Author(s): Badrul Munir, Dwi Yuni Nur Hidayati, Tommy A Nazwar, Triyudani Mardining Raras, Sumarno Reto Prawiro

Email(s): badroel2007@yahoo.com

DOI: 10.52711/0974-360X.2023.00857   

Address: Badrul Munir1, Dwi Yuni Nur Hidayati2, Tommy A Nazwar3, Triyudani Mardining Raras4, Sumarno Reto Prawiro2
1Doctor Program Biomedical Science, Faculty Medicine, University Brawijaya, Malang Indonesia.
2Department Clinical Microbiologist, Faculty Medicine, University Brawijaya, Malang Indonesia.
3Department Neuro Surgery, Faculty Medicine, University Brawijaya, Malang Indonesia.
4Department Bio-Chemistry, Faculty Medicine, University Brawijaya, Malang Indonesia.
*Corresponding Author

Published In:   Volume - 16,      Issue - 11,     Year - 2023


ABSTRACT:
Tuberculous meningitis (TBM) is the most severe extrapulmonary infection caused by Mycobacterium tuberculosis (Mtb). An accurate diagnosis of TBM has yet to be established. Periplasmic Phosphate Binding Lipoprotein is a seropositive marker for TBM diagnosis. In the previous study, we tested antigen Ag38 recombinant from local strain and showed potential as a serodiagnosis agent candidate. This study aimed to analyze the variability gene of PstS1 and Ag38 rec and to identify the immune-dominant epitope protein PstS1 and 38recp. The PstS1 gene sequence of Mtb from the Mycobrowser database and 38kDa rec was obtained from the previous study. Variability gene of PstS1 and Ag38 rec was identified through the alignment of both genes. To predict the signal peptide in the PstS1 protein sequence, TargetP -2.0 was used. The candidate epitope on the mature protein was predicted with Bepipred 2.0 on the IEDB server. The results of Bepipred 2.0 were then compared with the Emini Surface Accessibility tool, Karplus and Schulz Flexibility tool, and Parker Hydrophilicity tool. The epitope obtained was further analyzed for antigenicity prediction. The position of the epitope on the 3D structure of the PstS1 protein was modeled with the help of the Ellipro predictor. The alignment result of gene PstS1 with Ag38reg contains an anonymous N base, but there were no mutations. Based on Target-P 2, it was found that the PstS1 protein contains a signal peptide with a truncation site at residues 24 and 25. From the results of the epitope prediction, ten candidate epitopes were obtained. Based on the antigenicity analysis, candidate epitopes were finally obtained. Of the five epitopes, two epitopes were similar to PstS1 Mtb protein crystallization results. Two epitopes are AGFASKTPANQAISMID-GPAPD and QGTIKTWDDPQIAALNPGVNLP. Thus, two potential epitope candidates are diagnostic biomarkers, namely AGFASKTPANQAISMIDGPAPD and QGTIKTWDDPQIAALNPGVNLP. However, further research is needed to validate these epitopes using the tool diagnosis TBM.


Cite this article:
Badrul Munir, Dwi Yuni Nur Hidayati, Tommy A Nazwar, Triyudani Mardining Raras, Sumarno Reto Prawiro. The Ag38-rec Mycobacterium tuberculosis Antigen as a New Candidate Marker for The Diagnostic of Tuberculosis Meningitis: In Silico Approach. Research Journal of Pharmacy and Technology. 2023; 16(11):5289-5. doi: 10.52711/0974-360X.2023.00857

Cite(Electronic):
Badrul Munir, Dwi Yuni Nur Hidayati, Tommy A Nazwar, Triyudani Mardining Raras, Sumarno Reto Prawiro. The Ag38-rec Mycobacterium tuberculosis Antigen as a New Candidate Marker for The Diagnostic of Tuberculosis Meningitis: In Silico Approach. Research Journal of Pharmacy and Technology. 2023; 16(11):5289-5. doi: 10.52711/0974-360X.2023.00857   Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-11-51


