論文 - 詳細
| RRC ID | 53739 |
|---|---|
| 著者 | Shuster Y, Steiner-Mordoch S, Alon Cudkowicz N, Schuldiner S. |
| タイトル | A Transporter Interactome Is Essential for the Acquisition of Antimicrobial Resistance to Antibiotics. |
| ジャーナル | PLoS One |
| Abstract |
Awareness of the problem of antimicrobial resistance (AMR) has escalated and drug-resistant infections are named among the most urgent problems facing clinicians today. Our experiments here identify a transporter interactome and portray its essential function in acquisition of antimicrobial resistance. By exposing E. coli cells to consecutive increasing concentrations of the fluoroquinolone norfloxacin we generated in the laboratory highly resistant strains that carry multiple mutations, most of them identical to those identified in clinical isolates. With this experimental paradigm, we show that the MDTs function in a coordinated mode to provide an essential first-line defense mechanism, preventing the drug reaching lethal concentrations, until a number of stable efficient alterations occur that allow survival. Single-component efflux transporters remove the toxic compounds from the cytoplasm to the periplasmic space where TolC-dependent transporters expel them from the cell. We postulate a close interaction between the two types of transporters to prevent rapid leak of the hydrophobic substrates back into the cell. The findings change the prevalent concept that in Gram-negative bacteria a single multidrug transporter, AcrAB-TolC type, is responsible for the resistance. The concept of a functional interactome, the process of identification of its members, the elucidation of the nature of the interactions and its role in cell physiology will change the existing paradigms in the field. We anticipate that our work will have an impact on the present strategy searching for inhibitors of AcrAB-TolC as adjuvants of existing antibiotics and provide novel targets for this urgent undertaking. |
| 巻・号 | 11(4) |
| ページ | e0152917 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0152917 |
| PII | PONE-D-16-04345 |
| PMID | 27050393 |
| PMC | PMC4822809 |
| MeSH | Carrier Proteins / metabolism* Culture Media Drug Resistance, Microbial* Escherichia coli / drug effects* Escherichia coli / metabolism Escherichia coli Proteins / metabolism* |
| IF | 2.74 |
| 引用数 | 10 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | |