Novel internalin P homologs in Listeria

Abstract

Listeria monocytogenes (Lm) is a bacterial pathogen that causes listeriosis in immunocompromised individuals, particularly pregnant women. Several virulence factors support the intracellular lifecycle of Lm 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 Lm 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 Lm to bind host proteins. Notably, other Listeria species express internalins but cannot colonize human hosts, prompting questions regarding the evolution of internalins within the genus Listeria . 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 Lm pathogenesis, there remains a lack of information regarding homologs in other Listeria species. Here, we have used a computational evolutionary approach to identify InlP homologs in additional Listeria species. We found that Listeria ivanovii londoniensis (Liv) and Listeria seeligeri (Ls) encode InlP homologs. We also found InlP-like homologs in Listeria innocua and the recently identified species Listeria costaricensis . All newly identified homologs lack the full-length LRR6 and LRR7 domains found in Lm’s InlP. These findings are informative regarding the evolution of one key Lm virulence factor, InlP, and serve as a springboard for future evolutionary studies of Lm pathogenesis as well as mechanistic studies of Listeria internalins.

MolEvolvR: A web-app for characterizing proteins using molecular evolution and phylogeny

“…Identifying and characterizing the complete molecular systems involved in such processes requires functional knowledge of the proteins involved. Many studies [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] have demonstrated the power of phylogenetic and molecular evolutionary analysis in determining the molecular functions of such proteins. A variety of individual tools exist for protein sequence similarity searches or ortholog detection, delineating co-occurring domains (domain architectures), and building multiple sequence alignments and phylogenetic trees.…”

“…MolEvolvR is a generalized web server of this web-app. To demonstrate its broad applicability, we have applied the approach underlying MolEvolvR to study several systems, including proteins/operons in zoonotic pathogens, e.g., nutrient acquisition systems in Staphylococcus aureus 4,5 , novel phage defense system in Vibrio cholerae 6 , surface layer proteins in Bacillus anthracis 7 , helicase operators in bacteria 8 , and internalins in Listeria spp 9 . We have included a few pre-loaded examples in MolEvolvR for users to explore in addition to help pages and FAQ.…”