled by increased glycolysis. Acquisition of atf3 induced changes in the bacterial acetylome, promoting lysine acetylation of multiple gene products involved in central metabolism, specifically Zwf (glucose-6 phosphate dehydrogenase). The atf3-mediated metabolic boost led 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 a promiscuous acyltransferase enhances K. pneumoniae ST258 fitness and promotes its emergence as a major health care associated pathogen. [doi:10.25345/C5JZ38] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Klebsiella pneumoniae

Contact

Principal Investigators:
(in alphabetical order)
Danielle Ahn, Columbia University - Department of Pediatrics, USA
Submitting User: rs3869
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