title: Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes.
abstract: For centuries, Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs). Exploiting the known protein sequence and structural characteristics shared by the SASPs from bacteria, 17 lipoproteins, 11 secretory and 19 novel OMPs (including 4 essential proteins) were identified in M. leprae As OMPs represent the most exposed antigens on the cell surface, their immunoinformatics analysis showed that the identified 19 OMPs harbor T-cell MHC class I epitopes and class II epitopes against HLA-DR alleles (54), while 15 OMPs present potential T-cell class II epitopes against HLA-DQ alleles (6) and 7 OMPs possess T-cell class II epitopes against HLA-DP alleles (5) of humans. Additionally, 11 M. leprae OMPs were found to have B-cell epitopes and these may be considered as prime candidates for the development of new immunotherapeutics against M. leprae.
authors.affiliation: School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India.
authors.forename: Aarti
authors.initials: A
authors.lastname: Rana
authors.affiliation: School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Thakur
authors.affiliation: School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India.
authors.forename: Nupur
authors.initials: N
authors.lastname: Bhardwaj
authors.affiliation: School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India.
authors.forename: Devender
authors.initials: D
authors.lastname: Kumar
authors.affiliation: School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India yusuf@daad-alumni.de.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Akhter
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D015415:Biomarkers; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007167:Immunotherapy; D007918:Leprosy / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology* / Q000378:metabolism; D020543:Proteome
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D015415:Biomarkers; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D020543:Proteome
keywords: Mycobacterium leprae; antigen; diagnostic markers; epitopes; outer membrane proteins; vaccine