Tag Archives

One Article

Posted by rsg2sec on

PREDICTION OF PROTEIN CANDIDATES FOR DRUG AND VACCINE DEVELOPMENT AGAINST PSEUDOMONAS AERUGINOSA INFECTIONS

PREDICTION OF PROTEIN CANDIDATES FOR DRUG AND VACCINE DEVELOPMENT AGAINST PSEUDOMONAS AERUGINOSA INFECTIONS

Sarah Souza, Igor Oliveira and Letícia Carvalho

Pseudomonas aeruginosa is a Gram-negative bacterium widely distributed in the environment. As an opportunistic pathogen, P. aeruginosa is associated with high morbidity and mortality in immunocompromised patients worldwide, especially those already affected by cystic fibrosis. Its extensive resistance to antimicrobials and the lack of an effective vaccine leads to an urgency in searching for new therapeutic options. The present work aimed to use the subtractive genomics and
reverse vaccinology approaches for the screening of protein targets to develop drug and vaccine against P. aeruginosa. The sequences of 174 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 the human host comprised 695 proteins, of which 385 were predicted as cytoplasmic proteins and 310 as proteins exported by P. aeruginosa according to SurfG. We were able to obtain good quality three -dimensional structure models for 71 cytoplasmic proteins using the MHOLline workflow. Among the modeled proteins, 5 best 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, besides the absence of homology with proteins produced by the intestinal microbiota in human. Using Vaxign, 44 candidate antigens were found among the proteins exported by P. aeruginosa, of which 7 presented greater potential for the development of subunit vaccines. Next, the drug target candidates will be used for molecular docking
with a library of 5,000 natural plant compounds using AutoDock Vina. Also, immunoinformatic approaches will be considered to select the best antigen epitopes for the formulation of a chimeric subunit vaccine. This work brings up