Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach
- 38 Downloads
Shigella flexneri 2a is one of the most pathogenic bacteria among the Shigella spp., which is responsible for dysentery and causes masses of deaths throughout the world per year. A proper identification of the potential drug targets and inhibitors is crucial for the treatment of the shigellosis due to their emerging multidrug resistance (MDR) patterns. In this study, a systematic subtractive approach was implemented for the identification of novel therapeutic targets of S. flexneri 2a (301) through genome-wide metabolic pathway analysis of the essential genes and proteins. Ligand-based virtual screening and ADMET analyses were also made for the identification of potential inhibitors as well. Initially, we found 70 essential unique proteins as novel targets. After subsequent prioritization, finally we got six unique targets as the potential therapeutic targets and their three-dimensional models were built thereafter. Aspartate-β-semialdehyde dehydrogenase (ASD), was the most potent target among them and used for docking analysis through ligand-based virtual screening. The compound 3 (PubChem CID: 11319750) suited well as the best inhibitor of the ASD through ADMET and enzyme inhibition capacity analysis. To end, we hope that our proposed therapeutic targets and its inhibitors might give some breakthrough to treat shigellosis efficiently in in vitro.
KeywordsADMET Molecular docking ASD MDR Dysentery
Authors’ declares no acknowledgements for this work.
No funding was received
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
- Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y (2012) admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. ACS Publications, New York, pp 3099–3105Google Scholar
- Dutta S, Rajendran K, Roy S, Chatterjee A, Dutta P, Nair G, Bhattacharya S, Yoshida S (2002) Shifting serotypes, plasmid profile analysis and antimicrobial resistance pattern of shigellae strains isolated from Kolkata, India during 1995–2000. Epidemiol Infect 129:235–243CrossRefPubMedPubMedCentralGoogle Scholar
- Gasteiger E, Hoogland C, Gattiker A, Duvaud SE, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. Humana Press, New York, pp 571–607Google Scholar
- Hale TL, Keusch GT (1996) ShigellaGoogle Scholar
- Hasan MN, Oany AR, Hirashima A (2016) Comparative structure analysis of tyramine-β-hydroxylase from fruit fly and ADME/T-based profiling of 1-arylimidazole-2 (3H)-thiones as potential inhibitors. Int J Anal Bio-Sci 4:37–45Google Scholar
- Magrane M (2011) UniProt Knowledgebase: a hub of integrated protein data. DatabaseGoogle Scholar
- Mei Y, Liu H, Xu J (1989) Cloning and application of genus specific DNA probes for Shigella. Chin J Epidemiol 10:167–170Google Scholar
- Oany SAI, Ahmad SAI, Kibria KK, Hossain MU, Jyoti TP (2014a) A hypothetical protein of Alteromonas macleodii AltDE1 (amad1_06475) predicted to be a cold-shock protein with RNA chaperone activity. Gene Regul Syst Biol 8:141–147Google Scholar
- Oany AR, Pervin T, Mia M, Hossain M, Shahnaij M, Mahmud S, Kibria K (2017) Vaccinomics approach for designing potential peptide vaccine by targeting Shigella spp. serine protease autotransporter subfamily protein SigA. J Immunol ResGoogle Scholar
- Sander T (2001) OSIRIS property explorer. Org Chem PortalGoogle Scholar
- Sangari FJ, Pérez-Gil J, Carretero-Paulet L, García-Lobo JM, Rodríguez-Concepción M (2010) A new family of enzymes catalyzing the first committed step of the methylerythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in bacteria. Proc Natl Acad Sci 107:14081–14086CrossRefPubMedPubMedCentralGoogle Scholar
- Schrödinger L (2012) QikProp, version 3.5. New York, NYGoogle Scholar
- Schrödinger LLC (2015) The PyMOL Molecular Graphics System, version 1.8Google Scholar
- Talukder KA, Khajanchi BK, Islam MA, Islam Z, Dutta DK, Rahman M, Watanabe H, Nair GB, Sack DA (2006) Fluoroquinolone resistance linked to both gyrA and parC mutations in the quinolone resistance-determining region of Shigella dysenteriae type 1. Curr Microbiol 52:108–111CrossRefPubMedGoogle Scholar
- US Department of Health, Education, and Welfare, Public Health Service, National Communicable Disease Center (1968) Shigella surveillance report no. 15Google Scholar