Unlocking the Mycobacteroides abscessus pan-genome using computational tools: insights into evolutionary dynamics and lifestyle

Mistu Karmakar, Saubashya Sur
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Abstract

Mycobacteroides abscessus is a non-tuberculous mycobacteria implicated in causing lung infections. It is difficult to control owing to resistance to antibiotics and disinfectants. This work was aimed at comprehending: the pan-genome architecture, evolutionary dynamics, and functionalities of pan-genome components linked to COGs and KEGG. Around 2802 core genes were present in each strain of the M. abscessus genome. The number of accessory genes ranged from 1615 to 2481. The open pan-genome of M. abscessus was attributed to the accessory genes underlining its adaptability in the host. Phylogenetic analysis revealed cluster-based relationships and highlighted factors shaping variability and adaptive capabilities. Transcription, metabolism, and pathogenic genes were vital for M. abscessus lifestyle. The accessory genes contributed to the diverse metabolic capability. The incidence of a significant portion of secondary metabolite biosynthesis genes provided insights for investigating their biosynthetic gene clusters. Additionally, a high proportion of xenobiotic biodegradation genes highlighted potential metabolic capabilities. In silico screening identified a potential vaccine candidate among hypothetical proteins in COGs. Functional analysis of M. abscessus pan-genome components unveiled factors associated with virulence, pathogenicity, infection establishment, persistence, and resistance. Notable amongst them were: MMPL family transporters, PE-PPE domain-containing proteins, TetR family transcriptional regulators, ABC transporters, Type—I, II, III, VII secretion proteins, DUF domain-containing proteins, cytochrome P450, VapC family toxin, virulence factor Mce family protein, type II toxin-antitoxin system. Overall, these results enhanced understanding of the metabolism, host–pathogen dynamics, pathogenic lifestyle, and adaptations. This will facilitate further investigations for combating infections and designing suitable therapies.

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利用计算工具揭开脓肿分枝杆菌泛基因组的神秘面纱:洞察进化动态和生活方式
脓肿分枝杆菌是一种可引起肺部感染的非结核分枝杆菌。由于对抗生素和消毒剂具有抗药性,它很难受到控制。这项工作旨在了解:泛基因组结构、进化动态以及与 COGs 和 KEGG 相关联的泛基因组成分的功能。脓肿霉菌基因组的每个菌株中都有大约 2802 个核心基因。附属基因的数量从1615个到2481个不等。脓肿霉菌开放的泛基因组归因于附属基因,强调了其对宿主的适应性。系统发育分析揭示了基于聚类的关系,并强调了形成变异性和适应能力的因素。转录、代谢和致病基因对脓肿病菌的生活方式至关重要。附属基因对不同的代谢能力做出了贡献。大量次生代谢物生物合成基因的出现为研究其生物合成基因簇提供了启示。此外,高比例的异生物降解基因也凸显了潜在的代谢能力。硅学筛选在 COGs 中的假定蛋白中发现了一种潜在的候选疫苗。对脓肿病菌泛基因组成分的功能分析揭示了与毒力、致病性、感染建立、持续性和抵抗力有关的因素。其中值得注意的是MMPL家族转运体、含PE-PPE结构域的蛋白、TetR家族转录调节因子、ABC转运体、I型、II型、III型、VII型分泌蛋白、含DUF结构域的蛋白、细胞色素P450、VapC家族毒素、毒力因子Mce家族蛋白、II型毒素-抗毒素系统。总之,这些结果加深了人们对新陈代谢、宿主-病原体动态、致病生活方式和适应性的了解。这将有助于进一步研究抗感染和设计合适的疗法。
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来源期刊
CiteScore
5.60
自引率
11.50%
发文量
104
审稿时长
3 months
期刊介绍: Antonie van Leeuwenhoek publishes papers on fundamental and applied aspects of microbiology. Topics of particular interest include: taxonomy, structure & development; biochemistry & molecular biology; physiology & metabolic studies; genetics; ecological studies; especially molecular ecology; marine microbiology; medical microbiology; molecular biological aspects of microbial pathogenesis and bioinformatics.
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