An acquired acyltransferase promotes Klebsiella pneumoniae ST258 respiratory infection.

Abstract

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.

• Authors: 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
• Journal: Cell reports (Cell Rep) Vol. 35 Issue 9 Pg. 109196 (06 01 2021) ISSN: 2211-1247 [Electronic] United States
• PMID: 34077733 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Proteins
• Carbapenems
• Lipid A
• Acyltransferases
• Glucose
• Lysine

Topics

• Acetylation
• Acyltransferases (metabolism)
• Animals
• Bacterial Proteins (genetics, metabolism)
• Carbapenems (pharmacology)
• Citric Acid Cycle
• Gene Deletion
• Glucose (metabolism)
• Glycolysis (drug effects)
• Klebsiella Infections (enzymology, microbiology)
• Klebsiella pneumoniae (enzymology, growth & development, isolation & purification, physiology)
• Lipid A (metabolism)
• Lung (drug effects, microbiology, pathology)
• Lysine (metabolism)
• Male
• Metabolome (drug effects)
• Metabolomics
• Mice, Inbred C57BL
• Phylogeny
• Protein Processing, Post-Translational (drug effects)
• Respiratory Tract Infections (enzymology, microbiology)