title: Modulation of gene expression by Pseudomonas aeruginosa during chronic infection in the adult cystic fibrosis lung.
abstract: Chronic Pseudomonas aeruginosa infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa isolates undergo significant transcriptomic and proteomic modulation as they adapt to the niche environment of the CF lung and the host defences. This study characterized the in vitro virulence of isogenic strain pairs of P. aeruginosa epidemic or frequent clonal complexes (FCCs) and non-epidemic or infrequent clonal complexes (IFCCs) that were collected 5-8 years apart from five chronically infected adult CF patients. Strains showed a significant decrease in virulence over the course of chronic infection using a Caenorhabditis elegans slow-killing assay and in phenotypic tests for important virulence factors. This decrease in virulence correlated with numerous differentially expressed genes such as oprG, lasB, rsaL and lecB. Microarray analysis identified a large genomic island deletion in the IFCC strain pair that included type three secretion system effector and fimbrial subunit genes. This study presents novel in vitro data to examine the transcriptomic profiles of sequentially collected P. aeruginosa from CF adults. The genes with virulence-related functions identified here present potential targets for new therapies and vaccines against FCCs and IFCCs.
authors.affiliation: Bacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Harmer
authors.affiliation: Bacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: Khaled
authors.initials: K
authors.lastname: Alnassafi
authors.affiliation: Bacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: Honghuah
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Elkins
authors.affiliation: Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Bye
authors.affiliation: Bacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rose
authors.affiliation: School of Molecular Biosciences, University of Sydney, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Cordwell
authors.affiliation: Microbial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
authors.affiliation: Bacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: Colin
authors.initials: C
authors.lastname: Harbour
authors.affiliation: Bacterial Pathogens in Cystic Fibrosis Group, Department of Infectious Diseases and Immunology, Central Clinical School, University of Sydney, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Manos
mesh_terms: D000328:Adult; D000818:Animals; D017173:Caenorhabditis elegans / Q000382:microbiology / Q000502:physiology; D003550:Cystic Fibrosis / Q000150:complications*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D046228:Microarray Analysis; D011552:Pseudomonas Infections; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D017384:Sequence Deletion; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000032:analysis / Q000235:genetics
chemical_list: D037521:Virulence Factors