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Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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.<br />A unique cell envelope contributes to the antibiotic resistance of the pathogen Acinetobacter baumannii. Here, Geisinger et al. identify A. baumannii mutants with altered antibiotic susceptibility, infer the function of uncharacterized proteins involved in envelope synthesis, and predict antibiotic synergies.
- Subjects :
- 0301 basic medicine
Science
030106 microbiology
Mutant
General Physics and Astronomy
Drug resistance
DNA replication
Biology
medicine.disease_cause
Article
General Biochemistry, Genetics and Molecular Biology
Bacterial genetics
03 medical and health sciences
polycyclic compounds
medicine
Cellular microbiology
lcsh:Science
Pathogen
Gene
Genetics
Mutation
Multidisciplinary
Antimicrobials
General Chemistry
biochemical phenomena, metabolism, and nutrition
bacterial infections and mycoses
biology.organism_classification
Acinetobacter baumannii
030104 developmental biology
bacteria
lcsh:Q
Cell envelope
Microbial genetics
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....d77712b1778f56872fff5506de601f50