From ancestor to pathogen: Expansion and evolutionary adaptations of multidrug resistance causing MFS efflux pumps in mycobacteria.

IF 2.6 3区 生物学 Q2 GENETICS & HEREDITY Gene Pub Date : 2024-12-12 DOI:10.1016/j.gene.2024.149160
Garima Singh, Yusuf Akhter
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引用次数: 0

Abstract

Multidrug resistance (MDR) in Mycobacterium tuberculosis (Mtb) is a growing threat. Efflux pumps, particularly those belonging to the Major Facilitator Superfamily (MFS), play a key role in MDR. This study investigated MFS transporters across Mycobacterium spp. to understand their evolution and role in drug resistance. We conducted a proteome-wide analysis of MFS proteins in Mtb, Mycobacterium smegmatis (non-pathogenic), and Mycobacterium canettii (closely related ancestor of Mtb). Mtb, known for its MDR, possessed the highest abundance of MFS drug efflux pumps, while Mycobacterium smegmatis had the least. This suggests a link between MFS drug efflux pump abundance and MDR phenotypes. Interestingly, Mycobacterium canettii displayed an intermediate level, possibly indicating the presence of these pumps before the emergence of Mtb as a pathogen. Further analysis of Mtb proteome revealed 31 putative MFS transporters and 3 proteins from expanded MFS subfamilies. Phylogenetic analysis categorized them into thirteen distinct families based on structural features. These findings highlight the potential importance of MFS transporters in MDR and the pathogenicity of Mtb. Overall, this study highlights the evolutionary role of MFS transporters in bacterial adaptation to antibiotics. The observed correlation between efflux pump abundance and MDR suggests MFS transporters as promising targets for future anti-tuberculosis therapies. Further research on specific transporter functions within MFS subfamilies can pave the way for novel therapeutic strategies.

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从祖先到病原体:分枝杆菌中引起多药耐药性的 MFS 外排泵的扩展和进化适应。
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来源期刊
Gene
Gene 生物-遗传学
CiteScore
6.10
自引率
2.90%
发文量
718
审稿时长
42 days
期刊介绍: Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.
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