Journal of Environment and Sociobiology

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Insights Into The Structure And Dynamics Of Shigella Invasion Proteins For Use As Potential Drug Targets


Affiliations
1 Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata-700016, India
2 Department of Zoology, Government General Degree College, Singur, West Bengal, India
     

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The Gram-negative bacteria, Shigella spp. has always been a pathogen of concern in the context of global burden of diarrheal diseases, with recent surveys taking the annual incidence of shigellosis to roughly 125 million cases worldwide. The scenario has been further worsened by the frequent reports on isolation of multi drug resistant (MDR) Shigella strains, showing resistance against potent antibiotics including the 3rd generation cephalosporins as well. With the recent years witnessing a growing interest in the discovery of novel drugs, this work has scrutinized the structural nitty-gritty of the predominant virulence factors in Shigella, viz. the invasion plasmid antigens IpaA, IpaB, IpaC and IpaD, that are evidenced to have multifaceted role in the pathogenesis cascade, to explore their potential as promising therapeutic targets. In this work we report the 3D models of the different invasion proteins using comparative modeling and a comprehensive structural evaluation protocol for evaluating their stability as drug targets. Our data suggest significant potential of these invasion proteins to serve as future drug targets, thus opening up the avenue for further investigations.

Keywords

Shigella, Invasion proteins, Structural analysis, Drug targets, In-silico.
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  • Baker, S. and The, H. C. 2018. Recent insights into Shigella: a major contributor to the global diarrhoeal disease burden. Curr. Opin. Infect. Dis., 31(5): 449-454.

  • Benkert, P., Biasini, M. and Schwede, T. 2011. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics (Oxford, England), 27(3): 343-350.

  • Davis, I. W., Leaver-Fay, A., Chen, V. B., Block, J. N., Kapral, G. J., Wang, X., Murray, L. W., Arendall, W. B. III., Snoeyink, J., Richardson, J. S. and Richardson, D. C. 2007. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res., 35 (Web Server issue): W375-W383.

  • Ghosh, S., Pazhani, G. P., Chowdhury, G., Guin, S., Dutta, S., Rajendran, K., Bhattacharya, M. K., Takeda, Y., Niyogi, S. K., Nair, G. B. and Ramamurthy, T. 2011 Genetic characteristics and changing antimicrobial resistance among Shigella spp. isolated from hospitalized diarrhoeal patients in Kolkata, India. J. Med. Microbiol., 60(10): 1460-1466.

  • Lampel, K. A., Formal, S. B. and Maurelli, A. T. 2018. A Brief History of Shigella. EcoSal Plus, 8(1): 10.1128/ecosalplus.ESP-0006-2017.

  • Liu, J., Platts-Mills, J. A., Juma, J., Kabir, F., Nkeze, J., Okoi, C., Operario, D. J., Uddin, J., Ahmed, S., Alonso, P. L., Antonio, M., Becker, S. M., Blackwelder, W. C., Breiman, R. F., Faruque, A. S. G., Fields, B., Gratz, J., Haque, R., Hossain, A., Hossain, M. J. Houpt, E. R. 2016. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study. Lancet (London, England), 388(10051): 1291-1301.

  • McGuffin, L. J., Adiyaman, R., Maghrabi, A., Shuid, A. N., Brackenridge, D. A., Nealon, J. O. and Philomina, L. S. 2019. IntFOLD: an integrated web resource for high performance protein structure and function prediction. Nucleic Acids Res., 47(W1): W408-W413.

  • Muthuirulandi Sethuvel, D. P., Devanga Ragupathi, N. K., Anandan, S., Veeraraghavan, B. 2017. Update on: Shigella new serogroups/serotypes and their antimicrobial resistance. Lett. Appl. Microbiol. 64(1): 8-18.

  • Nüesch-Inderbinen, M., Heini, N., Zurfluh, K., Althaus, D., Hächler, H. and Stephan, R. 2016. Shigella Antimicrobial Drug Resistance Mechanisms, 2004-2014. Emerg. Infect. Dis., 22(6): 1083-1085.

  • Trofa, A. F., Ueno-Olsen, H., Oiwa, R. and Yoshikawa, M. 1999. Dr. Kiyoshi Shiga: discoverer of the dysentery bacillus. Clin. Infect. Dis., 29(5): 1303-1306.

  • Varney, A. M., Smitten, K. L., Thomas, J. A., and McLean, S. 2021. Transcriptomic analysis of the activity and mechanism of action of a Ruthenium (II)-based antimicrobial that induces minimal evolution of pathogen resistance. ACS Pharmacol Ttransl. Sci., 4(1): 168-178.

  • Yuriev, E., Agostino, M. and Ramsland, P. 2011. Challenges and advances in computational docking. J. Mol. Recognit., 24(2): 149-164.


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  • Insights Into The Structure And Dynamics Of Shigella Invasion Proteins For Use As Potential Drug Targets

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Authors

Sarmishta Mukhopadhyay
Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata-700016, India
Sayak Ganguli
Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata-700016, India
Santanu Chakrabarti
Department of Zoology, Government General Degree College, Singur, West Bengal, India

Abstract


The Gram-negative bacteria, Shigella spp. has always been a pathogen of concern in the context of global burden of diarrheal diseases, with recent surveys taking the annual incidence of shigellosis to roughly 125 million cases worldwide. The scenario has been further worsened by the frequent reports on isolation of multi drug resistant (MDR) Shigella strains, showing resistance against potent antibiotics including the 3rd generation cephalosporins as well. With the recent years witnessing a growing interest in the discovery of novel drugs, this work has scrutinized the structural nitty-gritty of the predominant virulence factors in Shigella, viz. the invasion plasmid antigens IpaA, IpaB, IpaC and IpaD, that are evidenced to have multifaceted role in the pathogenesis cascade, to explore their potential as promising therapeutic targets. In this work we report the 3D models of the different invasion proteins using comparative modeling and a comprehensive structural evaluation protocol for evaluating their stability as drug targets. Our data suggest significant potential of these invasion proteins to serve as future drug targets, thus opening up the avenue for further investigations.

Keywords


Shigella, Invasion proteins, Structural analysis, Drug targets, In-silico.

References