Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles

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 emer...

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Autores principales:	Tomoya Maeda, Masako Kawada, Natsue Sakata, Hazuki Kotani, Chikara Furusawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1381d8003334066b3d08f735c1b3eda
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spelling	oai:doaj.org-article:e1381d8003334066b3d08f735c1b3eda2021-12-02T17:57:16ZLaboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles10.1038/s41598-021-94645-z2045-2322https://doaj.org/article/e1381d8003334066b3d08f735c1b3eda2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94645-zhttps://doaj.org/toc/2045-2322Abstract 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.Tomoya MaedaMasako KawadaNatsue SakataHazuki KotaniChikara FurusawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomoya Maeda Masako Kawada Natsue Sakata Hazuki Kotani Chikara Furusawa Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
description	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.
format	article
author	Tomoya Maeda Masako Kawada Natsue Sakata Hazuki Kotani Chikara Furusawa
author_facet	Tomoya Maeda Masako Kawada Natsue Sakata Hazuki Kotani Chikara Furusawa
author_sort	Tomoya Maeda
title	Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
title_short	Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
title_full	Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
title_fullStr	Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
title_full_unstemmed	Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
title_sort	laboratory evolution of mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e1381d8003334066b3d08f735c1b3eda
work_keys_str_mv	AT tomoyamaeda laboratoryevolutionofmycobacteriumonagarplatesforanalysisofresistanceacquisitionanddrugsensitivityprofiles AT masakokawada laboratoryevolutionofmycobacteriumonagarplatesforanalysisofresistanceacquisitionanddrugsensitivityprofiles AT natsuesakata laboratoryevolutionofmycobacteriumonagarplatesforanalysisofresistanceacquisitionanddrugsensitivityprofiles AT hazukikotani laboratoryevolutionofmycobacteriumonagarplatesforanalysisofresistanceacquisitionanddrugsensitivityprofiles AT chikarafurusawa laboratoryevolutionofmycobacteriumonagarplatesforanalysisofresistanceacquisitionanddrugsensitivityprofiles
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Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles

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