title: Broad spectrum activity of a lectin-like bacterial serine protease family on human leukocytes.
abstract: The serine protease autotransporter from Enterobacteriaceae (SPATE) family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system.
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America; Unidad Academica de Ciencias Quimicas, Universidad Autonoma de Zacatecas, Zacatecas, Mexico.
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: Ayala-Lujan
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America; Department of Immunology and Microbiology, University of Maryland at Baltimore, Baltimore, Maryland, United States of America.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Vijayakumar
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Araceli E
authors.initials: AE
authors.lastname: Santiago
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ruiz-Perez
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D059748:Proteolysis; D016415:Sequence Alignment; D057057:Serine Proteases / Q000032:analysis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D057057:Serine Proteases