P Cossart

..Their study may lead to a better understanding of important questions in cell biology such as ligand receptor signalling and dynamics of actin polymerization in mammalian cells...

..Together, Listeria, after being recognized as a powerful tool in immunology, now appears as one of the most insightful models in infection biology...

..Increasing evidence shows that many cellular genes are up- or down-regulated during infection and probably play a role in the establishment of infection, inflammation and induction of the host immune response...

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..The first identified ligand for InlB was gC1qR, which has no cytoplasmic domain. The newly discovered InlB receptor, Met, fits with the known InlB-induced signals...

..Our findings suggest that these latter proteins, which are known to play critical roles in cellular actin rearrangements, may also be involved in the dynamics of Listeria-induced actin assembly...

..They also shed light on a new function for clathrin in mammalian cells, i.e. internalization of objects much larger than previously accepted...

..The virulence gene cluster and its regulation by PrfA will be presented and discussed in the framework of the recently determined genome sequence...

..Manipulating the bacterial invasion proteins offers us an unprecedented tool with which to understand the complex phenomenon of phagocytosis...

..Orally acquired listeriosis can now be studied in relevant animal models. Finally, Listeria is among the few bacteria which have so rapidly benefited from comparative genomics. It now ranks among the most documented pathogens...

..The mechanisms underlying bacterial entry, phagosome maturation, and dissemination reveal common strategies as well as unique tactics evolved by individual species to establish infection...

..In this review we discuss several of the canonical host pathways targeted by bacterial pathogens and emerging areas of investigation in this exciting field...

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..Thus, FbpA, in addition to being a fibronectin-binding protein, behaves as a chaperone or an escort protein for two important virulence factors and appears as a novel multifunctional virulence factor of L. monocytogenes...

..Internalin is also detected in substantial amounts in culture supernatants. Taken together, these data suggest that surface-bound internalin plays an important role in bacterial entry but do not exclude a role for the released form...

..The identity of such an aspect remains to be determined...

..These results illustrate how relevant animal models for human infections can be generated...

..The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events...

..We propose a model in which cofilin is involved in the formation and disruption of the phagocytic cup as a result of its local progressive enrichment...

..These results identify InlB as the first reported non-mammalian agonist of PI 3-kinase and demonstrate similarities in the signal transduction events elicited by this bacterial protein and known agonists such as epidermal growth factor...

..By DNA-DNA hybridization, the listeriolysin O gene was detected in all L. monocytogenes strains tested, even in the nonhemolytic type strain. The gene was absent in other species of the genus Listeria...

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..The deduced amino acid sequence of this open reading frame revealed that listeriolysin O is homologous to streptolysin O and pneumolysin, although homologies were not detectable at the DNA level...

..It was renamed prtA. Northern RNA blot analysis indicated that prtA is the first gene of a 6-kb operon, suggesting that the lecithinase-negative phenotype of the mutant might be due to a polar effect of the transposon insertion...

..Our results indicate that it is a 610 amino acid protein with an apparent molecular weight of 90 kd...

..In late-exponential growth and at the beginning of the stationary phase, prfA transcripts of 1 kb are predominantly detected. Our results demonstrate that since prfA controls plcA transcription, it also regulates its own synthesis...

..These two promoter regions are separated by a palindromic sequence T-T-A-A-C-A-A/T-T-G-T-T-A-A. This palindrome was also found upstream from the ORF D promoter, suggesting that all three genes are similarly regulated...

..These results provide the first insight into the cell tropism displayed by L. monocytogenes...

..As evidenced by Southern blot analysis, inlA is part of a gene family. One of them is the gene situated directly downstream of inlA, called inlB, which also encodes a leucine-rich repeat protein...

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..Our results thus provide the first evidence for a synergy between two host factor-binding domains of a bacterial invasion protein, and reinforce similarities between InlB and mammalian growth factors...

..In a delta prfA strain, motA expression was derepressed at 37 degrees C, suggesting that PrfA, the transcriptional activator of virulence genes, downregulates motility genes in Listeria at 37 degrees C...

..Taken together, these results reveal that E-cadherin, via beta- and alpha-catenins, can trigger dynamic events of actin polymerization and membrane extensions culminating in bacterial uptake...

