Evaluation of Pyocyanin induced systemic pathogenicity of Pseudomonas aeruginosa
Muhammad Ibrahim Rashid1, Saadia Andleeb1, Amjad Ali1
1Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Abstract:
Pseudomonas aeruginosa (PA) is one of the most clinically significant nosocomial infectious agents. Clinical significance of this bacterium is intensified due to the phenomenon of its natural tendency for acquiring drug resistance mechanisms. PA produces pyocyanin (PCN), an important redox-active virulence factor. PCN has been detected in higher quantities in sputum samples of PA infected Cystic Fibrosis patients. PCN producing PA strains were isolated and characterized. Genomic 16s rRNA gene segment was amplified and sequenced (GenBank accession # jx280426). PCN was extracted and purified. In silico analysis yielded permeability and cytotoxic potential of PCN in modeled cell lines. PCN has high intestinal absorption, plasma protein binding potential, and permeability across biological membranes. Oral toxicity study in in silico rodent model classified PCN in class IV 'harmful if swallowed' (ld50 0.3-2g/kg). Cytotoxicity was assessed by oxidative stress levels in different organs in balb/c mice induced by intra peritoneal PCN injection. Significant alterations in oxidative stress levels in different organs of balb/c mice were observed. Increased levels of oxidative stress were observed in lungs, and heart, lower in liver and spleen while muscle tissues showed no significant difference in comparison to control.
Insights
Pseudomonas aeruginosa produces pyocyanin, a virulence factor found in cystic fibrosis patients. This study shows pyocyanin has harmful oral toxicity and causes oxidative stress in mouse organs, particularly the lungs and heart.
Area of Science:
- Microbiology
- Toxicology
- Biochemistry
Background:
- Pseudomonas aeruginosa (PA) is a significant nosocomial pathogen known for developing drug resistance.
- Pyocyanin (PCN), a redox-active virulence factor produced by PA, is found in higher concentrations in cystic fibrosis patients' sputum.
- Understanding PCN's toxicity is crucial for managing PA infections.
Purpose of the Study:
- To characterize pyocyanin (PCN) produced by Pseudomonas aeruginosa.
- To investigate the in silico and in vivo toxicity of PCN.
- To assess the impact of PCN on oxidative stress in different organs.
Main Methods:
- Isolation and characterization of PCN-producing PA strains.
- Genomic sequencing of the 16s rRNA gene segment.
- In silico analysis of PCN's absorption, binding, and permeability.
- In silico oral toxicity assessment using a rodent model.
- In vivo assessment of PCN-induced oxidative stress in balb/c mice.
Main Results:
- In silico analysis predicted high intestinal absorption, plasma protein binding, and membrane permeability for PCN.
- In silico oral toxicity studies classified PCN as 'harmful if swallowed' (Class IV, LD50 0.3-2g/kg).
- In vivo studies showed significant alterations in oxidative stress levels in mouse organs, with increased levels in lungs and heart, and decreased levels in the liver and spleen.
Conclusions:
- Pyocyanin exhibits significant toxicological properties, including harmful oral toxicity and the induction of oxidative stress.
- The findings highlight PCN as a key virulence factor contributing to PA pathogenesis, particularly in the context of cystic fibrosis.
- Further research into PCN's mechanisms of toxicity is warranted to develop targeted therapeutic strategies.
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