PubMed:21768350
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/21768350","sourcedb":"PubMed","sourceid":"21768350","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/21768350","text":"Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins.\nThe serine protease autotransporters of Enterobacteriaceae (SPATEs) are secreted by pathogenic Gram-negative bacteria through the autotransporter pathway. We previously classified SPATE proteins into two classes: cytotoxic (class 1) and noncytotoxic (class 2). Here, we show that Pic, a class 2 SPATE protein produced by Shigella flexneri 2a, uropathogenic and enteroaggregative Escherichia coli strains, targets a broad range of human leukocyte adhesion proteins. Substrate specificity was restricted to glycoproteins rich in O-linked glycans, including CD43, CD44, CD45, CD93, CD162 (PSGL-1; P-selectin glycoprotein ligand 1), and the surface-attached chemokine fractalkine, all implicated in leukocyte trafficking, migration, and inflammation. N-terminal sequencing of proteolytic products revealed Pic (protease involved in colonization) cleavage sites to occur before Thr or Ser residues. The purified carbohydrate sLewis-X implied in inflammation and malignancy inhibited cleavage of PSGL-1 by Pic. Exposure of human leukocytes to purified Pic resulted in polymorphonuclear cell activation, but impaired chemotaxis and transmigration; Pic-treated T cells underwent programmed cell death. We also show that the Pic-related protease Tsh/Hbp, implicated in extraintestinal infections, exhibited a spectrum of substrates similar to those cleaved by Pic. In the guinea pig keratoconjunctivitis model, a Shigella pic mutant induced greater inflammation than its parent strain. We suggest that the class-2 SPATEs represent unique immune-modulating bacterial virulence factors.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_21768350_1_0","span":{"begin":141,"end":195},"obj":"expanded"},{"id":"SS2_21768350_1_0","span":{"begin":197,"end":203},"obj":"abbr"}],"relations":[{"id":"AE1_21768350_1_0","pred":"abbreviatedTo","subj":"SS1_21768350_1_0","obj":"SS2_21768350_1_0"}],"attributes":[{"subj":"SS1_21768350_1_0","pred":"source","obj":"Allie"},{"subj":"SS2_21768350_1_0","pred":"source","obj":"Allie"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1127,"end":1133},"obj":"gene:6404"},{"id":"T1","span":{"begin":1094,"end":1104},"obj":"disease:C0006826"},{"id":"T2","span":{"begin":1127,"end":1133},"obj":"gene:6404"},{"id":"T3","span":{"begin":1094,"end":1104},"obj":"disease:C1306459"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"LitCoin-PubTator-for-Tuning","denotations":[{"id":"2","span":{"begin":38,"end":55},"obj":"OrganismTaxon"},{"id":"3","span":{"begin":71,"end":87},"obj":"OrganismTaxon"},{"id":"22","span":{"begin":458,"end":478},"obj":"OrganismTaxon"},{"id":"23","span":{"begin":516,"end":532},"obj":"OrganismTaxon"},{"id":"24","span":{"begin":567,"end":572},"obj":"OrganismTaxon"},{"id":"25","span":{"begin":664,"end":680},"obj":"ChemicalEntity"},{"id":"26","span":{"begin":870,"end":882},"obj":"DiseaseOrPhenotypicFeature"},{"id":"27","span":{"begin":1010,"end":1013},"obj":"ChemicalEntity"},{"id":"28","span":{"begin":1017,"end":1020},"obj":"ChemicalEntity"},{"id":"29","span":{"begin":1077,"end":1089},"obj":"DiseaseOrPhenotypicFeature"},{"id":"30","span":{"begin":1094,"end":1104},"obj":"DiseaseOrPhenotypicFeature"},{"id":"31","span":{"begin":1154,"end":1159},"obj":"OrganismTaxon"},{"id":"32","span":{"begin":1183,"end":1186},"obj":"ChemicalEntity"},{"id":"33","span":{"begin":1278,"end":1281},"obj":"ChemicalEntity"},{"id":"34","span":{"begin":1374,"end":1377},"obj":"GeneOrGeneProduct"},{"id":"35","span":{"begin":1413,"end":1423},"obj":"DiseaseOrPhenotypicFeature"},{"id":"36","span":{"begin":1500,"end":1510},"obj":"OrganismTaxon"},{"id":"37","span":{"begin":1511,"end":1531},"obj":"DiseaseOrPhenotypicFeature"},{"id":"38","span":{"begin":1541,