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A Systematic in-silico Analysis of Helicobacter pylori Pathogenic Islands for Identification of Novel Drug Target Candidates

[ Vol. 18 , Issue. 5 ]

Author(s):

Deepthi Nammi, Nagendra S. Yarla, Vladimir N. Chubarev , Vadim V. Tarasov, George E. Barreto, Amita Martin Corolina Pasupulati , Gjumrakch Aliev and Nageswara Rao Reddy Neelapu*   Pages 450 - 465 ( 16 )

Abstract:


Background: Helicobacter pylori is associated with inflammation of different areas, such as the duodenum and stomach, causing gastritis and gastric ulcers leading to lymphoma and cancer. Pathogenic islands are a type of clustered mobile elements ranging from 10-200 Kb contributing to the virulence of the respective pathogen coding for one or more virulence factors. Virulence factors are molecules expressed and secreted by pathogen and are responsible for causing disease in the host. Bacterial genes/virulence factors of the pathogenic islands represent a promising source for identifying novel drug targets.

Objective: The study aimed at identifying novel drug targets from pathogenic islands in H. pylori.

Material & Methods: The genome of 23 H. pylori strains were screened for pathogenic islands and bacterial genes/virulence factors to identify drug targets. Protein-protein interactions of drug targets were predicted for identifying interacting partners. Further, host-pathogen interactions of interacting partners were predicted to identify important molecules which are closely associated with gastric cancer.

Results: Screening the genome of 23 H. pylori strains revealed 642 bacterial genes/virulence factors in 31 pathogenic islands. Further analysis identified 101 genes which were non-homologous to human and essential for the survival of the pathogen, among them 31 are potential drug targets. Proteinprotein interactions for 31 drug targets predicted 609 interacting partners. Predicted interacting partners were further subjected to host-pathogen interactions leading to identification of important molecules like TNF receptor associated factor 6, (TRAF6) and MAPKKK7 which are closely associated with gastric cancer.

Conclusion: These provocative studies enabled us to identify important molecules in H. pylori and their counter interacting molecules in the host leading to gastric cancer and also a pool of novel drug targets for therapeutic intervention of gastric cancer.

Keywords:

Pathogenicity, Genomic islands, Virulence factors, Comparative analysis.

Affiliation:

Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, 19991 Moscow, Institute of Pharmacy and Translational Medicine, Sechenov First Moscow State Medical University, 19991 Moscow, Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriama, Bogotá D.C., Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP), GALLY” International Biomedical Research Consulting LLC, San Antonio, TX 78229, Department of Biochemistry and Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam – 534005 (AP)

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