Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope
| Autor: | Nadav J. Mortman, Amy Y. Tang, Murat Cokol, Sapna Syal, Jon Anthony, Stephen Wood, Tim van Opijnen, Ralph R. Isberg, Delaney G. Fisher, Yunfei Dai, Andrew Farinha, Edward Geisinger, David W. Lazinski |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-18301-2 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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