"end":1549},"obj":"OrganismTaxon"},{"id":"39","span":{"begin":1577,"end":1589},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A36","pred":"tao:has_database_id","subj":"36","obj":"Tax:10141"},{"id":"A29","pred":"tao:has_database_id","subj":"29","obj":"MESH:D007249"},{"id":"A2","pred":"tao:has_database_id","subj":"2","obj":"Tax:623"},{"id":"A23","pred":"tao:has_database_id","subj":"23","obj":"Tax:562"},{"id":"A27","pred":"tao:has_database_id","subj":"27","obj":"MESH:D013912"},{"id":"A35","pred":"tao:has_database_id","subj":"35","obj":"MESH:D007239"},{"id":"A28","pred":"tao:has_database_id","subj":"28","obj":"MESH:D012694"},{"id":"A31","pred":"tao:has_database_id","subj":"31","obj":"Tax:9606"},{"id":"A30","pred":"tao:has_database_id","subj":"30","obj":"MESH:D009369"},{"id":"A24","pred":"tao:has_database_id","subj":"24","obj":"Tax:9606"},{"id":"A22","pred":"tao:has_database_id","subj":"22","obj":"Tax:42897"},{"id":"A34","pred":"tao:has_database_id","subj":"34","obj":"Gene:5962120"},{"id":"A3","pred":"tao:has_database_id","subj":"3","obj":"Tax:562"},{"id":"A39","pred":"tao:has_database_id","subj":"39","obj":"MESH:D007249"},{"id":"A38","pred":"tao:has_database_id","subj":"38","obj":"Tax:42897"},{"id":"A37","pred":"tao:has_database_id","subj":"37","obj":"MESH:D007637"},{"id":"A26","pred":"tao:has_database_id","subj":"26","obj":"MESH:D007249"},{"subj":"2","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"3","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"22","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"23","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"24","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"25","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"26","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"27","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"28","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"29","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"30","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"31","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"32","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"33","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"34","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"35","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"36","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"37","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"38","pred":"source","obj":"LitCoin-PubTator-for-Tuning"},{"subj":"39","pred":"source","obj":"LitCoin-PubTator-for-Tuning"}]},{"project":"LitCoin-Disease-Tuning-1","denotations":[{"id":"T1","span":{"begin":350,"end":359},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":533,"end":540},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":870,"end":882},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1077,"end":1089},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1094,"end":1104},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1324,"end":1329},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1413,"end":1423},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1511,"end":1531},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":1577,"end":1589},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":1606,"end":1612},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A7","pred":"ID:","subj":"T7","obj":"D009369"},{"id":"A5","pred":"ID:","subj":"T5","obj":"DISEASE"},{"id":"A6","pred":"ID:","subj":"T5","obj":"D007249"},{"id":"A1","pred":"ID:","subj":"T1","obj":"DISEASE"},{"id":"A8","pred":"ID:","subj":"T8","obj":"D003643"},{"id":"A13","pred":"ID:","subj":"T13","obj":"D013180"},{"id":"A9","pred":"ID:","subj":"T9","obj":"D007239"},{"id":"A11","pred":"ID:","subj":"T11","obj":"DISEASE"},{"id":"A12","pred":"ID:","subj":"T11","obj":"D007249"},{"id":"A2","pred":"ID:","subj":"T2","obj":"D013180"},{"id":"A3","pred":"ID:","subj":"T3","obj":"DISEASE"},{"id":"A4","pred":