..This virulence gene cluster was detected exclusively in hemolytic Listeria species, Listeria ivanovii, an animal pathogen, and Listeria seeligeri, a nonpathogenic species...

..89; P = 1 x 10(-2)) and central nervous system infections were associated with group ActA2 strains (OR = 3.04; P = 1 x 10(-3)) and group ActA3 strains (OR = 3.91; P = 1 x 10(-3))...

..Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens...

..These results unravel a second L. monocytogenes species specificity critical for understanding human listeriosis and emphasize the need for developing new animal models for studying InlA and InlB functions in the same animal model...

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..These results provide the first evidence for the role of an unconventional myosin in bacterial internalization and a novel example of the exploitation of mammalian proteins, by a pathogen, to establish a successful infection...

..This motif may have important consequences for the release of surface proteins involved in interactions with eukaryotic cells...

..Our work, in addition to documenting for the first time the role of lipid rafts in Listeria entry, provides the first evidence that E-cadherin and HGF-R require lipid domain integrity for their full activity...

..The challenge is now to decipher how all of these components orchestrate themselves to permit entry into normally non-phagocytic cells...

..An affinity chromatography approach identified the rickettsial protein rOmpB as a ligand for Ku70. This is the first report of a receptor-ligand interaction involved in the internalization of any rickettsial species...

..Therefore, studies of InlB may help us to analyze the previously noticed similarities between growth factor receptor activation and phagocytosis...

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..Taken together, these results demonstrate that BSH is a novel PrfA-regulated L. monocytogenes virulence factor involved in the intestinal and hepatic phases of listeriosis...

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..Finally, beads coated with Als3 were internalized in a clathrin-dependent manner. These data indicate that C. albicans, like L. monocytogenes, hijacks the clathrin-dependent endocytic machinery to invade host cells...

..These results strongly suggest that InlH is a stress-induced surface protein that facilitates pathogen survival in tissues by tempering the inflammatory response...

..During infection, the autolytic activity of Auto may also be critical. Auto appears thus as a novel type of L. monocytogenes virulence factor...

..In myosin VIIA-defective mutants, inactivity of the vezatin-myosin VIIA complex at both sites could account for splaying out of the hair cell stereocilia...

..After E-cadherin, the receptor for internalin, gC1q-R is the second identified mammalian receptor promoting entry of L. monocytogenes into mammalian cells...

..Our results strongly support the hypothesis that PrfA is a structural and functional homologue of CAP. In addition, they establish a clear correlation between DNA binding by PrfA, virulence-gene activation, and virulence...

..A comparative proteomic analysis revealed an effect of the fri deletion on the levels of listeriolysin O and several stress proteins. Together, our study demonstrates that fri has multiple roles that contribute to Listeria virulence...

..SrtB-mediated anchoring could therefore be required to anchor surface proteins involved in the adaptation of this microorganism to different environmental conditions...

..Because SEPT2 is essential for the InlB-mediated entry of Listeria, but SEPT11 is not, our findings distinguish the roles of different mammalian septins...

..This contrasts with the generally accepted dogma but agrees with previous studies of bacterial and viral infections and also of phagocytosis...

..Listeria appears as an instrumental model for addressing critical questions concerning both the complex process of bacterial pathogenesis and also fundamental molecular processes, such as phagocytosis...

..These results suggest that MSF is a putative effector of the InlB-mediated internalization of L. monocytogenes into host cells...

..Thus, L. monocytogenes srtA is required for the cell wall anchoring of InlA and, presumably, for the anchoring of other LPXTG-containing proteins that are involved in listerial infections...

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..Together, our results reveal that Listeria, and probably other pathogens, dampen the host response by decreasing the SUMOylation level of proteins critical for infection...

..This finding highlights how subtle changes in proteins can be exploited by bacterial pathogens to establish and maintain the integrity of their specific niches...

..Here we review the pathways followed by Listeria monocytogenes to enter into non-phagocytic cells, as a model for the subversion of cellular functions to induce pathogens internalization...

..The sequence and its analysis are available at an interactive genome browser at the Institut Pasteur (http://genolist.pasteur.fr/LivaList/)...

