論文 - 詳細
| RRC ID | 71384 |
|---|---|
| 著者 | Maeda T, Kawada M, Sakata N, Kotani H, Furusawa C. |
| タイトル | Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles. |
| ジャーナル | Sci Rep |
| Abstract |
Drug-resistant tuberculosis (TB) is a growing public health problem. There is an urgent need for information regarding cross-resistance and collateral sensitivity relationships among drugs and the genetic determinants of anti-TB drug resistance for developing strategies to suppress the emergence of drug-resistant pathogens. To identify mutations that confer resistance to anti-TB drugs in Mycobacterium species, we performed the laboratory evolution of nonpathogenic Mycobacterium smegmatis, which is closely related to Mycobacterium tuberculosis, against ten anti-TB drugs. Next, we performed whole-genome sequencing and quantified the resistance profiles of each drug-resistant strain against 24 drugs. We identified the genes with novel meropenem (MP) and linezolid (LZD) resistance-conferring mutation, which also have orthologs, in M. tuberculosis H37Rv. Among the 240 possible drug combinations, we identified 24 pairs that confer cross-resistance and 18 pairs that confer collateral sensitivity. The acquisition of bedaquiline or linezolid resistance resulted in collateral sensitivity to several drugs, while the acquisition of MP resistance led to multidrug resistance. The MP-evolved strains showed cross-resistance to rifampicin and clarithromycin owing to the acquisition of a mutation in the intergenic region of the Rv2864c ortholog, which encodes a penicillin-binding protein, at an early stage. These results provide a new insight to tackle drug-resistant TB. |
| 巻・号 | 11(1) |
| ページ | 15136 |
| 公開日 | 2021-7-23 |
| DOI | 10.1038/s41598-021-94645-z |
| PII | 10.1038/s41598-021-94645-z |
| PMID | 34302035 |
| PMC | PMC8302736 |
| MeSH | Agar / metabolism* Antitubercular Agents / pharmacology* Drug Resistance, Multiple, Bacterial / drug effects* Drug Resistance, Multiple, Bacterial / genetics Laboratories Microbial Sensitivity Tests / methods Mutation / genetics Mycobacterium smegmatis / drug effects* Mycobacterium smegmatis / genetics Mycobacterium tuberculosis / drug effects* Mycobacterium tuberculosis / genetics Whole Genome Sequencing / methods |
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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 | 2 |
| 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 | |
| 一般微生物 | JCM6386 |