Mycoplasma genitalium: A comparative genomics study of metabolic pathways for the identification of drug and vaccine targets

Abstract

Increasing emergence of antibiotic-resistant pathogenic microorganisms is one of the biggest challenges for biomedical research and drug development. Traditional drug discovery methods are time-consuming, expensive and often yield few drug targets. In contrast, advances in complete genome sequencing, bioinformatics and cheminformatics represent an attractive alternative approach to identify drug targets worthy of experimental follow-up. Mycoplasma genitalium is a human parasitic pathogen that is associated with several sexually transmitted diseases. Recently, emergence of treatment-resistant isolates has been reported, which raises serious concern and a need for identification of additional drug targets. In the present study, a systematic workflow consisting of comparative genomics, metabolic pathways analysis and additional drug prioritizing parameters was defined for the identification of novel drug and vaccine targets that are essential for M. genitalium, but absent in its human host. In silico analyses and manual mining identified 79 proteins of M. genitalium, which showed no similarity to human proteins. Among these, 67 proteins were identified as non-homologous essential proteins that could serve as potential drug and vaccine targets. Subcellular localization, molecular weight, and three-dimensional structural characteristics that could facilitate filtering of attractive drug targets were also calculated for the non-homologous essential proteins. Enzymes from thiamine biosynthesis, protein biosynthesis, and folate biosynthesis were identified as attractive candidates for drug development. Furthermore, druggability of each of the identified drug targets was also evaluated by the DrugBank database. Results from this study could facilitate selection of M. genitalium proteins for entry into drug design and vaccine production pipelines.