Identification of Immunogenic Salmonella enterica Serotype Typhi Antigens Expressed in Chronic Biliary Carriers of S. Typhi in Kathmandu, Nepal
Year: 2013
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage. METHODOLOGY/PRINCIPAL FINDINGS: To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present. CONCLUSIONS/SIGNIFICANCE: Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers.
Source: PLoS neglected tropical diseases
Authors: Richelle C. Charles, Tania Sultana, Mohammad Murshid Alam, Yanan Yu, Ying Wu-Freeman, Meagan Kelly Bufano, Sean M. Rollins, Lillian Tsai, Jason B. Harris, Regina C. LaRocque, Daniel T. Leung, W. Abdullah Brooks, Tran Vu Thieu Nga, Sabina Dongol, Buddha Basnyat, Stephen B. Calderwood, Jeremy Farrar, Farhana Khanam, John S. Gunn, Firdausi Qadri, Stephen Baker, Edward T. Ryan
Institutions: Harvard University, Massachusetts General Hospital, International Centre for Diarrhoeal Disease Research, Fitchburg State University, Oxford University Clinical Research Unit, Wellcome Trust, Patan Academy of Health Sciences, Oxford University Clinical Research Unit Nepal, University of Oxford, The Ohio State University, London School of Hygiene & Tropical Medicine
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,670
Funders: Howard Hughes Medical Institute, Massachusetts General Hospital, Wellcome Trust, Harvard Global Health Institute, International Centre for Diarrhoeal Disease Research, Bangladesh, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Fogarty International Center
Awards: Protecutive immunity to human cholera in Bangladesh, Improving diagnostic capabilities for typhoid fever, High throughput NAPPA-proteoimmunomics and Vibrio cholerae vaccine development, Viet Nam Major Overseas Programme Core Grant Renewal 2010-2015., G1313941599, G1510978416, G4273498612, High-throughput proteomic study of protective immunity in human cholera infection, G4497380281, G5551172042, G647409134, Fogarty International Clinical Research Scholars Support Center @ Vanderbilt-AAMC, T-cell immune responses to Vibrio cholerae infection, The epidemiology, genomics and longitudinal immune response of Shigella infections in Vietnamese children., Identification of human gene polymorphisms related to Vibrio cholerae infection, Improving diagnostic capabilities for typhoid fever, G8001904788, Immune Responses to Vibrio Cholerae in Children, G8739757399, G9000303568, International research training program in vaccine development and public health, G96359071
OpenAlex ID: W2154149210