Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope.
Acinetobacter Infections
/ drug therapy
Acinetobacter baumannii
/ drug effects
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ antagonists & inhibitors
Cell Wall
/ drug effects
Cross Infection
/ drug therapy
DNA Mutational Analysis
DNA Transposable Elements
/ genetics
DNA, Bacterial
/ genetics
Drug Resistance, Multiple, Bacterial
/ drug effects
Drug Synergism
Humans
Microbial Sensitivity Tests
Mutation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 09 2020
09 09 2020
Historique:
received:
02
03
2020
accepted:
13
08
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
2
10
2020
Statut:
epublish
Résumé
A unique, protective cell envelope contributes to the broad drug resistance of the nosocomial pathogen Acinetobacter baumannii. Here we use transposon insertion sequencing to identify A. baumannii mutants displaying altered susceptibility to a panel of diverse antibiotics. By examining mutants with antibiotic susceptibility profiles that parallel mutations in characterized genes, we infer the function of multiple uncharacterized envelope proteins, some of which have roles in cell division or cell elongation. Remarkably, mutations affecting a predicted cell wall hydrolase lead to alterations in lipooligosaccharide synthesis. In addition, the analysis of altered susceptibility signatures and antibiotic-induced morphology patterns allows us to predict drug synergies; for example, certain beta-lactams appear to work cooperatively due to their preferential targeting of specific cell wall assembly machineries. Our results indicate that the pathogen may be effectively inhibited by the combined targeting of multiple pathways critical for envelope growth.
Identifiants
pubmed: 32908144
doi: 10.1038/s41467-020-18301-2
pii: 10.1038/s41467-020-18301-2
pmc: PMC7481262
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
DNA Transposable Elements
0
DNA, Bacterial
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4522Commentaires et corrections
Type : ErratumIn
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