Portal de investigação
Heterogeneous Streptomycin Resistance Level Among Mycobacterium tuberculosis Strains From the Same Transmission Cluster
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Rocha, DMGC
- Magalhaes, C
- Cá, B
- Ramos, A
- Carvalho, T
- Comas, I
- Saraiva, M
- Osório, NS
Unidades de investigação
Abstract
Widespread and frequent resistance to the second-line tuberculosis (TB) medicine streptomycin, suggests ongoing transmission of low fitness cost streptomycin resistance mutations. To investigate this hypothesis, we studied a cohort of 681 individuals from a TB epidemic in Portugal. Whole-genome sequencing (WGS) analyses were combined with phenotypic growth studies in culture media and in mouse bone marrow derived macrophages. Streptomycin resistance was the most frequent resistance in the cohort accounting for 82.7% (n = 67) of the resistant Mycobacterium tuberculosis isolates. WGS of 149 clinical isolates identified 13 transmission clusters, including three clusters containing only streptomycin resistant isolates. The biggest cluster was formed by eight streptomycin resistant isolates with a maximum of five pairwise single nucleotide polymorphisms of difference. Interestingly, despite their genetic similarity, these isolates displayed different resistance levels to streptomycin, as measured both in culture media and in infected mouse bone marrow derived macrophages. The genetic bases underlying this phenotype are a combination of mutations in gid and other genes. This study suggests that specific streptomycin resistance mutations were transmitted in the cohort, with the resistant isolates evolving at the cluster level to allow low-to-high streptomycin resistance levels without a significative fitness cost. This is relevant not only to better understand transmission of streptomycin resistance in a clinical setting dominated by Lineage 4 M. tuberculosis infections, but mainly because it opens new prospects for the investigation of selection and spread of drug resistance in general.
Dados da publicação
- ISSN/ISSNe:
- 1664-302X, 1664-302X
- Tipo:
- Article
- Páginas:
- -
- Link para outro recurso:
- www.scopus.com
Frontiers in Microbiology Frontiers Media S.A.
Citações Recebidas na Web of Science: 9
Citações Recebidas na Scopus: 12
Documentos
- Não há documentos
Filiações
Keywords
- tuberculosis; streptomycin; resistance; transmission; evolution
Financiamento
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Citar a publicação
Rocha DMGC,Magalhaes C,Cá B,Ramos A,Carvalho T,Comas I,Guimaraes JT,Bastos HN,Saraiva M,Osório NS. Heterogeneous Streptomycin Resistance Level Among <i>Mycobacterium tuberculosis</i> Strains From the Same Transmission Cluster. Front. Microbiol. 2021. 12. 659545. IF:6,064. (1).
