Identificação computacional de alvos de drogas e candidatos a vacinas em Mycoplasma genitalium

Abstract

Mycoplasma genitalium is a sexually transmitted pathogen characterized as a pleomorphic, flask-shaped, slow-growing, and obligate intracellular bacterium. It is one of the STI (sexually transmitted infections) pathogens associated with non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women, such as cervicitis, pelvic inflammatory disease (PID), and infertility. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine candidates and drug targets against five strains of M. genitalium. We identified 403 genes shared by all five strains using Orthofinder, from which 104 proteins are non-host homologous. From those, 44 exposed, secreted, or membrane, and 60 cytoplasmic proteins, as per SurfG+ analyses. Their essentiality, functionality, and structure-based binding affinity were also checked. Overall, we predicted: 19 candidate vaccine targets using Vaxign software – an ABC transporter permease; a PTS glucose EIICBA component; an adhesion P1 protein; a diacyl glyceryl transferase; an IgG blocking protein M; and 14 hypothetical proteins; and, 7 drug targets – Type I restriction-modification protein; Akylhydroperoxide reductase, Ahp; ribosome-binding factor A, RbfA; 50S ribosomal protein L32; Class Ibribonucleoside diphosphate reductase, NrdI; a DUF3217 domain-containing protein; and a hypothetical protein. Furthermore, we performed a molecular docking analysis using AutoDock Vina for each drug target against a 5008 antimicrobial natural-compounds database retrieved from the ZINC Database, selecting ZINC08636510, ZINC04235924, ZINC15709489, ZINC04237087, ZINC04236001, and ZINC35415766 as promising molecules with favorable interactions with the target’s active site residues. Finally, we predicted 14 potential vaccine targets that have not yet been described. Concerning our predicted drug targets, this study was the first to reveal both predicted hypothetical protein (WP_009885876.1) and the DUF3217 domain-containing protein (WP_009885939.1) as novel putative drug targets against M. genitalium. Altogether, both vaccine candidates and drug targets identified here may contribute to the future development of therapeutic strategies to control the spread of M. genitalium worldwide.