Cell membrane Complex Enzyme Eukaryotic cell or cell component Microbe-host cell complex Microorganism or its component Other Other -- ion Pathway or action Protein Protein or gene Protein or gene complex Protein or protein complex Bacterial membrane or virus envelope Cell membrane Cytoplasm Eukaryotic cell or cell component Extracellular Golgi Golgi membrane Intercellular Intracellular Mitochondria Nucleocapsid/Cytoplasm Organelle Organelle -- Cell membrane Organelle -- Endoplasmic reticulum Organelle -- ER Organelle -- Golgi Organelle -- Golgi membrane Organelle -- Nucleus Organelle -- Phagolysosome Organelle -- Phagosome Organelle -- Ribosome Other Phagolysosome Phagosome Chaperone Defense, immunity protein Enzyme Enzyme activator Enzyme inhibitor Genomic S segment Infection Ligand binding or carrier Motor Nucleic acid binding Other Signal transducer Toxicity Transcription factor binding Transcription regulation Transporter Unknown IC Inferred by Curator IDA Inferred from Direct Assay IEA Inferred from Electronic Annotation IEP Inferred from Expression Pattern IGI Inferred from Genetic Interaction IMP Inferred from Mutant Phenotype IPI Inferred from Physical Interaction ISS Inferred from Sequence or Structural Similarity NAS Non-traceable Author Statement ND No biological Data available RCA inferred from Reviewed Computational Analysis TAS Traceable Author Statement NR Not Recorded Cornelis GR, Boland A, Boyd AP, Geuijen C, Iriarte M, Neyt C, Sory MP, Stainier I Microbiology and molecular biology reviews : MMBR The virulence plasmid of Yersinia, an antihost genome 1998 9841674 PubMed Holmstrom A, Olsson J, Cherepanov P, Maier E, Nordfelth R, Pettersson J, Benz R, Wolf-Watz H, Forsberg A Molecular microbiology LcrV is a channel size-determining component of the Yop effector translocon of Yersinia 2001 11169103 PubMed Cornelis GR Folia microbiologica The Yersinia Yop virulon, a bacterial system to subvert cells of the primary host defense 1998 9717252 PubMed Barz C, Abahji TN, Trulzsch K, Heesemann J FEBS letters The Yersinia Ser/Thr protein kinase YpkA/YopO directly interacts with the small GTPases RhoA and Rac-1 200029 11018537 PubMed Grosdent N, Maridonneau-Parini I, Sory MP, Cornelis GR Infection and immunity Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis 2002 12117925 PubMed Yao T, Mecsas J, Healy JI, Falkow S, Chien Y The Journal of experimental medicine Suppression of T and B lymphocyte activation by a Yersinia pseudotuberculosis virulence factor, yopH 19991 10544205 PubMed Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE Science Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector 199917 10489373 PubMed Orth K Current opinion in microbiology Function of the Yersinia effector YopJ 2002 11834367 PubMed Denecker G, Declercq W, Geuijen CA, Boland A, Benabdillah R, van Gurp M, Sory MP, Vandenabeele P, Cornelis GR The Journal of biological chemistry Yersinia enterocolitica YopP-induced apoptosis of macrophages involves the apoptotic signaling cascade upstream of bid 20018 11279213 PubMed Butler T Transactions of the Royal Society of Tropical Medicine and Hygiene The black death past and present. 1. Plague in the 1980s 1989 2617596 PubMed Gradon JD Current infectious disease reports Plague Pneumonia 2002 12015918 PubMed Rollins SE, Rollins SM, Ryan ET American journal of clinical pathology Yersinia pestis and the plague 2003 12951845 PubMed Aepfelbacher M, Trasak C, Ruckdeschel K Thrombosis and haemostasis Effector functions of pathogenic Yersinia species 2007 17849040 PubMed Kerschen EJ, Cohen DA, Kaplan AM, Straley SC Infection and immunity The plague virulence protein YopM targets the innate immune response by causing a global depletion of NK cells 2004 15271919 PubMed Yersinia Type III Secretion System Function: Transporter. The 70-kb virulence plasmid enables Yersinia to survive and multiply in the lymphoid tissues of their host. Yersinia cells use a type III secretion system to translocate the effector proteins, called Yops (Yersinia outer proteins), into the host cells.This system consists of the Yop proteins and their dedicated type III secretion apparatus, called Ysc. The Ysc apparatus is composed of some 25 proteins. Most of the Yops fall into two groups. Some of them are the intracellular effectors (YopE, YopH, YopJ/YopP, YopM, and YopT), while the others (YopB, YopD, and LcrV) form the translocation apparatus that is deployed at the bacterial surface to deliver the effectors into the eukaryotic cells, across their plasma membrane (Cornelis et al., 1998). YopB, YopD, LcrV secretion Function: Transporter. YopB and YopD are both required for translocation of Yop effectors across the eukaryotic cell membrane. YopB and YopD appear to be associated in the bacterium prior to their secretion. LcrV interacts with both YopB and YopD, and it is necessary for the secretion of YopB and YopD.(Holmstrom et al., 2001) Translocon structure formation Function: Transporter. YopB and YopD could insert together in the eukaryotic membrane to form the putative pore. LcrV could be a functional element of the translocation apparatus. LcrV initiates the translocation process, and the role of the surface-exposed LcrV is to conduct the translocators to the target cell membrane. These proteins are also required for channel formation infected host cells (Holmstrom et al., 2001). YopE, H, J/P, M, T translocation into host cells Function: Enzyme activator. A type III secretion system/translocon is responsible for the translocation of the Yersinia Yop effectors into the host cell. Once inside the host cell, YopH, YopE, YopJ/YopP, YpkA, YopT and YopM carry out disruption of signalling cascades that activate the processes of phagocytosis, cytokine release and respiratory burst. Some of these effectors are known to function in the downregulation of critical signalling cascades of the immune system.