Molecular Analysis of a Leprosy Immunotherapeutic Bacillus Provides Insights into Mycobacterium Evolution
Molecular Analysis of a Leprosy Immunotherapeutic Bacillus Provides Insights into Mycobacterium Evolution
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DOI：
10.1371/journal.pone.0000968
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发表时间：
2007-10-03
期刊：
影响因子：
3.7
通讯作者：
Hasnain, Seyed E.
中科院分区：
文献类型：
--
作者：
Ahmed, Niyaz;Saini, Vikram;Hasnain, Seyed E.
背景进化动力学在促进致病性和致病性分枝杆菌之间的物种分化机制中起着核心作用。分枝杆菌定殖宿主、增殖和引起疾病的能力由于其在一段时间内对各种进化力量的易感性而进化。pranii分枝杆菌（Mycobacterium indicus pranii，MIP）是一种分类学上未知的“多面手”分枝杆菌，作为麻风病的免疫抑制剂，已被批准用于麻风病疫苗的研制。MIP，市售的“Immuvac”，目前是先进的III期临床试验的重点，其抗结核病的疗效。因此，最迫切需要的是对MIP的进化路径进行全面分析，以支持其不可或缺的免疫调节特性。主要发现。通过荧光扩增片段长度多态性（FAFLP）、肠杆菌重复基因间一致性（ERIC）基因分型和候选直向同源物测序进行的全基因组比较和分子系统发育分析显示，MIP是高致病性鸟胞内分枝杆菌复合体（MAIC）的前身，该复合体不依赖于通过还原基因进化的寄生适应，因此更喜欢自由生活的生活方式。进一步的分析表明，MAIC杆菌与分枝杆菌的早期致病形式共享水相，早在后者分化为“专家”之前。结论/意义。这种进化范式可能肯定了我们对分枝杆菌毒力的获得和优化及其边界决定因素的理解。
Background. Evolutionary dynamics plays a central role in facilitating the mechanisms of species divergence among pathogenic and saprophytic mycobacteria. The ability of mycobacteria to colonize hosts, to proliferate and to cause diseases has evolved due to its predisposition to various evolutionary forces acting over a period of time. Mycobacterium indicus pranii (MIP), a taxonomically unknown 'generalist' mycobacterium, acts as an immunotherapeutic against leprosy and is approved for use as a vaccine against it. The large-scale field trials of this MIP based leprosy vaccine coupled with its demonstrated immunomodulatory and adjuvant property has led to human clinical evaluations of MIP in interventions against HIV-AIDS, psoriasis and bladder cancer. MIP, commercially available as 'Immuvac', is currently the focus of advanced phase III clinical trials for its antituberculosis efficacy. Thus a comprehensive analysis of MIP vis-a-vis evolutionary path, underpinning its immanent immunomodulating properties is of the highest desiderata. Principal Findings. Genome wide comparisons together with molecular phylogenetic analyses by fluorescent amplified fragment length polymorphism (FAFLP), enterobacterial repetitive intergenic consensus (ERIC) based genotyping and candidate orthologues sequencing revealed that MIP has been the predecessor of highly pathogenic Mycobacterium avium intracellulare complex (MAIC) that did not resort to parasitic adaptation by reductional gene evolution and therefore, preferred a free living life-style. Further analysis suggested a shared aquatic phase of MAIC bacilli with the early pathogenic forms of Mycobacterium, well before the latter diverged as 'specialists'. Conclusions/Significance. This evolutionary paradigm possibly affirms to marshal our understanding about the acquisition and optimization of virulence in mycobacteria and determinants of boundaries therein.