Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets

Aqsa Qasim; Samavia Jaan; Tehreem Ul Wara; Muhammad Shehroz; Umar Nishan; Sulaiman Shams; Mohibullah Shah; Suvash Chandra Ojha

doi:10.3389/fcimb.2023.1017315

Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets

Front Cell Infect Microbiol. 2023 Mar 24:13:1017315. doi: 10.3389/fcimb.2023.1017315. eCollection 2023.

Authors

Aqsa Qasim¹, Samavia Jaan¹, Tehreem Ul Wara¹, Muhammad Shehroz², Umar Nishan³, Sulaiman Shams⁴, Mohibullah Shah¹, Suvash Chandra Ojha⁵

Affiliations

¹ Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
² Department of Bioinformatics, Kohsar University, Murree, Pakistan.
³ Department of Chemistry, Kohat University of Science & Technology, Kohat, Pakistan.
⁴ Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, Pakistan.
⁵ Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Abstract

Neisseria gonorrhoeae is an emerging multidrug resistance pathogen that causes sexually transmitted infections in men and women. The N. gonorrhoeae has demonstrated an emerging antimicrobial resistance against reported antibiotics, hence fetching the attention of researchers to address this problem. The present in-silico study aimed to find putative novel drug and vaccine targets against N. gonorrhoeae infection by the application of bioinformatics approaches. Core genes set of 69 N. gonorrhoeae strains was acquired from complete genome sequences. The essential and non-homologous metabolic pathway proteins of N. gonorrhoeae were identified. Moreover, different bioinformatics databases were used for the downstream analysis. The DrugBank database scanning identified 12 novel drug targets in the prioritized list. They were preferred as drug targets against this bacterium. A viable vaccine is unavailable so far against N. gonorrhoeae infection. In the current study, two outer-membrane proteins were prioritized as vaccine candidates via reverse vaccinology approach. The top lead B and T-cells overlapped epitopes were utilized to generate a chimeric vaccine construct combined with immune-modulating adjuvants, linkers, and PADRE sequences. The top ranked prioritized vaccine construct (V7) showed stable molecular interaction with human immune cell receptors as inferred during the molecular docking and MD simulation analyses. Considerable response for immune cells was interpreted by in-silico immune studies. Additional tentative validation is required to ensure the effectiveness of the prioritized vaccine construct against N. gonorrhoeae infection. The identified proteins can be used for further rational drug and vaccine designing to develop potential therapeutic entities against the multi-drug resistant N. gonorrhoeae.

Keywords: Neisseria gonorrhoeae; chimaric vaccine; epitope; multi-drug resistant; novel drug target.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Computers
Data Analysis
Female
Genomics
Gonorrhea* / drug therapy
Gonorrhea* / microbiology
Humans
Male
Molecular Docking Simulation
Neisseria gonorrhoeae* / genetics

Grants and funding

This study was funded by the Doctoral Research Fund awarded to SCO.