REFERENCES:
1.    Nguyen DT, Agarwal S, Graviss EA. Trends of tuberculosis  meningitis and associated mortality in Texas, 2010-2017, a large population-based analysis. Vol. 14, PLoS One. 2019.
2.    Munir B, Rianawati SB, Sutanto H, Agus Setyawan U. Mortality of central nervous system infection adult patients in Indonesia (Descriptive study in a tertier referral hospital). Vol. 381, Journal of the Neurological Sciences. 2017. p. 414.
3.    Chikoti Sneha Priya, M. Venkataswamy, Gandla Harshini, Pindrathi Pravalika, Sandhya Mandadi JB. Medicinal Plants used for the Treatment of Bacterial Meningitis. Res J Pharm Dos Forms Technol. 2019;11(3):239–44.
4.    Sourabh D Jain AKG. Chemistry of Fluoroquinones in The Management of Tuberculosis  (TB): An Overview. Asian J Pharm Res. 2021;11(1):55–9.
5.    Mohammed Musa Saaduddin, Sultana. G D. Utilization of Bedaquiline among Drug Resistant-Tuberculosis  patients. Asian J Pharm Res. 2022;12(1):132–6.
6.    Hayder Yousif Falih, Ali Hasan Ali ZAF. Study of infection levels of Mycobacterium tuberculosis  in a city of Nasiriyah – Iraq. Res J Pharm Technol. 2022;15(9):4230–4.
7.    Pukazhvanthen P, Anbarasu D, Basirudeen SAK, Raja A, Singh M. Assessing humoral immune response of 4 recombinant antigens for serodiagnosis of tuberculosis . Tuberculosis . 2014;94(6):622–33.
8.    Singh S, Singh J, Kumar S, Gopinath K, Balooni V, Singh N, et al. Poor performance of serological tests in the diagnosis of pulmonary tuberculosis : Evidence from a contact tracing field study. PLoS One. 2012;7(7):1–9.
9.    Kapopoulou A, Lew JM, Cole ST. The MycoBrowser portal: A comprehensive and manually annotated resource for mycobacterial genomes. Tuberculosis  [Internet]. 2011;91(2011):8–13. Available from: http://dx.doi.org/10.1016/j.tube.2010.09.006
10.    Bando-Campos G, Juárez-López D, Román-González SA, Castillo-Rodal AI, Olvera C, López-Vidal Y, et al. Recombinant O-mannosylated protein production (PstS-1) from Mycobacterium tuberculosis  in Pichia pastoris (Komagataella phaffii) as a tool to study tuberculosis  infection. Microb Cell Fact. 2019;18(1):1–19.
11.    Lim YJ, Choi JA, Lee JH, Choi CH, Kim HJ, Song CH. Mycobacterium tuberculosis  38-kDa antigen induces endoplasmic reticulum stress-mediated apoptosis via toll-like receptor 2/4. Apoptosis. 2013;20(3):358–70.
12.    Fan X, Li X, Wan K, Zhao X, Deng Y, Chen Z, et al. Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis . Vaccine. 2021;39(47):6860–5.
13.    Esparza M, Palomares B, García T, Espinosa P, Zenteno E, Mancilla R. PstS-1, the 38-kDa Mycobacterium tuberculosis  glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis. Scand J Immunol. 2014;81(1):46–55.
14.    Palma C, Spallek R, Piccaro G, Pardini M, Jonas F, Oehlmann W, et al. The M. tuberculosis  phosphate-binding lipoproteins PstS1 and PstS3 induce Th1 and Th17 responses that are not associated with protection against M. tuberculosis  infection. Clin Dev Immunol. 2011;2011.
15.    P. Sai Preethi MRP. Recombinant Peroxidase: Production and its Prospective Applications- A Review. Res J Pharm Tech. 2018;11(7):3186–96.
16.    Raras TYM, Santi DEP, Kusuma HC. Evaluation of immunologic response of salivary sIg-A in pediatric tuberculosis  patients to antigen Ag38-rec of Mycobacterium tuberculosis  Indonesian strain. F1000Research. 2016;4.
