title: Characterization of anti-Salmonella enterica serotype Typhi antibody responses in bacteremic Bangladeshi patients by an immunoaffinity proteomics-based technology.
abstract: Salmonella enterica serotype Typhi is the cause of typhoid fever and a human-restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform immunoaffinity proteomics-based technology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S. Typhi to capture S. Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S. Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S. Typhi and S. Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S. Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. rccharles@partners.org
authors.forename: Richelle C
authors.initials: RC
authors.lastname: Charles
authors.forename: Alaullah
authors.initials: A
authors.lastname: Sheikh
authors.forename: Bryan
authors.initials: B
authors.lastname: Krastins
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
authors.forename: M Saruar
authors.initials: MS
authors.lastname: Bhuiyan
authors.forename: Regina C
authors.initials: RC
authors.lastname: LaRocque
authors.forename: Tanya
authors.initials: T
authors.lastname: Logvinenko
authors.forename: David A
authors.initials: DA
authors.lastname: Sarracino
authors.forename: Indira T
authors.initials: IT
authors.lastname: Kudva
authors.forename: Jana
authors.initials: J
authors.lastname: Eisenstein
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Podolsky
authors.forename: Anuj
authors.initials: A
authors.lastname: Kalsy
authors.forename: W Abdullah
authors.initials: WA
authors.lastname: Brooks
authors.forename: Albrecht
authors.initials: A
authors.lastname: Ludwig
authors.forename: Manohar
authors.initials: M
authors.lastname: John
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000302:isolation & purification; D016470:Bacteremia / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology* / Q000302:isolation & purification; D001459:Bangladesh; D002648:Child; D002675:Child, Preschool; D002846:Chromatography, Affinity; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D012485:Salmonella typhi / Q000276:immunology*; D014435:Typhoid Fever / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M