Abordagens de genômica subtrativa, vacinologia reversa e imunoinformática para predição de drogas e imunógenos contra Mycoplasma pneumoniae

Abstract

Mycoplasma pneumoniae is a bacterium with unique characteristics in terms of its morphological and metabolic aspects, being one of the main pathogens associated with pneumonia, which kills about three million people annually, and which has become more incident in recent years thanks to the success pneumococcal vaccine. The peculiarities related to M.pneumoniae corroborate the resistance to certain types of antibiotics, in addition to the evident ability to resist active drugs, also, this pathogen is extremely difficult to be cultivated and used in the laboratory. The lack of pneumonia vaccines is a matter of global concern given the increase in resistant pathogens, hospital costs associated with the disease and the high mortality rate. Vaccine development methods using genomic data applying bioinformatics tools, have demonstrated to be promising strategies, mainly for microorganisms of difficult cultivation such as M. pneumoniae. Thus, through Reverse Vacinology and Immunoinformatics, a high coverage multi-epitope vaccine against M.pneumoniae was built in silico. The constructed vaccine contains epitopes belonging to highly immunogenic lipoproteins and adhesin proteins, carefully selected to belong to all 88 M.pneumoniae strains studied and to be recognized by molecules of the histocompatibility complex common in the world population. Structural tests have demonstrated stability and quality related to physical-chemical parameters. The molecular docking of the Toll-like vaccine-receptor complex, together with the simulation of molecular dynamics, demonstrated satisfactory interaction with the immune system, besides to evaluations of immunogenicity and immunological simulation. The vaccine has been shown to be safe and without allergic potential. Thus, this prospecting contributes to the development of a vaccine and prevention of pneumonia caused by M.pneumoniae, demonstrating an alternative strategy for formulating vaccines against pathogens that are difficult to cultivate furthermore, corroborating to the understanding of the interaction and the immunological mechanisms resulting from infections by M.pneumoniae.