Integrated computational approaches assisted development of a novel multi-epitope vaccine against MDR Streptococcus pseudopneumoniae

Abordagens computacionais integradas que auxiliaram no desenvolvimento de uma nova vacina multiepítopo contra Streptococcus pseudopneumoniae multirresistente

Abstract

The emergence of antibiotic resistance (AR) in bacteria is becoming an alarming health concern because it allows them to adapt themselves to changing environments. It is possible to prevent the spread of AR in many ways, such as reducing antibiotic misuse in human and veterinary medicine. Streptococcus pseudopneumoniae is one of these AR bacterial species that can cause pneumonia in humans and is responsible for high mortality and morbidity rates. It is oval shaped gram-positive bacterium that shows resistance to several antibiotics like penicillin, tetracycline, ciprofloxacin, erythromycin, and co-trimoxazale and no approved vaccine is available to overcome diseases of the pathogen. Thus, substantial efforts are necessary to select protective antigens from a whole genome of pathogens that are easily tested experimentally. The in silico designed vaccine was safe and potent in immunizing individuals against the aforementioned pathogens. Herein, we utilized a subtractive genomic approach to identify potential epitope-based vaccine candidates against S. pseudopneumoniae. In total, 50850 proteins were retrieved from the NCBI, representing the complete genome of S. pseudopneumoniae. Out of the total, CD-HIT analysis identified 1022 proteins as non-redundant and 49828 proteins as redundant and further subjected for subcellular localization in which bulk of proteins was located in the cytoplasm, with seven extracellular proteins (penicillin-binding protein, alpha-amylase, solute-binding protein, hypothetical protein, CHAP domain-containing protein, polysaccharide deacetylase family protein, hypothetical protein). Six immune cells epitopes (SNLQSENDRL, RNDSLQKQAR, NPTTTSEGF, KVKKKNNKK, AYSQGSQKEH, and SVVDQVSGDF) were predicted with the help of the IEDB server. To design a multi-epitopes vaccine these immune cell epitopes were together by GPGPG and adjuvant linker to enhance immune response efficacy. The 3D structure of the designed vaccine was modeled and conducted molecular docking and dynamic simulation studies were to check the binding efficacy with immune cells receptor and dynamic behavior of the docked complex. Finally, we concluded that the designed vaccine construct can provoke a proper and protective immune response against S. pseudopneumoniae.

Keywords:
Streptococcus pseudopneumoniae ; immunoinformatics; epitope-based vaccine; docking; MD simulations