..monocytogenes and L. ivanovii. PI-PLC activity was lost and virulence decreased when the plcA gene was disrupted in the chromosome. This suggests that the PI-PLC of L. monocytogenes might be involved in virulence...

..This diversity offers new clues about the molecular bases of Listeria pathogenesis...

..Finally, we show that septin cages entrap bacteria targeted to autophagy. Together, these results reveal an unsuspected mechanism of host defense that restricts dissemination of invasive pathogens...

..Strikingly, knockdown of the PI(4)P ligand and clathrin adaptor AP-1 strongly inhibits bacterial entry. Together, our results reveal a yet non-described role for type II PI4Ks in phagocytosis...

..This review focuses on how bacterial pathogens can interfere with host post-translational modifications to promote their own survival and replication...

..The role of actin downstream of clathrin seems to be critical for this still poorly characterized process. The historical frontier between endocytosis and phagocytosis is vanishing in the light of this new role for clathrin...

..In this issue, Niemann et al. (2007) provide the first structural evidence that InlB does not compete for the same interaction site on Met as the natural ligand HGF...

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..monocytogenes pathogenesis and particularly for the dissection of its interactions with phagocytes in vivo, a key factor of L. monocytogenes virulence...

..Together, our data unravel successive and coordinated global transcriptional changes during infection and point to previously unknown regulatory mechanisms in bacteria...

..innocua promotes bacterial adherence to human cells in vitro. Taken together, these results strongly suggest that InlJ acts as a novel L. monocytogenes sortase-anchored adhesin specifically expressed during infection in vivo...

..We previously identified SEPT9 associated with phagosomes containing latex beads coated with the Listeria surface protein InlB...

..These results indicate that L. monocytogenes-induced mobilization of extracellular Ca(2+) by LLO and activation of downstream Ca(2+)-dependent signaling are required for efficient cell invasion...

..This study identifies a second key virulence regulon in L. monocytogenes, after the prfA regulon...

..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...

..monocytogenes entry. Altogether, our results show that ARHGAP10 is a new component of cell-cell junctions that controls alpha-catenin recruitment and has a key role during L. monocytogenes uptake...

..This study reveals that PrfA can act as an activator or a repressor and suggests that PrfA may directly or indirectly activate different sets of genes in association with different sigma factors...

..In conclusion, this postgenomic approach identified InlJ as a new virulence factor among the proteins belonging to the internalin family in L. monocytogenes...

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..We also revealed a nonendocytic role for clathrin required for extracellular EPEC infections...

..monocytogenes to target and cross the placental barrier. Such a ligand-receptor interaction allowing a pathogen to specifically cross the placental villous trophoblast barrier has not been reported previously...

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..monocytogenes virulence. This is the first example of a bacterial SOD post-translationally controlled by phosphorylation, suggesting a possible new host innate mechanism to counteract a virulence factor...

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..The presence of deacetylase genes in other pathogenic bacteria indicates that PG N-deacetylation could be a general mechanism used by bacteria to evade the host innate immune system...

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..This is the first report that documents the mechanism of entry of a rickettsial species into mammalian cells...

..Vip thus appears as a new virulence factor exploiting Gp96 as a receptor for cell invasion and/or signalling events that may interfere with the host immune response in the course of the infection...

..An updated view on bacterial models responsible for important infections illustrates the key role of sRNAs in the control of pathogenesis...

..ivanovii and L. seeligeri, and sequences hybridizing to ORFX, -Y, and -Z were found in L. innocua. In contrast to this, sequences hybridizing to ldh or ORFB were detected in all Listeria species (including the nonpathogenic ones)...

..Bacteria lacking LipA are severely attenuated in virulence in vivo, thus revealing a so-far-undescribed enzymatic activity involved in Listeria infection...

..Together, our results demonstrate that L. monocytogenes utilizes multiple mechanisms to avoid destruction by the autophagy system during colonization of macrophages...

..identify mechanisms by which the Salmonella protein SipA interferes with ADF/cofilin and gelsolin function. Thus Salmonella not only triggers actin polymerization but also counteracts the major F-actin destabilizing proteins...

..Thus RickA-induced actin polymerization, by generating long actin filaments reminiscent of those present in filopodia, has potential as a tool for studying filopodia formation...