title: Pic, an autotransporter protein secreted by different pathogens in the Enterobacteriaceae family, is a potent mucus secretagogue.
abstract: A hallmark of enteroaggregative Escherichia coli (EAEC) infection is a formation of biofilm, which comprises a mucus layer with immersed bacteria in the intestines of patients. While studying the mucinolytic activity of Pic in an in vivo system, rat ileal loops, we surprisingly found that EAEC induced hypersecretion of mucus, which was accompanied by an increase in the number of mucus-containing goblet cells. Interestingly, an isogenic pic mutant (EAEC Δpic) was unable to cause this mucus hypersecretion. Furthermore, purified Pic was also able to induce intestinal mucus hypersecretion, and this effect was abolished when Pic was heat denatured. Site-directed mutagenesis of the serine protease catalytic residue of Pic showed that, unlike the mucinolytic activity, secretagogue activity did not depend on this catalytic serine protease motif. Other pathogens harboring the pic gene, such as Shigella flexneri and uropathogenic E. coli (UPEC), also showed results similar to those for EAEC, and construction of isogenic pic mutants of S. flexneri and UPEC confirmed this secretagogue activity. Thus, Pic mucinase is responsible for one of the pathophysiologic features of the diarrhea mediated by EAEC and the mucoid diarrhea induced by S. flexneri.
authors.affiliation: Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, México DF, Mexico. fnavarro@cell.cinvestav.mx
authors.forename: Fernando
authors.initials: F
authors.lastname: Navarro-Garcia
authors.forename: Javier
authors.initials: J
authors.lastname: Gutierrez-Jimenez
authors.forename: Carlos
authors.initials: C
authors.lastname: Garcia-Tovar
authors.forename: Luis A
authors.initials: LA
authors.lastname: Castro
authors.forename: Hector
authors.initials: H
authors.lastname: Salazar-Gonzalez
authors.forename: Vanessa
authors.initials: V
authors.lastname: Cordova
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000145:classification / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D020397:Goblet Cells / Q000166:cytology / Q000187:drug effects; D007082:Ileum / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D009093:Mucus / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012763:Shigella flexneri / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C541114:Pic protein, E coli; D012697:Serine Endopeptidases