Pyocyanin

Pyocyanin (PCN) is a blue redox-active secondary metabolite produced by Pseudomonas aeruginosa. PCN is readily recovered in large quantities in sputum from patients patients infected with P. aeruginosa [1]. PCN interferes with multiple cellular functions [1].

In vitro: Pyocyanin induced a time- and concentration-dependent acceleration of neutrophil apoptosis. Treatment with 50 μM pyocyanin resulted in a 10-fold induction of apoptosis at 5h(p < 0.001). The concentration 50 (μM) has been documented in sputum from patients colonized with P. aeruginosa. Pyocyanin showed no effects on the apoptosis of monocyte-derived macrophages or airway epithelial cells at time points up to 24 h [2]. Pyocyanin resulted in gradual onset of slowing and ultimate widespread ciliostasis with epithelial disruption [3].

In vivo: In a murine model of acute pneumonia, pyocyanin production by P. aeruginosa suppressed the acute inflammatory response by pathogen-driven acceleration of neutrophil apoptosis and by reducing local inflammation. Intratracheal instillation of wild-type and pyocyanin-deficient strains of P. aeruginosa caused a rapid increase in bronchoalveolar lavage neutrophil counts up to 18 h after infection.

In wild-type infection, the number of neutrophil declined steadily. neutrophil numbers increased up to 48 h in mice infected with pyocyanin-deficient P. aeruginosa. Pyocyanin production was associated with reduced bacterial clearance from the lungs. The concentration of potent neutrophil chemokines (MIP-2, KC) and cytokines (IL-6, IL-1β) were significantly lower in wild-type when compared with that of phenazine-deficient strain-infected mice at 18 h [4]. Pyocyanin (600 ng) resulted in 60% reduction in tracheal mucus velocity at 3 h, and no recovery occurred [5].

References:
[1] Lau G W, Hassett D J, Ran H, et al.  The role of pyocyanin in Pseudomonas aeruginosa infection[J]. Trends in molecular medicine, 2004, 10(12): 599-606.
[2] Usher L R, Lawson R A, Geary I, et al.  Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection[J]. The Journal of Immunology, 2002, 168(4): 1861-1868.
[3] Wilson R, Pitt T, Taylor G, et al.  Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro[J]. Journal of Clinical Investigation, 1987, 79(1): 221.
[4] Allen L, Dockrell D H, Pattery T, et al.  Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo[J]. The Journal of Immunology, 2005, 174(6): 3643-3649.
[5] Munro N C, Barker A, Rutman A, et al.  Effect of pyocyanin and 1-hydroxyphenazine on in vivo tracheal mucus velocity[J]. Journal of applied physiology, 1989, 67(1): 316-323.