Beyond Paralogs: The Multiple Layers of Redundancy in Bacterial Pathogenesis.
Beyond Paralogs: The Multiple Layers of Redundancy in Bacterial Pathogenesis.
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DOI：
10.3389/fcimb.2017.00467
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发表时间：
2017
影响因子：
5.7
通讯作者：
O'Connor TJ
中科院分区：
文献类型：
--
作者：
Ghosh S;O'Connor TJ
冗余被称为不再需要或有用的状态。微生物学家通常认为，在单倍体生物体中，唯一真正冗余的情况是最近的基因复制事件，在通过选择压力产生分歧之前。然而，越来越多的例子存在，其中一个生物体编码两个基因，似乎执行相同的功能。例如，许多病原体将多种效应蛋白易位到宿主中。虽然单个效应基因的破坏不会导致可辨别的表型，但联合删除基因会损害发病机制：这被描述为冗余。在许多情况下，这种明显的冗余可能是由于实验室发病机制模型的局限性，不能完全概括疾病的过程。另一种可能是，这种感知到的冗余所获得的选择性优势太微妙，无法在实验室中测量。此外，不同类型的冗余有多种可能性。最常见和公认的冗余形式是功能冗余，即两种蛋白质具有相似的生化活性和底物特异性，允许每一种蛋白质在缺乏另一种蛋白质的情况下进行补偿。然而，冗余也可以存在于看似无关的蛋白质之间，这些蛋白质操纵相同或互补的宿主细胞途径。在这篇文章中，我们概述了5种类型的冗余发病机制：分子，靶，途径，细胞过程，系统冗余，包括生化活性，宿主靶特异性和效应功能的影响，他们调节的途径和细胞过程。对于每种类型的冗余，我们提供了军团菌发病机制的例子，因为这种生物体使用超过300种分泌的毒力蛋白，单个蛋白质的丢失很少影响细胞内生长。我们还讨论了驱动冗余机制维护的选择性压力，目前用于解决冗余的方法和区分冗余和非冗余毒力机制的功能。
Redundancy has been referred to as a state of no longer being needed or useful. Microbiologists often theorize that the only case of true redundancy in a haploid organism would be a recent gene duplication event, prior to divergence through selective pressure. However, a growing number of examples exist where an organism encodes two genes that appear to perform the same function. For example, many pathogens translocate multiple effector proteins into hosts. While disruption of individual effector genes does not result in a discernable phenotype, deleting genes in combination impairs pathogenesis: this has been described as redundancy. In many cases, this apparent redundancy could be due to limitations of laboratory models of pathogenesis that do not fully recapitulate the disease process. Alternatively, it is possible that the selective advantage achieved by this perceived redundancy is too subtle to be measured in the laboratory. Moreover, there are numerous possibilities for different types of redundancy. The most common and recognized form of redundancy is functional redundancy whereby two proteins have similar biochemical activities and substrate specificities allowing each one to compensate in the absence of the other. However, redundancy can also exist between seemingly unrelated proteins that manipulate the same or complementary host cell pathways. In this article, we outline 5 types of redundancy in pathogenesis: molecular, target, pathway, cellular process, and system redundancy that incorporate the biochemical activities, the host target specificities and the impact of effector function on the pathways and cellular process they modulate. For each type of redundancy, we provide examples from Legionella pathogenesis as this organism employs over 300 secreted virulence proteins and loss of individual proteins rarely impacts intracellular growth. We also discuss selective pressures that drive the maintenance of redundant mechanisms, the current methods used to resolve redundancy and features that distinguish between redundant and non-redundant virulence mechanisms.