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An Acquired Acyltransferase Promotes Klebsiella pneumoniae ST258 Respiratory Infection

48 Pages Posted: 20 Nov 2020 Publication Status: Published

See all articles by Danielle Ahn

Danielle Ahn

Columbia University - Department of Pediatrics

Gitanjali Bhushan

Columbia University - Department of Pediatrics

Thomas H. McConnville

Columbia University - Department of Medicine

Medini K. Annavajhala

Columbia University - Department of Medicine

Rajesh Kumar Soni

Columbia University - Proteomics and Macromolecular Crystallography Shared Resource

Tania Wong Fok Lung

Columbia University - Department of Pediatrics

Casey E. Hofstaedter

University of Maryland – Baltimore - Department of Microbial Pathogenesis

Shivang Shah

Columbia University - Department of Pediatrics

Alexander M. Chong

Columbia University - Department of Medicine

Victor G. Castano

Columbia University - Department of Pediatrics

Robert K. Ernst

University of Maryland – Baltimore - Department of Microbial Pathogenesis

Anne-Catrin Uhlemann

Columbia University - Department of Medicine

Alice Prince

Columbia University - Department of Pediatrics

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Abstract

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 Δatf3 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.

Keywords: bacterial pneumonia, glycolysis, metabolism, acetylation, Klebsiella pneumoniae, sequence type 258

Suggested Citation

Ahn, Danielle and Bhushan, Gitanjali and McConnville, Thomas H. and Annavajhala, Medini K. and Soni, Rajesh Kumar and Wong Fok Lung, Tania and Hofstaedter, Casey E. and Shah, Shivang and Chong, Alexander M. and Castano, Victor G. and Ernst, Robert K. and Uhlemann, Anne-Catrin and Prince, Alice, An Acquired Acyltransferase Promotes Klebsiella pneumoniae ST258 Respiratory Infection. Available at SSRN: https://ssrn.com/abstract=3734595 or http://dx.doi.org/10.2139/ssrn.3734595
This version of the paper has not been formally peer reviewed.

Danielle Ahn (Contact Author)

Columbia University - Department of Pediatrics ( email )

NY
United States

Gitanjali Bhushan

Columbia University - Department of Pediatrics ( email )

NY
United States

Thomas H. McConnville

Columbia University - Department of Medicine ( email )

630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Medini K. Annavajhala

Columbia University - Department of Medicine ( email )

United States

Rajesh Kumar Soni

Columbia University - Proteomics and Macromolecular Crystallography Shared Resource ( email )

New York, NY 10032
United States

Tania Wong Fok Lung

Columbia University - Department of Pediatrics ( email )

NY
United States

Casey E. Hofstaedter

University of Maryland – Baltimore - Department of Microbial Pathogenesis ( email )

College Park
College Park, MD 20742
United States

Shivang Shah

Columbia University - Department of Pediatrics

NY
United States

Alexander M. Chong

Columbia University - Department of Medicine ( email )

630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Victor G. Castano

Columbia University - Department of Pediatrics

NY
United States

Robert K. Ernst

University of Maryland – Baltimore - Department of Microbial Pathogenesis

College Park
College Park, MD 20742
United States

Anne-Catrin Uhlemann

Columbia University - Department of Medicine

United States

Alice Prince

Columbia University - Department of Pediatrics

630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

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