PMID- 28352257 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 8 DP - 2017 TI - A Novel Pan-Genome Reverse Vaccinology Approach Employing a Negative-Selection Strategy for Screening Surface-Exposed Antigens against leptospirosis. PG - 396 LID - 10.3389/fmicb.2017.00396 [doi] LID - 396 AB - Reverse vaccinology (RV) has been widely used for screening of surface-exposed proteins (PSEs) of important pathogens, including outer membrane proteins (OMPs), and extracellular proteins (ECPs) as potential vaccine candidates. In this study, we applied a novel RV negative strategy and a pan-genome analysis for screening of PSEs from 17 L. interrogans strains covering 11 predominately epidemic serovars and 17 multilocus typing (MLST) sequence types (STs) worldwide. Our results showed, for instance, out of a total of 633 predicted PSEs in strain 56601, 92.8% were OMPs or ECPs (588/633). Among the 17 strains, 190 core PSEs, 913 dispensable PSEs and 861 unique PSEs were identified. Of the 190 PSEs, 121 were further predicted to be highly antigenic and thus may serve as potential vaccine candidates against leptospirosis. With the exception of LipL45, OmpL1, and LigB, the majority of the 121 PSEs were newly identified antigens. For example, hypothetical proteins BatC, LipL71, and the OmpA family proteins sharing many common features, such as surface-exposed localization, universal conservation, and eliciting strong antibody responses in patients, are regarded as the most promising vaccine antigens. Additionally, a wide array of potential virulence factors among the predicted PSEs including TonB-dependent receptor, sphingomyelinase 2, leucine-rich repeat protein, and 4 neighboring hypothetical proteins were identified as potential antigenicity, and deserve further investigation. Our results can contribute to the prediction of suitable antigens as potential vaccine candidates against leptospirosis and also provide further insights into mechanisms of leptospiral pathogenicity. In addition, our novel negative-screening strategy combined with pan-genome analysis can be a routine RV method applied to numerous other pathogens. FAU - Zeng, LingBing AU - Zeng L AD - Department of Laboratory Medicine, the First Affiliated Hospital of NanChang UniversityNanchang, China; Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of MedicineShanghai, China. FAU - Wang, Dongliang AU - Wang D AD - CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology Beijing, China. FAU - Hu, NiYa AU - Hu N AD - Department of Laboratory Medicine, the First Affiliated Hospital of NanChang University Nanchang, China. FAU - Zhu, Qing AU - Zhu Q AD - Department of Laboratory Medicine, the First Affiliated Hospital of NanChang University Nanchang, China. FAU - Chen, Kaishen AU - Chen K AD - Department of Laboratory Medicine, the First Affiliated Hospital of NanChang University Nanchang, China. FAU - Dong, Ke AU - Dong K AD - Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China. FAU - Yao, YuFeng AU - Yao Y AD - Deparment of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College Kunming, China. FAU - Guo, XiaoKui AU - Guo X AD - Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China. FAU - Chang, Yung-Fu AU - Chang YF AD - Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University Ithaca, NY, USA. FAU - Zhu, YongZhang AU - Zhu Y AD - Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine Shanghai, China. LA - eng PT - Journal Article DEP - 20170314 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC5348505 OTO - NOTNLM OT - L. interrogans OT - negative selection strategy OT - reverse vaccinology (RV) OT - surface-exposed proteins OT - vaccine candidate EDAT- 2017/03/30 06:00 MHDA- 2017/03/30 06:01 PMCR- 2017/03/14 CRDT- 2017/03/30 06:00 PHST- 2016/03/25 00:00 [received] PHST- 2017/02/27 00:00 [accepted] PHST- 2017/03/30 06:00 [entrez] PHST- 2017/03/30 06:00 [pubmed] PHST- 2017/03/30 06:01 [medline] PHST- 2017/03/14 00:00 [pmc-release] AID - 10.3389/fmicb.2017.00396 [doi] PST - epublish SO - Front Microbiol. 2017 Mar 14;8:396. doi: 10.3389/fmicb.2017.00396. eCollection 2017.