Guy R Cornelis

..YopP downregulates the onset of the inflammatory response by blocking the NF-kappaB and MAPK pathways. Strong arguments indicate that it is a SUMO protease. Finally, YopM has been shown to travel to the nucleus of the target cell...

..Type III secretion is key to the pathogenesis of bacteria from the Yersinia genus...

..Understanding the molecular mechanisms of this system has provided insight into the processes of phagocytosis and inflammation...

..The bacterial flagellum is evolutionarily related to the injectisome. The length of the hook is also controlled by a secreted protein. This protein acts as a substrate specificity switch and, possibly, also as a ruler...

..However, despite the ongoing concerted efforts of molecular and structural biologists, the role of many of the constituent components of this nanomachine remain unknown...

..The length of the needle is controlled by a protein that it also secreted during assembly and presumably acts as a molecular ruler...

..In contrast, YscP(1-137) -PhoA accumulated in the periplasm in the absence of YscF, suggesting that YscF is not required for the function of the export apparatus, but that its polymerization opens the secretin YscC...

..The comparative analysis of 69 16S rDNA sequences revealed the existence of C. canimorsus strains that could be misdiagnosed...

..The needle may be required for triggering type III secretion, and its length may have evolved to match specific structures at the bacterial and host cell surfaces...

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..It was essential for growth on cells and contributed to survival in mice. It thus represents a fitness factor during infection...

..We propose that covering an MLD might be an essential function of T3S effector chaperones...

..However, they could not form detectable pores in eukaryotic target cells and could not substitute for YopB and YopD for translocation of Yop effectors...

..Hence, the base of the tip complex appears to be critical for the functional insertion of YopB into the host cell membrane...

..Consistent with the observation that YopH inactivated the Akt pathway, YopH inhibited PI 3-kinase-dependent secretion of interleukin 2 and proliferation. These data reveal a new effect of YopH in Yersinia pathogenesis...

..Here, we review these different aspects focusing in open questions that promise exciting findings in the near future...

..YscP deprived of both signals could not control length, even when overproduced. We conclude from this that YscP needs to be secreted to exert its length control function but not its substrate-specificity switch function...

..In conclusion, a polysaccharide structure, likely an LPS, protects C. canimorsus from deposition of the complement MAC and from efficient phagocytosis by PMNs...

..This heteropolymeric YopBD complex could be copurified after solubilization in 0.5% dodecyl maltoside but not visualized in the electron microscope. We speculate that this complex may not be stable and rigid but only transient...

..Increasing YscP export resulted in needles with normal size, depending on the length of the ruler. Hence, the effect of the yscU(N263A) mutation on needle length was the consequence of a reduced YscP export...

..Finally, a method that allows site-directed mutagenesis is described. All these genetic tools pave the way, not only for molecular studies of the pathogenesis of C. canimorsus, but also for studies of other oral Capnocytophaga species...

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..These results highlight passive and active mechanisms of immune evasion by C. canimorsus, which may explain its capacity to escape from the host immune system...

..These data support the ruler model and show that the functional ruler has a helical structure...

..These observations suggest that both pYV plasmids are from a common ancestor but may have evolved independently following the conquest of two distant ecological niches...

..These results provide an example of how C. canimorsus neutralizes the innate immune system...

..This observation suggests that many translocation pores are not filled in the absence of YopN and thus that YopN might form a link between the needle and the pore, guiding the effectors...

..Both appear to be assembled in the same fashion. They recognize their substrate by a loose N-terminal peptide signal and the help of individual chaperones of a new type...

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..aeruginosa during chronic lung infections. These experiments uncover an important new principle of in vivo persistence, and identify the c-di-GMP network as a valid target for novel anti-infectives directed against chronic infections...

..These results show that YopH, YopT, YopO, and, in some instances, YopE act synergistically to increase the resistance of Y. enterocolitica to phagocytosis by macrophages and PMNs...

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..The experimental data are compatible with the single ruler model and not with the scenarios involving more than one ruler per needle...

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..Here, we provide evidence that the length of this needle is determined by the size of a protein, YscP, acting as a molecular ruler...

..These data show that T3S translocation is intrinsically a pro-inflammatory phenomenon. However, in the case of Yersinia, this effect is neutralized by the action of effectors...

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..pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions...

..This unique localization of LcrV may explain its crucial role in the translocation process and its efficacy as the main protective antigen against plague...

..In addition, we found that high-virulence strains inject more YopP into the cytosol of eukaryotic target cells than do low-virulence strains...

..Critical residues for nuclear targeting were identified by site-directed mutagenesis in YopMC-ter. In addition, we show that YopMC-ter NLS is crucial for the nuclear targeting of an EGFP-YopM fusion protein...

..Here, we review this enigmatic family of proteins, and discuss the experimental data supporting the roles proposed for type III chaperones...

..All the TTSSs fall into five different clusters. The phylogenetic tree of these TTSSs is completely different from the evolutionary tree based on 16S RNA, indicating that TTSSs have been distributed by horizontal transfer...

..C. canimorsus has the unusual ability to feed on host cells, including phagocytes. This capacity depends on surface-exposed glycan-foraging systems. Here we present the first complete genome sequence of a C. canimorsus strain (Cc5)...

..These results show that assembly is initiated by the formation of the OM ring and progresses inwards to the IM ring and, finally, to a large cytosolic complex...

..There are probably a few hundred effectors interfering with control and signaling in eukaryotic cells and offering a wealth of new tools to cell biologists...

..In conclusion, these results provide new insight into the mechanisms of Yersinia pathogenicity by identifying the changes in host genes expression after infection and highlight the concerted actions of the different Yop effectors...

..In agreement with this notion, increased expression of flhDC in wild-type bacteria resulted in the oversecretion of flagellins at room temperature and in decreased Yop secretion at 37 degrees C...

..Expression of this stable SycD monomer in Yersinia does not rescue the phenotype of a sycD null mutant, suggesting a physiological relevance of the dimerization interface...

..In addition, they show that the secretion apparatus can reject folded proteins if they are not deeply engaged into the injectisome...

..Hence, YscW interacts with the unassembled YscC protein and facilitates efficient oligomerization, likely at the outer membrane...

..These results highlight a previously unknown function of Rho GTPases in the activation of caspase-1 and give new insight on the role of YopE in immune-escape mechanisms of Yersinia...

..The structural similarity of SycT to other chaperones and the spatial conservation of effector-binding sites support the idea that TTS effector chaperones form a single functional and structural group...

..The hemolysis assay could be adapted for high-throughput screening of anti-infectious compounds that specifically target the type III translocon...