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Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants
Pharmaceutical Sciences, Oregon State University, United States of America.
College of Pharmacy, Oregon State University, United States of America.
World Health Organization, Geneva, Switzerland.
Department of Pharmaceutical Sciences, Oregon State University, United States of America; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton OR, United States.
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2019 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 1, p. 127-150Article in journal (Refereed) Published
Abstract [en]

The sexually transmitted disease gonorrhea (causative agent: Neisseria gonorrhoeae) remains an urgent public health threat globally due to its reproductive health repercussions, high incidence, widespread antimicrobial resistance (AMR), and absence of a vaccine. To mine gonorrhea antigens and enhance our understanding of gonococcal AMR at the proteome level, we performed the first large-scale proteomic profiling of a diverse panel (n=15) of gonococcal strains, including the 2016 World Health Organization (WHO) reference strains. These strains show all existing AMR profiles - established through phenotypic characterization and reference genome publication - and are intended for quality assurance in laboratory investigations. Herein, these isolates were subjected to subcellular fractionation and labeling with tandem mass tags coupled to mass spectrometry and multi-combinatorial bioinformatics. Our analyses detected 904 and 723 common proteins in cell envelope and cytoplasmic subproteomes, respectively. We identified nine novel gonorrhea vaccine candidates. Expression and conservation of new and previously selected antigens were investigated. In addition, established gonococcal AMR determinants were evaluated for the first time using quantitative proteomics. Six new proteins, WHO_F_00238, WHO_F_00635c, WHO_F_00745, WHO_F_01139, WHO_F_01144c, and WHO_F_01126, were differentially expressed in all strains, suggesting that they represent global proteomic AMR markers, indicate a predisposition toward developing or compensating gonococcal AMR, and/or act as new antimicrobial targets. Finally, phenotypic clustering based on the isolates' defined antibiograms and common differentially expressed proteins yielded seven matching clusters between established and proteome-derived AMR signatures. Together, our investigations provide a reference proteomics databank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2019. Vol. 18, no 1, p. 127-150
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Immunology in the medical area
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URN: urn:nbn:se:oru:diva-69896DOI: 10.1074/mcp.RA118.001125ISI: 000454764200012PubMedID: 30352803Scopus ID: 2-s2.0-85057604568OAI: oai:DiVA.org:oru-69896DiVA, id: diva2:1261146
Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2019-01-17Bibliographically approved

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Unemo, Magnus

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