Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes in vivo

Abstract

Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P. aeruginosa) that has been shown to have numerous toxic effects in both in vitro and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant mediated responses. It is hypothesized that PCN can cross biological membranes and reach the systemic circulation, but no previous studies have investigated this. The aim of this study was, therefore, to quantify PCN in plasma and assess if systemic responses were occurring after localized intranasal administration in C57BL/6 J mice. This was achieved through the plasma quantification of PCN and assessment of changes to behavior using two commonly used tests, the forced swimming test and the open field test. Furthermore, evidence of systemic oxidative stress and inflammation was measured using malondialdehyde (MDA) and TNF-α post PCN exposure. PCN was found to cross into systemic circulation but in a variable manner. Furthermore, significant increases in plasma TNF-α and MDA (both p < 0.001) were observed along with changes in behavior indicative of systemic inflammatory responses.

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

“…It is difficult to consider P. aeruginosa or PCN as a sole reason for this situation as the streptococci were also isolated from crebro-spinal fluid, yet it sheds some light on probable linkage between the two. These results exhibit a similar behavioral pattern as reported by the recently published study focusing on murine behaviors, i.e., locomotor activity and immobility behavior [ 31 ].…”

“…A study by Venugopal et al reported the PCN mediated induction of oxidative stress in hippocampal cells and subsequent reversal of the redox activity due to N-acetyl-L-cysteine [ 29 , 30 ]. Arora et al have explored the systemic level inflammation and impact of PCN mediated toxicity on murine behavioral activity [ 31 ]. The study found PCN to be affecting the locomotor activity of the subjects as well as their immobility behavior.…”

Cephalosporins Interfere With Quorum Sensing and Improve the Ability of Caenorhabditis elegans to Survive Pseudomonas aeruginosa Infection

“…Previous research has shown that the pyocyanin deficient phnAB and PhzB1 mutants produce a low level of pyocyanin, leading to reduced mortality in the burn wound model of P. aeruginosa (Lau et al, 2004). Pyocyanin also induces pro-inflammatory and pro-oxidant responses leading to host cell lysis (Arora et al, 2018). Therapy targeting pyocyanin production in P. aeruginosa may suppress tissue damage during infection.…”