The Bioinformatics Analysis of Comparative Genomics of Mycobacterium tuberculosis Complex (MTBC) Provides Insight into Dissimilarities between Intraspecific Groups Differing in Host Association, Virulence, and Epitope Diversity.
The Bioinformatics Analysis of Comparative Genomics of Mycobacterium tuberculosis Complex (MTBC) Provides Insight into Dissimilarities between Intraspecific Groups Differing in Host Association, Virulence, and Epitope Diversity.
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结核分枝杆菌复合体 (MTBC) 比较基因组学的生物信息学分析可深入了解不同宿主关联、毒力和表位多样性的种内群体之间的差异
DOI：
10.3389/fcimb.2017.00088
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发表时间：
2017
影响因子：
5.7
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Jia X;Yang L;Dong M;Chen S;Lv L;Cao D;Fu J;Yang T;Zhang J;Zhang X;Shang Y;Wang G;Sheng Y;Huang H;Chen F
结核病现在超过艾滋病毒，成为导致死亡的头号传染病，由结核分枝杆菌复合体（MTBC）引起。MTBC菌株具有高度保守的基因组序列（相似性>99%），但具有显著不同的表型。为了分析基因型和表型之间的关系，我们对代表不同谱系的12个MTBC菌株进行了比较基因组分析（即，牛分枝杆菌; M. bovis BCG; M. microti; M. africanum; M.结核分枝杆菌H37 Rv;结核菌H37 Ra和6株M.结核病临床分离株）。分析的重点是三个方面的致病性：宿主协会，毒力，表位变异。宿主关联分析表明，8个mce 3基因，两个烯酰辅酶A水合酶，和5个PE/PPE家族基因只存在于人类分离株，这些可能有作用，在宿主-病原体相互作用。在毒力因子上发现15个SNPs（其中3个ESX分泌蛋白中有5个SNPs），仅在北京株中发现，这可能与北京株毒力更强的表型有关。强毒H37 Rv和非强毒H37 Ra菌株之间的比较揭示了可能与H37 Ra的毒力减毒相关的三个SNP：S219 L（PhoP）、A219 E（MazG）和新鉴定的I228 M（EspK）。此外，动物相关MTBC菌株的比较显示，前四个基因（即，pe 35，pe 68，esxB，esxA），而不是RD 1的所有8个基因，可能在动物分离株的毒力衰减中起核心作用。最后，通过比较MTBC菌株之间的表位，我们发现只有北京菌株丢失了四个表位;这可能使它们能够更好地逃避人类免疫系统，从而增强毒力。总的来说，我们的MTBC菌株的比较基因组分析揭示了高度保守的基因型和MTBC的不同表型之间的关系，提供了深入了解致病机制，并促进了预防和治疗结核病的潜在分子靶点的发展。
Tuberculosis now exceeds HIV as the top infectious disease cause of mortality, and is caused by the Mycobacterium tuberculosis complex (MTBC). MTBC strains have highly conserved genome sequences (similarity >99%) but dramatically different phenotypes. To analyze the relationship between genotype and phenotype, we conducted the comparative genomic analysis on 12 MTBC strains representing different lineages (i.e., Mycobacterium bovis; M. bovis BCG; M. microti; M. africanum; M. tuberculosis H37Rv; M. tuberculosis H37Ra, and six M. tuberculosis clinical isolates). The analysis focused on the three aspects of pathogenicity: host association, virulence, and epitope variations. Host association analysis indicated that eight mce3 genes, two enoyl-CoA hydratases, and five PE/PPE family genes were present only in human isolates; these may have roles in host-pathogen interactions. There were 15 SNPs found on virulence factors (including five SNPs in three ESX secretion proteins) only in the Beijing strains, which might be related to their more virulent phenotype. A comparison between the virulent H37Rv and non-virulent H37Ra strains revealed three SNPs that were likely associated with the virulence attenuation of H37Ra: S219L (PhoP), A219E (MazG) and a newly identified I228M (EspK). Additionally, a comparison of animal-associated MTBC strains showed that the deletion of the first four genes (i.e., pe35, ppe68, esxB, esxA), rather than all eight genes of RD1, might play a central role in the virulence attenuation of animal isolates. Finally, by comparing epitopes among MTBC strains, we found that four epitopes were lost only in the Beijing strains; this may render them better capable of evading the human immune system, leading to enhanced virulence. Overall, our comparative genomic analysis of MTBC strains reveals the relationship between the highly conserved genotypes and the diverse phenotypes of MTBC, provides insight into pathogenic mechanisms, and facilitates the development of potential molecular targets for the prevention and treatment of tuberculosis.