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PROSPECTION OF PROTEIN CANDIDATES FOR DRUG AND VACCINE DEVELOPMENT AGAINST STREPTOCOCCUS PNEUMONIAE INFECTIONS

PROSPECTION OF PROTEIN CANDIDATES FOR DRUG AND VACCINE DEVELOPMENT AGAINST STREPTOCOCCUS PNEUMONIAE INFECTIONS

Igor Oliveira, Sarah Souza and Bernardo Santos

Streptococcus pneumoniae is a Gram-positive bacterium and the etiological agent of many diseases related to the respiratory tract (such as pneumonia), meningitis and middle ear infections. The increase in hospitalization rates resulting from pneumococcal infections and the growing reports on antibiotic-resistant pneumococcal strains lead to the development of new prophylactic and treatment methods. In this work, the subtractive genomics and reverse vaccinology approaches were considered to screen protein targets for the development of drug and vaccine against S. pneumoniae infections. The sequences of 63 complete genomes were retrieved from the NCBI database and processed for the identification of orthologous proteins encoded by all strains using OrthoFinder. The core proteome found to be not homologous to Homo sapiens comprised 287 proteins, of which 112 were predicted to be exported by S. pneumoniae and 160 were classified as cytoplasmic proteins by SurfG. As the exported bacterial proteins most likely interact with the host’s immune system, we used Vaxign to evaluate the affinity of these proteins for the histocompatibility complex (MHC). This analysis revealed 6 immunogenic proteins with great potential use in subunit vaccine development. In addition, we obtained good quality three-dimensional structure models for 33 cytoplasmic proteins using the MHOLline workflow. Among the modeled proteins, 4 drug target candidates were found using the PBIT pipeline. This selection was made according to the involvement of protein in virulence and essentiality in bacteria, and the absence of homology with proteins present in the human intestinal microbiota. These candidates will be considered for molecular docking with a library of 5,000 natural plant compounds using AutoDock Vina. The present work brings up new perspectives to control the emerging and worldwide distributed S. pneumoniae infections in human.