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

Abstract

The pathogenic Gram-positive bacterium Listeria monocytogenes has been evolving into a few phylogenetic lineages. Phylogenetically defined substitutions were described in the L. monocytogenes virulence factor InlB, which mediates active invasion into mammalian cells via interactions with surface receptors c-Met and gC1q-R. InlB internalin domain (idInlB) is central to interactions with c-Met. Here we compared activity of purified recombinant idInlB isoforms characteristic for L. monocytogenes phylogenetic lineage I and II. Size exclusion chromatography and intrinsic fluorescence were used to characterize idInlBs. Western blotting was used to study activation of c-Met-dependent MAPK- and PI3K/Akt-pathways. Solid-phase microplate binding and competition assay was used to quantify interactions with gCq1-R. Isogenic recombinant L. monocytogenes strains were used to elucidate the input of idInlB isoforms in HEp-2 cell invasion. Physicochemical parameters of idInlB isoforms were similar but not identical. Kinetics of Erk1/2 and Akt phosphorylation in response to purified idInlBs was lineage specific. Lineage I but not lineage II idInlB specifically bound gC1q-R. Antibody against gC1q-R amino acids 221–249 inhibited invasion of L. monocytogenes carrying lineage I but not lineage II idInlB. Taken together, obtained results suggested that phylogenetically defined substitutions in idInlB provide functional distinctions and might be involved in phylogenetically determined differences in virulence potential.

Genomic Characterization of Listeria monocytogenes Isolated From Ready-to-Eat Meat and Meat Processing Environments in Poland

“…Strains with the same deletion, isolated from mushroom production environment, have been identified previously (Muruesan et al, 2015). It has been described that different isoforms of the inlB gene have an impact on signaling pathways and invasiveness of L. monocytogenes (Wałecka-Zacharska et al, 2015;Sobyanin et al, 2017;Chalenko et al, 2019). Of note, differences in the sequences of the inlB gene among strains of wild animals and humans were observed, which may suggest that mutations in this gene may have an impact on the invasiveness of L. monocytogenes (Zaytseva et al, 2007).…”

Listeriolysin O Pore-Forming Activity Is Required for ERK1/2 Phosphorylation During Listeria monocytogenes Infection

“…These pathogens often use effector proteins to manipulate MAPK pathways and allow the bacteria to establish infection within the host (21). Employing a model of the bloodcerebrospinal fluid barrier based on human choroid plexus epithelial papilloma (HIBCPP) cells, a previous study showed that infection with L. monocytogenes triggers activation of ERK1/2 and p38 signaling, and such cellular response is required for L. monocytogenes infection (22,25). Modulation of MAPK pathway signaling by LLO during L. monocytogenes infection has been described in various host cell lines.…”

Listeria monocytogenes Infection of Bat Pipistrellus nathusii Epithelial cells Depends on the Invasion Factors InlA and InlB

“…The host receptor of InlA is the epithelial cell receptor E-cadherin [ 43 ]. InlB interacts with the tyrosine kinase c-Met and with the complement system receptor gC1q-R [ 44 , 45 , 46 ]. Interactions between InlA and E-cadherin are of key importance for the efficient crossing of the intestinal barrier [ 47 ].…”