An acquired acyltransferase promotes Klebsiella pneumoniae ST258 respiratory infection.
Acetylation
Acyltransferases
/ metabolism
Animals
Bacterial Proteins
/ genetics
Carbapenems
/ pharmacology
Citric Acid Cycle
Gene Deletion
Glucose
/ metabolism
Glycolysis
/ drug effects
Klebsiella Infections
/ enzymology
Klebsiella pneumoniae
/ enzymology
Lipid A
/ metabolism
Lung
/ drug effects
Lysine
/ metabolism
Male
Metabolome
/ drug effects
Metabolomics
Mice, Inbred C57BL
Phylogeny
Protein Processing, Post-Translational
/ drug effects
Respiratory Tract Infections
/ enzymology
Klebsiella pneumoniae
acetylation
bacterial pneumonia
glycolysis
metabolism
sequence type 258
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
18
11
2020
revised:
12
02
2021
accepted:
10
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
12
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34077733
pii: S2211-1247(21)00542-8
doi: 10.1016/j.celrep.2021.109196
pmc: PMC8283688
mid: NIHMS1710590
pii:
doi:
Substances chimiques
Bacterial Proteins
0
Carbapenems
0
Lipid A
0
Acyltransferases
EC 2.3.-
Glucose
IY9XDZ35W2
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
109196Subventions
Organisme : NIAID NIH HHS
ID : T32 AI100852
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL138289
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI146284
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135800
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123820
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116939
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI147314
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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