"ID:","subj":"T3","obj":"D007249"},{"id":"A10","pred":"ID:","subj":"T10","obj":"D007637"},{"subj":"T1","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T2","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T3","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T5","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T7","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T8","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T9","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T10","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T11","pred":"source","obj":"LitCoin-Disease-Tuning-1"},{"subj":"T13","pred":"source","obj":"LitCoin-Disease-Tuning-1"}]},{"project":"LitEisuke","denotations":[{"id":"T1","span":{"begin":350,"end":359},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":870,"end":882},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":1077,"end":1089},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":1094,"end":1104},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1511,"end":1531},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1577,"end":1589},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A2","pred":"#label","subj":"T2","obj":"D007249"},{"id":"A6","pred":"#label","subj":"T6","obj":"D007249"},{"id":"A3","pred":"#label","subj":"T3","obj":"D007249"},{"id":"A5","pred":"#label","subj":"T5","obj":"D007637"},{"id":"A4","pred":"#label","subj":"T4","obj":"D009369"},{"id":"A1","pred":"#label","subj":"T1","obj":"DISEASE"},{"subj":"T1","pred":"source","obj":"LitEisuke"},{"subj":"T2","pred":"source","obj":"LitEisuke"},{"subj":"T3","pred":"source","obj":"LitEisuke"},{"subj":"T4","pred":"source","obj":"LitEisuke"},{"subj":"T5","pred":"source","obj":"LitEisuke"},{"subj":"T6","pred":"source","obj":"LitEisuke"}]},{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":136},"obj":"Sentence"},{"id":"T2","span":{"begin":137,"end":291},"obj":"Sentence"},{"id":"T3","span":{"begin":292,"end":397},"obj":"Sentence"},{"id":"T4","span":{"begin":398,"end":601},"obj":"Sentence"},{"id":"T5","span":{"begin":602,"end":883},"obj":"Sentence"},{"id":"T6","span":{"begin":884,"end":1030},"obj":"Sentence"},{"id":"T7","span":{"begin":1031,"end":1141},"obj":"Sentence"},{"id":"T8","span":{"begin":1142,"end":1330},"obj":"Sentence"},{"id":"T9","span":{"begin":1331,"end":1492},"obj":"Sentence"},{"id":"T10","span":{"begin":1493,"end":1613},"obj":"Sentence"},{"id":"T11","span":{"begin":1614,"end":1712},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":136},"obj":"Sentence"},{"id":"T2","span":{"begin":137,"end":291},"obj":"Sentence"},{"id":"T3","span":{"begin":292,"end":397},"obj":"Sentence"},{"id":"T4","span":{"begin":398,"end":601},"obj":"Sentence"},{"id":"T5","span":{"begin":602,"end":883},"obj":"Sentence"},{"id":"T6","span":{"begin":884,"end":1030},"obj":"Sentence"},{"id":"T7","span":{"begin":1031,"end":1141},"obj":"Sentence"},{"id":"T8","span":{"begin":1142,"end":1330},"obj":"Sentence"},{"id":"T9","span":{"begin":1331,"end":1492},"obj":"Sentence"},{"id":"T10","span":{"begin":1493,"end":1613},"obj":"Sentence"},{"id":"T11","span":{"begin":1614,"end":1712},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T8","pred":"source","obj":"Inflammaging"},{"subj":"T9","pred":"source","obj":"Inflammaging"},{"subj":"T10","pred":"source","obj":"Inflammaging"},{"subj":"T11","pred":"source","obj":"Inflammaging"},{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T8","pred":"source","obj":"Inflammaging"},{"subj":"T9","pred":"source","obj":"Inflammaging"},{"subj":"T10","pred":"source","obj":"Inflammaging"},{"subj":"T11","pred":"source","obj":"Inflammaging"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#c0ec93","default":true},{"id":"DisGeNET","color":"#ec93da"},{"id":"LitCoin-PubTator-for-Tuning","color":"#93ece4"},{"id":"LitCoin-Disease-Tuning-1","color":"#ecca93"},{"id":"LitEisuke","color":"#b093ec"},{"id":"Inflammaging","color":"#93ec96"}]}]}}