title: Identification of in vivo-induced bacterial protein antigens during human infection with Salmonella enterica serovar Typhi.
abstract: We applied an immunoscreening technique, in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed during human infection with Salmonella enterica serovar Typhi, the cause of typhoid fever. We were able to assign a functional classification to 25 of 35 proteins identified by IVIAT. Of these 25, the majority represent proteins with known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in fimbrial structure and biogenesis, antimicrobial resistance, heavy metal transport, bacterial adhesion, and extracytoplasmic substrate trafficking as well as secreted hydrolases. The 10 remaining antigens represent proteins with unknown functions. Of the 35 identified antigens, four had no immunoreactivity when probed with control sera from individuals never exposed to serovar Typhi organisms; these four included PagC, TcfB, and two antigens of unknown function encoded by STY0860 and STY3683. PagC is a virulence factor known to be upregulated in vivo in S. enterica serovar Typhimurium infection of mice. TcfB is the major structural subunit of a fimbrial operon found in serovar Typhi with no homolog in serovar Typhimurium organisms. By examining differential immunoreactivities in acute- versus convalescent-phase human serum samples, we found specific anti-PagC and anti-TcfB immunoglobulin G responses in patients with serovar Typhi bacteremia. Serovar Typhi antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and they may have diagnostic, therapeutic, or preventive uses.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. jbharris@partners.org
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
authors.forename: Andrea
authors.initials: A
authors.lastname: Baresch-Bernal
authors.forename: Sean M
authors.initials: SM
authors.lastname: Rollins
authors.forename: Ashfaqul
authors.initials: A
authors.lastname: Alam
authors.forename: Regina C
authors.initials: RC
authors.lastname: LaRocque
authors.forename: Margaret
authors.initials: M
authors.lastname: Bikowski
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Peppercorn
authors.forename: Martin
authors.initials: M
authors.lastname: Handfield
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Hillman
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hohmann
authors.forename: Robert F
authors.initials: RF
authors.lastname: Breiman
authors.forename: W Abdullah
authors.initials: WA
authors.lastname: Brooks
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
mesh_terms: D000942:Antigens, Bacterial / Q000032:analysis* / Q000145:classification / Q000235:genetics; D001426:Bacterial Proteins / Q000032:analysis* / Q000145:classification / Q000235:genetics; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood; D008565:Membrane Proteins / Q000032:analysis* / Q000145:classification / Q000235:genetics; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology*; D014435:Typhoid Fever / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D008565:Membrane Proteins