Evaluation of Blood-Brain-Barrier Permeability, Neurotoxicity, and Potential Cognitive Impairment by Pseudomonas aeruginosa’s Virulence Factor Pyocyanin

Author:

Rashid Muhammad Ibrahim123ORCID,Rashid Habiba4ORCID,Andleeb Saadia1ORCID,Ali Amjad1ORCID

Affiliation:

1. Department of Industrial Biotechnology, Atta Ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan

2. Department of Molecular Biology & Genetics, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan

3. Department of Biotechnology, Virtual University of Pakistan, Peshawar, Pakistan

4. Department of Anatomy, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan

Abstract

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.

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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