The Novel Internalins InlP1 and InlP4 and the Internalin-Like Protein InlP3 Enhance the Pathogenicity of Listeria monocytogenes

Abstract

The pathogenicity of the human foodborne pathogen Listeria monocytogenes relies on virulence factors such as internalins. In 2009/2010 two L. monocytogenes strains were responsible for a serious listeriosis outbreak in Austria, Germany, and the Czech Republic. One of these clones, QOC1, which caused 14 cases including five fatalities, encodes the novel internalins inlP1 , inlPq and inlP4 , and the novel internalin-like protein inlP3 in the genomic region of hypervariable genetic hotspot 9 in addition to the standard set of virulence genes. The in silico prevalence study revealed that these genes rarely occur in L. monocytogenes , mainly in minor clonal complexes. To obtain first insights of the role of these genes in the pathogenicity of L. monocytogenes , we studied the gene expression under conditions mimicking the ingestion in the host. Expression of inlP1 , inlP3 , inlPq and inlP4 was increased under gastric stress and in intracellular bacteria grown in intestinal epithelial cells. Furthermore, colonization of the liver and the spleen was slightly, but significantly reduced 72 h post infection in an oral mouse infection model when inlP1 or inlP4 was deleted. Moreover, the impact of InlP1 and InlP3 in virulence was shown in vitro in human intestinal epithelial cells. In this study we conclusively demonstrate a potential contribution of uncommon novel internalins and an internalin-like protein to the pathogenicity of L. monocytogenes .

Listeria monocytogenes Virulence, Antimicrobial Resistance and Environmental Persistence: A Review

“…Internalin K recruits a major vault protein (MVP) that camouflages the pathogen, shielding it from autophagic recognition [ 57 ]. Other novel internalins (InlP1, InlPq, and InlP4) which contribute to the virulence of L. monocytogenes , have been reported [ 58 ].…”

Potential Roles and Functions of Listerial Virulence Factors during Brain Entry

“…There are 25+ currently known Inl family members in Lm strain EGDe, which is the number most commonly quoted in reference to Inl family size [1,[24][25][26]. Other Inl or Inl-like proteins have been found in other strains and clinical isolates, however, and the number of newly described Inl family members continues to grow [26,27]. Two features common to the entire Inl family are a Sec-dependent N-terminal signal peptide and a leucine-rich repeat (LRR) domain [26].…”

Listeria monocytogenes infection in pregnant macaques alters the maternal gut microbiome

“…A study in mice found that listeriosis in aged mice enhanced the abundance of butyrate-producing inflammatory members of the Ruminococcaceae / Lachnospiraceae bacteria while beneficial commensals in the gut were reduced or eliminated entirely. Commensal species like Lactobacillus , Clostridiales , and Akkermansia were only abundant in infected young-adult mice, but their abundance diminished in the infected old mice [8]. These findings suggest that aging may affect the composition of gut microbiota and increase the risk of invasive Lm infection [57].…”

“…Bacterial surface proteins ActA and PrfA promote cell-to-cell spread, furthering infection and evading extracellular immune detection [37]. More recently characterized, InlP has been shown to interact with affadin to invade cells at the MFI [8][9][10]. Each of these virulence factors aid Lm in invasion, survival, and replication within the host cells.…”

“…Previous research has sought to understand the molecular mechanisms behind the pathogenic ability of Lm to infect the placenta, with a focus on factors such as internalins and host immune interactions [7][8][9][10]. However, few studies focus on the maternal gut microbiome during infection with a bacterial pathogen [11][12][13][14][15].…”