Pseudomonas aeruginosa is among top critical nosocomial infectious agents due to its persistent infections and tendency for acquiring drug resistance mechanisms. To date, there is no vaccine available for this pathogen. We attempted to exploit the genomic and proteomic information of P. aeruginosa though reverse-vaccinology approaches to unveil the prospective vaccine candidates. P. aeruginosa strain PAO1 genome was subjected to sequential prioritization approach following genomic, proteomics and structural analyses. Among, the predicted vaccine candidates: surface components of antibiotic efflux pumps (Q9HY88, PA2837), chaperone-usher pathway components (CupC2, CupB3), penicillin binding protein of bacterial cell wall (PBP1a/mrcA), extracellular component of Type 3 secretory system (PscC) and three uncharacterized secretory proteins (PA0629, PA2822, PA0978) were identified as potential candidates qualifying all the set criteria. These proteins were then analyzed for potential immunogenic surface exposed epitopes. These predicted epitopes may provide a basis for development of a reliable subunit vaccine against P. aeruginosa.
Klebsiella pneumoniae and Mycobacterium tuberculosis coinfection is one of the most lethal combinations that has been becoming frequent yet, not diagnosed and reported properly. Due to the simultaneous occurrence of both infections, diagnosis is delayed leading to inadequate treatments and mortality. With the rise of MDR Klebsiella and Mycobacterium, a prophylactic and an immunotherapeutic vaccine has to be entailed for preemptive and adroit therapeutic approach. In this study, we aim to implement reverse vaccinology approach that encompasses a comprehensive evaluation of vital aspects of the pathogens to explore immunogenic epitopes against Omp A of Klebsiella and Rv1698, Rv1973 of Mtb that may help in vaccine development. The designed multi-epitopic vaccine was assessed for antigenicity, allergenicity and various physiochemical parameters. Molecular docking and simulations were executed to assess the immunogenicity and complex stability of the vaccine. The final multi-epitopic vaccine is validated to be highly immunogenic and can serve as a valuable proactive remedy for subject pathogens.
Pyocyanin (PCN) is a redox-active secondary metabolite produced by Pseudomonas aeruginosa as its primary virulence factor. Several studies have reported the cytotoxic potential of PCN and its role during infection establishment and progression. Considering its ability to diffuse through biological membranes, it is hypothesized that PCN can gain entry into the brain and induce oxidative stress across the blood-brain barrier (BBB), ultimately contributing towards reactive oxygen species (ROS) mediated neurodegeneration. Potential roles of PCN in the central nervous system (CNS) have never been evaluated, hence the study aimed to evaluate PCN’s probable penetration into CNS through blood-brain barrier (BBB) using both in silico and in vivo (Balb/c mice) approaches and the impact of ROS generation via commonly used tests: Morris water maze test, novel object recognition, elevated plus maze test, and tail suspension test. Furthermore, evidence for ROS generation in the brain was assessed using glutathione S-transferase assay. PCN demonstrated BBB permeability albeit in minute quantities. A significant hike was observed in ROS generation (
P
<
0.0001
) along with changes in behavior indicating PCN permeability across BBB and potentially affecting cognitive functions. This is the first study exploring the potential role of PCN in influencing the cognitive functions of test animals.
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