title: EsiB, a novel pathogenic Escherichia coli secretory immunoglobulin A-binding protein impairing neutrophil activation.
abstract: In this study, we have characterized the functional properties of a novel Escherichia coli antigen named EsiB (E. coli secretory immunoglobulin A-binding protein), recently reported to protect mice from sepsis. Gene distribution analysis of a panel of 267 strains representative of different E. coli pathotypes revealed that esiB is preferentially associated with extraintestinal strains, while the gene is rarely found in either intestinal or nonpathogenic strains. These findings were supported by the presence of anti-EsiB antibodies in the sera of patients affected by urinary tract infections (UTIs). By solving its crystal structure, we observed that EsiB adopts a superhelical fold composed of Sel1-like repeats (SLRs), a feature often associated with bacterial proteins possessing immunomodulatory functions. Indeed, we found that EsiB interacts with secretory immunoglobulin A (SIgA) through a specific motif identified by an immunocapturing approach. Functional assays showed that EsiB binding to SIgA is likely to interfere with productive FcαRI signaling, by inhibiting both SIgA-induced neutrophil chemotaxis and respiratory burst. Indeed, EsiB hampers SIgA-mediated signaling events by reducing the phosphorylation status of key signal-transducer cytosolic proteins, including mitogen-activated kinases. We propose that the interference with such immune events could contribute to the capacity of the bacterium to avoid clearance by neutrophils, as well as reducing the recruitment of immune cells to the infection site.
  
  
  OBJECTIVE
  Pathogenic Escherichia coli infections have recently been exacerbated by increasing antibiotic resistance and the number of recurrent contagions. Attempts to develop preventive strategies against E. coli have not been successful, mainly due to the large antigenic and genetic variability of virulence factors, but also due to the complexity of the mechanisms used by the pathogen to evade the immune system. In this work, we elucidated the function of a recently discovered protective antigen, named EsiB, and described its capacity to interact with secretory immunoglobulin A (SIgA) and impair effector functions. This work unravels a novel strategy used by E. coli to subvert the host immune response and avoid neutrophil-dependent clearance.
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pastorello
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi Paccani
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosini
authors.forename: Rossella
authors.initials: R
authors.lastname: Mattera
authors.forename: Mario
authors.initials: M
authors.lastname: Ferrer Navarro
authors.forename: Dunja
authors.initials: D
authors.lastname: Urosev
authors.forename: Barbara
authors.initials: B
authors.lastname: Nesta
authors.forename: Paola
authors.initials: P
authors.lastname: Lo Surdo
authors.forename: Mariangela
authors.initials: M
authors.lastname: Del Vecchio
authors.forename: Valentina
authors.initials: V
authors.lastname: Rippa
authors.forename: Isabella
authors.initials: I
authors.lastname: Bertoldi
authors.forename: Danilo
authors.initials: D
authors.lastname: Gomes Moriel
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Laarman
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Laura
authors.initials: L
authors.lastname: Serino
authors.forename: Marco
authors.initials: M
authors.lastname: Soriani
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D057131:Immune Evasion; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D018375:Neutrophil Activation; D011487:Protein Conformation; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C585772:EsiB protein, E coli; D007071:Immunoglobulin A, Secretory; D037521:Virulence Factors