(Cornelis, 1998) YpkA translocation into host cells Function: Enzyme activator. YpkA is an essential virulence determinant for Yersinia infection. YpkA is translocated to the host plasma membrane. YpkA, a serine/threonine kinase, disrupts the actin cytoskeleton. YpkA most probably functions by phosphorylating proteins that are important in the regulation of the actin cytoskeleton within the host cell.(Barz et al., 2000) YopE, T, YpkA. Cellular modification of GTPases. Cytoskeletal rearrangements Function: Enzyme activator. YopE inactivates the Rho family of GTPases, resulting in altered actin cytoskeleton. YopT is a protein that causes a modification of the actin cytoskeleton. Disruption of the actin cytoskeleton by YpkA might be mediated by its ability to interact with the small GTPase RhoA, which plays an important role in actin dynamics within the host cells. These events result in the actin cytoskeleton modification via the activation of the Rho family of GTPases, which includes Rho, Rac and Cdc42 and eventually lead to the cytoskeletal rearrangements.(Grosdent et al., 2002) Yop effectors. Yersinia - induced phagocytosis inhibition Function: Defense, immunity protein. Once inside the host cell, the Yop effectors (YopH, YopE, YopT, and YpkA) inhibit cytoskeleton dynamics and block the ability of the cell to respond to infection. They contribute to the strong resistance of Yersinia cells to phagocytosis by macrophages. The YopH effector is among the most powerful phosphotyrosine phosphatases (PTPase) known and also acts to inhibit phagocytosis. The YopH, YopT, YpkA protein effectors, and, in some instances, YopE act synergistically to increase the resistance of Yersinia to phagocytosis by macrophages and PMNs.(Grosdent et al., 2002) Yop effectors. Yersinia - induced host immune response inactivation Function: Defense, immunity protein. Yop effectors promote intracellular survival of Yersinia by counteracting the normal proinflammatory response of cells to infection and presumably reduce neutrophil recruitment to the site of infection. YopH is implicated in inhibiting the immune response. The phosphatase activity of YopH is essential for suppressing T-cell cytokine production. This downregulation of T-cell signaling is caused by dephosphorylation of tyrosine residues on proteins in the T-cell receptor complex. YopH inhibits the production of MCP-1. YopJ/YopP is the only Yop effector that causes an anti-inflammatory effect and is responsible for the induction of apoptosis in macrophages. Macrophages infected with Yersinia secreting YopJ/YopP also lack the usual activation of MAPKs. These processes allow the pathogen to survive and multiply extracellularly in the host lymphoid tissue (Yao et al., 1999)(Orth et al., 1999). YopJ/YopP. MAPK kinase function inactivation Function: Enzyme inhibitor. Yersinia infection results in a severe inhibition of multiple MAPK signalling pathways in macrophages. Translocation of YopJ/YopP through the type III secretion machinery is required for this inhibition. YopJ/YopP can bind to multiple members of the MAPK kinase superfamily, including MKKs and I kB kinase complex, and suppress their activation via phosphorylation.(Orth et al., 1999) YopJ/YopP. NF-kB transcription factor function inactivation Function: Transcription factor binding. YopJ/YopP can block NF-kB activation through the inhibition of I kB kinase ? (IKK?) degradation. YopJ/YopP is a cysteine protease that cleaves a reversible post-translational modification in the form of ubiquitin or a ubiquitin-like protein. This in turn prevents the migration of the transcription factor NF- kB to the nucleus.(Orth, 2002) YopJ/YopP - induced macrophage cell apoptosis Function: . Yersinia infection causes macrophage apoptosis. YopJ/YopP is the only Yop effector required for the induction of apoptosis in macrophages. YopJ/YopP induces apoptosis in macrophages, either directly by acting of inactivation of NF- kB or indirectly by blocking the synthesis of NF- kB–dependent antiapoptotic factors.(Denecker et al., 2001) Development of septicemia/pneumonia Function: . Upon translocation of the Yersinia effectors into the target host cells, these molecules cripple the target cells by blocking phagocytosis, destroying the host defense system and inducing macrophage cell apoptosis. Primary septicemia develops in the absence of apparent regional lymphadenitis. Secondary septicemia occurs when lymphatic and other host defenses are breached and Yersinia cells multiply within the bloodstream. Of all forms of theYersinia infection, pneumonia develops most rapidly and is most frequently fatal (Butler, 1989)(Gradon, 2002)(Rollins et al., 2003). YopM of Yersinia pestis was found recently to induce depletion of NK cells in a model of septicemia (Aepfelbacher et al., 2007). YopM, is necessary for virulence in a mouse model of septicemic plague, but its pathogenic function is unknown (Kerschen et al., 2004).