17.    Raras TYM, Sholeh G, Lyrawati D. Salivary sIg-A response against the recombinant Ag38 antigen of Mycobacterium tuberculosis  Indonesian strain. Vol. 7, International Journal of Clinical and Experimental Medicine. 2014. p. 129–35.
18.    Subramaniam Sivakumar SD. Identification of New Inhibitor against Mycobacterium tuberculosis  using structure based Drug Designing and Docking Studies. Res J Pharmacogn Phytochem. 2017;9(3):173–6.
19.    Maladan Y, Krismawati H, Wahyuni T, Hutapea HML, Rokhmad MF, Parikesit AA. Molecular docking analysis of the T450A mutation of the gene rpoB Mycobacterium leprae from leprosy patients in Papua, west Papua and north Maluku, Indonesia. Res J Pharm Technol. 2021;14(7):3578–84.
20.    Manojkumar R. Patle SHG. In-Silico Inhibition Studies of Phenothiazine Based Compounds on Quinolinic Acid Phosphoribosyltransferase (1QPQ) Enzyme as A Potent Anti-Tuberculosis  Agent. Asian J Res Chem. 2011;4(6):990–6.
21.    Sriroopreddy R, Raghuraman.P RR. Modeling and Docking Study of GABA-AT Protein in Mycobacterium tuberculosis  - A Computational Approach. Res J Pharm Tech. 2018;11(4):1283–8.
22.    Khoirul Anam, Bobi Prabowo, Meike Tiya Kusuma, Yuliati, Sri Winarsih, Tri Yudani Mardining Raras SRP. Multi Epitopes Potential on Surface SARS-CoV-2 Protein as a Covid-19 Vaccine Candidate. Res J Pharm Technol. 2022;15(4).
23.    Raras TYM, Lyrawati D. Cloning and expression of pab gene of M. Tuberculosis  isolated from pulmonary TB patient in E.coli DH5α. Med J Indones. 2011;20(4):247–54.
24.    Armenteros JJA, Salvatore M, Emanuelsson O, Winther O, Von Heijne G, Elofsson A, et al. Detecting sequence signals in targeting peptides using deep learning. Life Sci Alliance. 2019;2(5):1–14.
25.    Fleri W, Paul S, Dhanda SK, Mahajan S, Xu X, Peters B, et al. The immune epitope database and analysis resource in epitope discovery and synthetic vaccine design. Front Immunol. 2017;8(MAR):1–16.
26.    Javadi Mamaghani A, Arab-Mazar Z, Heidarzadeh S, Ranjbar MM, Molazadeh S, Rashidi S, et al. In-silico design of a multi-epitope for developing sero-diagnosis detection of SARS-CoV-2 using spike glycoprotein and nucleocapsid antigens. Netw Model Anal Heal Informatics Bioinforma [Internet]. 2021;10(1):1–15. Available from: https://doi.org/10.1007/s13721-021-00347-x
27.    Rana A, Thakur S, Bhardwaj N, Kumar D, Akhter Y. Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes. Pathog Dis. 2016;74(9):1–17.
28.    Le Dinh Chac, Bui Bao Thinh, Nguyen Quoc Hoang LQH. No TitleQuantification of CYFRA21-1 antigen in non-small cell lung cancer by Phage Display Real-time Immuno-PCR Method. Res J Pharm Tech. 2019;12(11):5345–50.
29.    Almagro Armenteros JJ, Tsirigos KD, Sønderby CK, Petersen TN, Winther O, Brunak S, et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat Biotechnol. 2019;37(4):420–3.
30.    Cheng P, Wang L, Gong W. In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis  Infection. 2022;13(June):1–18.
31.    Watson A, Li H, Ma B, Weiss R, Bendayan D, Abramovitz L, et al. Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis . Nat Commun. 2021;12(1).
32.    Du Y, Li H, Qin X, Wang Y, Zhang Z, Qu G, et al. Genetic diversity of antigen 38 kDa in Mycobacterium tuberculosis  strains from China. Tuberculosis . 2018;110(August 2017):20–5. Available from: https://doi.org/10.1016/j.tube.2018.03.003

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