Analysis of the contribution of MTP and the predicted Flp pilus genes to Mycobacterium tuberculosis pathogenesis.
Analysis of the contribution of MTP and the predicted Flp pilus genes to Mycobacterium tuberculosis pathogenesis.
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DOI：
10.1099/mic.0.000368
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发表时间：
2016-10
期刊：
影响因子：
1.5
通讯作者：
Katherine M Mann;A. C. Pride;Kelly N. Flentie;Jacqueline M. Kimmey;Leslie A. Weiss;Christina L. Stallings
中科院分区：
文献类型：
--
作者：
Katherine M Mann;A. C. Pride;Kelly N. Flentie;Jacqueline M. Kimmey;Leslie A. Weiss;Christina L. Stallings
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是世界上最成功的病原体之一。每年有数百万新的肺结核病例，这突出表明需要更好的治疗方法。新疗法的设计取决于我们对发病机制所必需的因素的理解。许多细菌病原体利用皮利和其他粘附素介导致病。最近鉴定的结核分枝杆菌菌毛（MTP）和假设的，广泛保守的Flp菌毛已被推测是重要的Mtb毒力的基础上，在体外研究和同源性，以其他皮利，分别。然而，这些皮利在感染过程中的作用还有待检验。我们解决了这方面的知识差距，发现MTP和假设的Flp菌毛都不是Mtb在小鼠感染模型中存活所必需的，尽管MTP可以促进生物膜形成和随后的异烟肼耐受性。然而，mtp表达的差异确实影响了感染肺的病变结构。缺失的MTP没有相关的细胞相关的细胞外结构的损失，如通过透射电子显微镜在结核病Erdman和HN 878株，这表明MTP突变体的表型是不是由于生产的细胞外结构的缺陷。这些发现强调了在动物模型中测试粘附突变体的毒力以评估粘附素对感染的贡献的重要性。这项研究还强调了需要进一步调查Mtb可能用于粘附其宿主的其他策略，以便我们可以了解这种病原体如何入侵，定植和传播。
Mycobacterium tuberculosis (Mtb) is one of the world's most successful pathogens. Millions of new cases of tuberculosis occur each year, emphasizing the need for better methods of treatment. The design of novel therapeutics is dependent on our understanding of factors that are essential for pathogenesis. Many bacterial pathogens use pili and other adhesins to mediate pathogenesis. The recently identified Mycobacterium tuberculosis pilus (MTP) and the hypothetical, widely conserved Flp pilus have been speculated to be important for Mtb virulence based on in vitro studies and homology to other pili, respectively. However, the roles for these pili during infection have yet to be tested. We addressed this gap in knowledge and found that neither MTP nor the hypothetical Flp pilus is required for Mtb survival in mouse models of infection, although MTP can contribute to biofilm formation and subsequent isoniazid tolerance. However, differences in mtp expression did affect lesion architecture in infected lungs. Deletion of mtp did not correlate with loss of cell-associated extracellular structures as visualized by transmission electron microscopy in Mtb Erdman and HN878 strains, suggesting that the phenotypes of the mtp mutants were not due to defects in production of extracellular structures. These findings highlight the importance of testing the virulence of adhesion mutants in animal models to assess the contribution of the adhesin to infection. This study also underscores the need for further investigation into additional strategies that Mtb may use to adhere to its host so that we may understand how this pathogen invades, colonizes and disseminates.