Phenotypic adaptation of Pseudomonas aeruginosa to the Cystic Fibrosis lung environment

Abstract

Pseudomonas aeruginosa is one of the major pathogens of the Cystic Fibrosis (CF) lung, infecting up to 50% of CF patients. The CF lung is a complex and heterogeneous environment in which P. aeruginosa establishes long term chronic infections through extensive adaptation after an initial acute infection stage. The phenotypic adaptation of P. aeruginosa was investigated through two different sets of clinical isolates. The first was a previously available set of 154 longitudinally collected isolates from 18 patients. The second consisted of multiple isolates collected from 7 early and 17 chronically infected patient samples. These 593 isolates were specifically collected for this study. Multi-locus variable number tandem repeat analysis (MLVA) genotyping showed that all isolates from individual patients typed were clonally related. Through the measurement of multiple phenotypes linked to virulence (motility, proteases, pyocyanin, pyoverdine, hydrogen cyanide, biofilm formation and speed of growth) and regulatory quorum sensing molecules, the evolution of the phenotypes between stages of infection was first assessed. The measurements for all phenotypes were significantly (p<0.05) lower in chronic stage isolates than early stage isolates. Results showed statistically significant (p<0.01) positive moderate correlations between QS regulated phenotypic and the QS autoinducer molecules. The hypothesis that within-patient diversity is greater than between-patient diversity was tested. The results showed that between-patient diversity was in fact greater than within-patient diversity for all phenotypes for both early and chronic stages of infection. However, significant (p<0.05) within-patient diversity in almost all patients was observed for one phenotype or more, and within-patient diversity was higher in chronic stage infection samples than in early stage samples. This study contributes to the body of work demonstrating the degree and complexity of adaptation of P. aeruginosa and brings further insight into the extent of diversity within and between patients.