Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates

Frontiers in Microbiology

Microbiology

Mohibullah Shah¹  Aqsa Qasim¹  Asifa Sarfraz¹  Amna Anwar¹  Samavia Jaan¹  Muhammad Shehroz²  Umar Nishan³  Suvash Chandra Ojha⁴  Aqal Zaman⁵  Essam A. Ali⁶  Riaz Ullah⁷ 

[1] Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan;Department of Bioinformatics, Kohsar University Murree, Murree, Pakistan;Department of Chemistry, Kohat University of Science and Technology, Kohat, Pakistan;Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China;Department of Microbiology and Molecular Genetics, Bahauddin Zakariya University, Multan, Pakistan;Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;Medicinal Aromatic and Poisonous Plants Research Center, College of Pharmacy King Saud University, Riyadh, Saudi Arabia;

关键词: Prevotella melaninogenica;    drug target;    epitope;    peptide vaccine;    immunoinformatics;   

DOI  :  10.3389/fmicb.2023.1271798

 received in 2023-08-02, accepted in 2023-08-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen.

【 授权许可】

Unknown   
Copyright © 2023 Shah, Anwar, Qasim, Jaan, Sarfraz, Ullah, Ali, Nishan, Shehroz, Zaman and Ojha.