Widespread pyocyanin over-production among isolates of a cystic fibrosis epidemic strain

The unusual phenotype was detected in at least one epidemic strain isolate from the majority of cystic fibrosis patients tested, and can be retained for up to seven years during chronic infection. Multiple sequential isolates of the epidemic strain taken from six patients over a period of up to nine years exhibited a wide range of phenotypes, including different antimicrobial susceptibilities. Our data suggest that each sputum sample contains a mixture of phenotypes and genotypes within the epidemic strain population, including within colony morphotypes. Many isolates exhibit premature (during early rather than late exponential growth) and over-production of pyocyanin, which has a number of toxic effects directly relevant to cystic fibrosis.The widespread occurrence of this unusual phenotype suggests that it may play an important role in the success of the epidemic strain.With a carrier rate of 1 in 25 and an incidence of 1 in 2,500 live births, cystic fibrosis (CF) is the most common life-threatening, recessively inherited disease amongst Caucasians. During chronic pulmonary infection, CF patients suffer decline in lung function associated with periodic exacerbations triggered by bacterial products.The most widespread CF pathogen is Pseudomonas aeruginosa, which causes infections that, once established, are impossible to eradicate.The blue, redox-active phenazine pyocyanin is secreted by P. aeruginosa under the control of its cell-density-dependent quorum sensing (QS) system [1]. Pyocyanin and its precursor phenazine-1-carboxylic acid (PCA) have a number of toxic effects relevant to CF [2,3]. Pyocyanin and PCA inhibit the beating of human respiratory cilia in vitro [4,5], and alter expression of immunomodulatory proteins by human airway epithelial cells [6]. For example, increases in IL-8 and intercellular adhesion molecule-1 (ICAM-1) expression by oxidant-dependent mechanisms have been demonstrated in vitro and in vivo [6,7]. It has also been shown that pyocyanin