Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA.
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
Microb Genom. 2022 Jul;8(7). doi: 10.1099/mgen.0.000828.
() is a bacterial pathogen that causes listeriosis in immunocompromised individuals, particularly pregnant women. Several virulence factors support the intracellular lifecycle of and facilitate cell-to-cell spread, allowing it to occupy multiple niches within the host and cross-protective barriers, including the placenta. One family of virulence factors, internalins, contributes to pathogenicity by inducing specific uptake and conferring tissue tropism. Over 25 internalins have been identified thus far, but only a few have been extensively studied. Internalins contain leucine-rich repeat (LRR) domains that enable protein-protein interactions, allowing to bind host proteins. Notably, other species express internalins but cannot colonize human hosts, prompting questions regarding the evolution of internalins within the genus . Internalin P (InlP) promotes placental colonization through interaction with the host protein afadin. Although prior studies of InlP have begun to elucidate its role in pathogenesis, there remains a lack of information regarding homologs in other species. Here, we have used a computational evolutionary approach to identify InlP homologs in additional species. We found that () and () encode InlP homologs. We also found InlP-like homologs in and the recently identified species . All newly identified homologs lack the full-length LRR6 and LRR7 domains found in 's InlP. These findings are informative regarding the evolution of one key virulence factor, InlP, and serve as a springboard for future evolutionary studies of pathogenesis as well as mechanistic studies of internalins.
李斯特菌是一种细菌病原体，会导致免疫功能低下的个体，特别是孕妇，患上李斯特菌病。一些毒力因子支持李斯特菌的细胞内生命周期，并促进细胞间传播，使它能够在宿主内占据多个小生境和跨越保护屏障，包括胎盘。一种毒力因子家族，内毒素，通过诱导特定的摄取并赋予组织趋向性来促进李斯特菌的致病性。迄今为止，已经鉴定出超过 25 种内毒素，但只有少数得到了广泛研究。内毒素含有富含亮氨酸重复（LRR）结构域，能够进行蛋白-蛋白相互作用，使李斯特菌能够与宿主蛋白结合。值得注意的是，其他李斯特菌物种也表达内毒素，但不能定植人类宿主，这引发了关于该属内内毒素进化的问题。肠内素 P（InlP）通过与宿主蛋白 afadin 相互作用促进胎盘定植。尽管先前对 InlP 的研究已经开始阐明其在李斯特菌发病机制中的作用，但其他李斯特菌物种中的同源物仍然缺乏信息。在这里，我们使用计算进化方法在其他李斯特菌物种中鉴定出 InlP 同源物。我们发现（）和（）编码 InlP 同源物。我们还在和最近鉴定的物种中发现了 InlP 样同源物。所有新鉴定的同源物都缺乏李斯特菌 InlP 中发现的全长 LRR6 和 LRR7 结构域。这些发现为李斯特菌一个关键毒力因子 InlP 的进化提供了信息，并为李斯特菌发病机制的未来进化研究以及内毒素的机制研究提供了跳板。
