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Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and
Aarti Rana1, Shweta Thakur1, Nupur Bhardwaj1
1School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India.
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.
Insights
This study identifies novel surface-associated and secretory proteins (SASPs) in Mycobacterium leprae, including essential outer membrane proteins (OMPs). These OMPs contain potential epitopes for developing new immunotherapeutics against leprosy.
Area of Science:
- Microbiology and Immunology
- Computational Biology
- Protein Bioinformatics
Background:
- Leprosy, caused by Mycobacterium leprae, remains a global health challenge despite existing treatments.
- Surface-associated and secretory proteins (SASPs) are crucial for bacterial survival and are promising targets for therapeutic intervention.
Purpose of the Study:
- To perform a proteome-wide identification of SASPs in Mycobacterium leprae.
- To computationally identify immunodominant epitopes within SASPs, particularly outer membrane proteins (OMPs), for potential immunotherapeutic development.
Main Methods:
- Integrated biological knowledge with computational approaches for proteome-wide SASP identification.
- Utilized known protein sequence and structural characteristics of bacterial SASPs.
- Performed immunoinformatics analysis to assign T-cell and B-cell epitopes on identified OMPs.
Main Results:
- Identified 17 lipoproteins, 11 secretory proteins, and 19 novel outer membrane proteins (OMPs) in M. leprae, including 4 essential proteins.
- Found that 19 OMPs contain T-cell MHC class I and class II epitopes against various human HLA alleles (DR, DQ, DP).
- Detected B-cell epitopes on 11 M. leprae OMPs, indicating their potential as antigenic candidates.
Conclusions:
- The identified SASPs, especially OMPs, represent valuable targets for novel anti-leprosy strategies.
- The characterized epitopes on M. leprae OMPs provide a foundation for developing new immunotherapeutics against leprosy.
