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

Mohibullah Shah; Amna Anwar; Aqsa Qasim; Samavia Jaan; Asifa Sarfraz; Riaz Ullah; Essam A Ali; Umar Nishan; Muhammad Shehroz; Aqal Zaman; Suvash Chandra Ojha

doi:10.3389/fmicb.2023.1271798

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

Front Microbiol. 2023 Sep 22:14:1271798. doi: 10.3389/fmicb.2023.1271798. eCollection 2023.

Authors

Affiliations

¹ Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
² Medicinal Aromatic and Poisonous Plants Research Center, College of Pharmacy King Saud University, Riyadh, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁴ Department of Chemistry, Kohat University of Science and Technology, Kohat, Pakistan.
⁵ Department of Bioinformatics, Kohsar University Murree, Murree, Pakistan.
⁶ Department of Microbiology and Molecular Genetics, Bahauddin Zakariya University, Multan, Pakistan.
⁷ Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Abstract

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.

Keywords: Prevotella melaninogenica; drug target; epitope; immunoinformatics; peptide vaccine.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding this research (IFKSUOR3-020-1). This research also supported by the Doctoral Research Fund awarded to SO.