Route of Injection Affects the Impact of InlB Internalin Domain Variants on Severity ofListeria monocytogenesInfection in Mice

Abstract

The facultative intracellular pathogen Listeria monocytogenes causes a severe food-borne infection in humans and animals. L. monocytogenes invasion factor InlB interacts with the tyrosine kinase c-Met via the N-terminal internalin domain. Previously, distinct variants of the InlB internalin domain (idInlB) have been described in L. monocytogenes field isolates. Three variants were used to restore full-length InlB expression in the L. monocytogenes strain EGDeΔinlB. Obtained isogenic L. monocytogenes strains were tested in the invasion assay and intravenous, intraperitoneal, and intragastric models of infection in mice. All idInlBs were functional, restored InlB activity as an invasion factor, and improved invasion of the parental strain EGDeΔinlB into human kidney HEK23 cells. Meanwhile, distinct idInlBs provided different mortality rates and bacterial loads in internal organs. When recombinant strains were compared, the variant designated idInlB14 decreased severity of disease caused by intravenous and intraperitoneal bacterial administration, whereas this variant improved intestine colonization and stimulated intragastric infection. Obtained results demonstrated that naturally occurring idInlBs differed in their impact on severity of L. monocytogenes infection in mice in dependence on the infection route.

Phylogenetically Defined Isoforms of Listeria monocytogenes Invasion Factor InlB Differently Activate Intracellular Signaling Pathways and Interact with the Receptor gC1q-R

“…Overall, obtained results demonstrated differences in functional activities of phylogenetically defined idInlB isoforms. These differences are in line with previously obtained data that demonstrated that isogenic recombinant L. monocytogenes strains expressing full length InlB variants differed by idInlB only have different virulence for mice [36]. Taken together, these observations suggested that idInlB isoforms might provide different effects on L. monocytogenes virulence, that in turn might be one of foundations of the different virulence potential of L. monocytogenes phylogenetic lineages and/or distinct clonal groups.…”

“…Two lineage II forms were taken because the variant idInlB13 from the type strain EGDe is the best described and used in a number of studies [45,53] while idInlB14 is the most frequent among serovar 1/2a L. monocytogenes strains isolated from wild animals, clinical samples and other sources [33,34,54]. Moreover, a difference in their impact on virulence has been shown previously [35,36,55]. Amino acid substitutions which differentiate the variants are shown in the Figure 1a.…”

“…This isoform designated as idInlB14 was described in strains belonging to clonal complexes CC7, CC8, CC14, CC19, CC20, and some others [33,34]. Being placed in the same genetic background, InlB isoforms differently affected L. monocytogenes virulence in mice [35,36]. These data suggest that natural InlB isoforms could have some differences in their functionality.…”

Retrospective Study of Listeria Monocytogenes Isolated in the Territory of Inner Eurasia from 1947 to 1999

“…This prevalence might be due to some selective advantage of this allele. Recently, we demonstrated that inlB allele 14 provided the highest level of L. monocytogenes dissemination to the internal organs of mice when infection was performed via intragastric inoculation, which is the best model of the natural infection process [58]. All lineage II strains isolated from internal mouse organs in this and previous studies carried the inlB allele 14, and mice might be an important host for L. monocytogenes in the natural focus of infection [38].…”

Relative Roles of Listeriolysin O, InlA, and InlB in Listeria monocytogenes Uptake by Host Cells

“…Of the three factors, LLO is the most important for virulence, as LLO-deficient strains are avirulent, so dissecting its role in vivo is challenging. In mice infected with 10403S or EGD-e, InlB does not affect liver and spleen colonization or the 50% lethal dose (LD 50 ) ( 81 , 82 ). One recent study infecting E-cadherin-humanized mice and gerbils with EGD ( prfA* ) showed that neither InlA nor InlB affected infection of the liver ( 7 ).…”