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Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
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| Title: | Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles |
| Authors: | Maeda, Tomoya Browse this author →KAKEN DB | | Kawada, Masako Browse this author | | Sakata, Natsue Browse this author | | Kotani, Hazuki Browse this author | | Furusawa, Chikara Browse this author |
| Issue Date: | 23-Jul-2021 |
| Publisher: | Nature Portfolio |
| Journal Title: | Scientific reports |
| Volume: | 11 |
| Issue: | 1 |
| Start Page: | 15136 |
| Publisher DOI: | 10.1038/s41598-021-94645-z |
| 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. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82659 |
| Appears in Collections: | 農学院・農学研究院 (Graduate School of Agriculture / Faculty of Agriculture) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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