Quantitative Proteomics of the 2016 WHO Neisseria gonorrhoeae Reference Strains Surveys Vaccine Candidates and Antimicrob a Resistance Determinants
Quantitative Proteomics of the 2016 WHO Neisseria gonorrhoeae Reference Strains Surveys Vaccine Candidates and Antimicrob a Resistance Determinants
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DOI：
10.1074/mcp.ra118.001125
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发表时间：
2019-01-01
影响因子：
7
通讯作者：
Unemo, Magnus
中科院分区：
文献类型：
--
作者：
El-Rami, Fadi E.;Zielke, Ryszard A.;Unemo, Magnus
性传播疾病淋病（病原体：淋病奈瑟菌）由于其对生殖健康的影响、高发病率、广泛的抗菌素耐药性（AMR）以及缺乏疫苗，仍然是全球紧迫的公共卫生威胁。为了挖掘淋病抗原并增强我们在蛋白质组水平上对淋球菌抗菌素耐药性的了解，我们对不同的淋球菌菌株（n = 15）进行了首次大规模的蛋白质组学分析，包括2016年世界卫生组织（WHO）参考菌株。这些菌株显示了所有现有的抗菌素耐药性谱——通过表型鉴定和参考基因组发表建立的——并用于实验室调查的质量保证。在这里，这些分离物进行了亚细胞分离和标记，串联质量标签结合质谱和多组合生物信息学。我们的分析在细胞包膜和细胞质亚蛋白质组中分别检测到904和723种常见蛋白质。我们确定了9种新的淋病候选疫苗。研究了新抗原和先前选择抗原的表达和保存。此外，首次使用定量蛋白质组学对已建立的淋球菌AMR决定因素进行了评估。WHO_F_00238、WHO_F_00635c、WHO_F_00745、WHO_F_01139、WHO_F_01144c和WHO_F_01126这6个新蛋白在所有菌株中差异表达，表明它们代表了全球蛋白质组学AMR标记，表明它们倾向于发展或补偿gonococcus AMR，并且/或作为新的抗菌靶点。最后，基于分离物定义的抗生素图谱和共同差异表达蛋白的表型聚类在已建立的和蛋白质组衍生的AMR特征之间产生了7个匹配的聚类。总之，我们的调查为淋球菌疫苗和抗菌素耐药性研究工作提供了参考蛋白质组学数据库，使微生物学、临床或流行病学项目成为可能，并提高了世卫组织参考菌株的实用性。
The sexually transmitted disease gonorrhea (causative agent: Neisseria gonorrhoeae) remains an urgent public health threat globally because of 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 data bank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.