A biomedical perspective of pyocyanin from Pseudomonas aeruginosa: its applications and challenges

Abstract

Pyocyanin is a bioactive pigment produced by Pseudomonas aeruginosa. It is an important virulence factor that plays a critical role in P. aeruginosa infections as a redox-active secondary metabolite and a quorum sensing (QS) signaling molecule. Pyocyanin production from chorismic acid requires the involvement of two homologous operons, phz1 and phz2, which are activated by QS regulatory proteins. Pyocyanin inhibits the proliferation of bacterial, fungal, and mammalian cells by inducing oxidative stress due to which it acts as a potent antibacterial, antifungal, and anticancer agent. Its potential role as a neuroprotectant needs further exploration. However, pyocyanin exacerbates the damaging effects of nosocomial infections caused by P. aeruginosa in immunocompromised individuals. Further, cystic fibrosis (CF) patients are highly susceptible to persistent P. aeruginosa infections in the respiratory system. The bacterial cells form colonies and three interconnected QS networks-pqs, las, and rhl-get activated, thus stimulating the cells to produce pyocyanin which exacerbates pulmonary complications. As an opportunistic pathogen, P. aeruginosa produces pyocyanin to impede the recovery of injuries like burn wounds through its anti-proliferative activity. Moreover, pyocyanin plays a vital role in compounding P. aeruginosa infections by promoting biofilm formation. This review begins with a brief description of the characteristics of pyocyanin, its activity, and the different aspects of its production including its biosynthesis, the role of QS, and the effect of environmental factors. It then goes on to explore the potential applications of pyocyanin as a biotherapeutic molecule while also highlighting the biomedical challenges and limitations that it presents.

Keywords: Antibacterial; Anticancer; Antifungal; Neuroprotective; Pseudomonas aeruginosa; Pyocyanin.

Fig. 1

Chemical structure of pyocyanin

Fig. 2

UV–Vis absorption spectrum of pyocyanin (Ohfuji et al. 2004)

Fig. 3

Positive and negative effects of pyocyanin throughout the P. aeruginosa life cycle (Meirelles and Newman 2018)

Fig. 4

Biosynthetic pathway for the production of pyocyanin by P. aeruginosa

Fig. 5

Quorum sensing (QS) mechanism of P. aeruginosa (Vetrivel et al. 2021)

Fig. 6

Production of ROS by pyocyanin

Fig. 7

Anticancer property of pyocyanin

Fig. 8

Graphs showing change in cell viability of different cell lines on increasing pyocyanin concentration (Abdelaziz et al. ; Koyun et al. 2022)

Fig. 9

Neuroprotective property of pyocyanin

Fig. 10

Antibacterial property of pyocyanin

Fig. 11

MIC of pyocyanin against different food-borne pathogenic bacteria (Hamad et al. 2020)

Fig. 12

Antifungal activity of pyocyanin

Fig. 13

Mechanism of action of pyocyanin in the respiratory epithelium of CF patients (Rada and Leto 2013)

Fig. 14

Pyocyanin-mediated release of eDNA via cell lysis due to oxidative stress