title: SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection.
abstract: Salmonella enterica is a major cause of morbidity worldwide and mortality in children and immunocompromised individuals in sub-Saharan Africa. Outer membrane proteins of Salmonella are of significance because they are at the interface between the pathogen and the host, they can contribute to adherence, colonization, and virulence, and they are frequently targets of antibody-mediated immunity. In this study, the properties of SadA, a purported trimeric autotransporter adhesin of Salmonella enterica serovar Typhimurium, were examined. We demonstrated that SadA is exposed on the Salmonella cell surface in vitro and in vivo during infection of mice. Expression of SadA resulted in cell aggregation, biofilm formation, and increased adhesion to human intestinal Caco-2 epithelial cells. Immunization of mice with folded, full-length, purified SadA elicited an IgG response which provided limited protection against bacterial challenge. When anti-SadA IgG titers were enhanced by administering alum-precipitated protein, a modest additional protection was afforded. Therefore, despite SadA having pleiotropic functions, it is not a dominant, protective antigen for antibody-mediated protection against Salmonella.
authors.affiliation: School of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Dhaarini
authors.initials: D
authors.lastname: Raghunathan
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wells
authors.forename: Faye C
authors.initials: FC
authors.lastname: Morris
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shaw
authors.forename: Saeeda
authors.initials: S
authors.lastname: Bobat
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Peters
authors.forename: Gavin K
authors.initials: GK
authors.lastname: Paterson
authors.forename: Karina Tveen
authors.initials: KT
authors.lastname: Jensen
authors.forename: Denisse L
authors.initials: DL
authors.lastname: Leyton
authors.forename: Jessica M A
authors.initials: JM
authors.lastname: Blair
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Browning
authors.forename: John
authors.initials: J
authors.lastname: Pravin
authors.forename: Adriana
authors.initials: A
authors.lastname: Flores-Langarica
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Hitchcock
authors.forename: Claudia T P
authors.initials: CT
authors.lastname: Moraes
authors.forename: Roxane M F
authors.initials: RM
authors.lastname: Piazza
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: Mark A
authors.initials: MA
authors.lastname: Webber
authors.forename: Robin C
authors.initials: RC
authors.lastname: May
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Piddock
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Ian R
authors.initials: IR
authors.lastname: Henderson
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000534:Alum Compounds; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D018441:Biofilms; D018938:Caco-2 Cells; D048168:Escherichia coli K12 / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010802:Phylogeny; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D000534:Alum Compounds; D007074:Immunoglobulin G; D008565:Membrane Proteins; C041524:aluminum sulfate