Both TLR2 and TRIF Contribute to Interferon-β Production during Listeria Infection

Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression

Recruitment of the Major Vault Protein by InlK: A Listeria monocytogenes Strategy to Avoid Autophagy

L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK− bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

Cytosolic innate immune sensing and signaling upon infection

International audienceCytosolic sensing of pathogens is essential to a productive immune response. Recent reports have emphasized the importance of signaling platforms emanating from organelles and cytosolic sensors, particularly during the response to intracellular pathogens. Here, we highlight recent discoveries identifying the key mediators of nucleic acid and cyclic nucleotide sensing and discuss their importance in host defense. This review will also cover strategies evolved by pathogens to manipulate these pathways

Three decades of listeriology through the prism of technological advances

Decades of breakthroughs resulting from cross feeding of microbiological research and technological innovation have promoted Listeria monocytogenes to the rank of model microorganism to study host-pathogen interactions. The extraordinary capacity of this bacterium to interfere with a vast array of host cellular processes uncovered new concepts in microbiology, cell biology and infection biology. Here, we review technological advances that revealed how bacteria and host interact in space and time at the molecular, cellular, tissue and whole body scales, ultimately revolutionising our understanding of Listeria pathogenesis. With the current bloom of multidisciplinary integrative approaches, Listeria entered a new microbiology era

Raw data from Pacbio, assemblies and annotation of Xen31 and Xen36 strains

This deposit contains: raw pacbio data related to two samples of Staphylococcus aureus subsp. aureus MRSA252 (strains Xen31 and Xen36). assemblies in forms of fasta files annotations of the two main chromosomes The sequencing was performed on Pacbio Sequel on different so-called smartcells. Full details about library prepration, sequencing runs, etc can be found on array express under number E-MTAB-12210 (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-12210). Because there were two smartcells, there are two files per samples. The two files xen31_A.subreads.bam and xen31_B.subreads.bam are therefore the raw data of the strain Xen31. similarly the two files xen36_A.subreads.bam and xen36_B.subreads.bam are the raw data of the strain Xen36. These 2 files should be merged before analysis. Be aware that the data is not hifi data nor CCS (corrected). CCS files are provided on the array express link here above. Extra information about the quality assessments (in terms of coverage) of the assemblies can be found here : https://github.com/biomics-pasteur-fr/manuscript_B4410/edit/main/README.md and in a paper to be provided. In this deposit you can find the the four raw files named e.g. xen31_A.subreads.bam for the first smrtcell of strain 31 the results of the assemblies using Canu1.6 . In both strains a main contig corresponding to the entire S. aureus chromosome was obtained e.g. xen31_chromosome.fa Extra contigs are stored in xen31_other_contigs.fa annotations of the main chromosome were performed with prokka 1.14.5 and genbank and GFF format are provided here

Molecular determinants of Listeria monocytogenes virulence

International audienceListeria monocytogenes is the etiological agent of listeriosis, a severe human foodborne infection characterized by gastroenteritis, meningitis, encephalitis, abortions, and perinatal infections. This gram-positive bacterium is a facultative intracellular pathogen that induces its own uptake into nonphagocytic cells and spreads from cell to cell using an actin-based motility process. This review covers both well-established and recent advances in the characterization of L. monocytogenes virulence determinants and their role in the pathophysiology of listeriosis

The impact of growth history and flagellation on the adhesion of various Listeria monocytogenes strains to polystyrene

International audienceThe contribution of growth history and flagella to adhesion of Listeria monocytogenes was analysed. An in-frame deletion on the flagellin encoding gene (flaA) was performed in L. monocytogenes EGD-e to compare its adhesion ability with the parental strain, after cultivation at various pH values and temperatures. The pH, as well as the temperature, affected the adhesion of L. monocytogenes EGD-e. In addition, the adhesion of L. monocytogenes EGD-e was reduced in energy-depressed cells. Conversely, the physicochemical bacterial surface characteristics affected by growth history did not influence the adhesion. Adhesion variations observed among environmental and clinical strains was attributed to the flagella. The naturally aflagellated strains resulted in an adhesion capacity similar to that observed for mutants and parental strains cultivated under flagellum expression repressing conditions. However, L. monocytogenes is able to adhere to inert surfaces through a residual adhesion process without flagella. All these observations emphasize the importance to consider the food environmental factors in the risk assessment of L. monocytogenes in food industry.La contribution de l’historique de croissance et du flagelle dans l’adhérence de Listeria monocytogenes a été analysée. Une délétion en phase du gène codant la flagelline (flaA) a été réalisée chez L. monocytogenes EGD-e afin de comparer ses capacités d’adhérence à celles de la souche sauvage, après culture à différents pH et températures. Le pH et la température ont affecté l’adhérence de L. monocytogenes EGD-e. De plus, l’adhérence de L. monocytogenes EGD-e était réduite chez les cellules privées d’énergie. À l’inverse, les caractéristiques physicochimiques des éléments de surface bactériens affectés par l’historique de croissance n’influençaient pas l’adhérence. Les variations d’adhérence observées parmi les isolats environnementaux et cliniques ont été attribuées au flagelle. Les souches naturellement sans flagelle adhéraient de la même façon que les souches mutantes ou les souches sauvages cultivées sous des conditions de répression de l’expression du flagelle. Cependant, L. monocytogenes est capable d’adhérer à des surfaces inertes via un processus d’adhérence résiduel sans flagelle. Toutes ces observations soulignent l’importance de considérer les facteurs alimentaires environnementaux lors de l’évaluation du risque que constitue L. monocytegenes dans l’industrie alimentaire