title: Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa isolates have a highly conserved core genome representing up to 90% of the total genomic sequence with additional variable accessory genes, many of which are found in genomic islands or islets. The identification of the Liverpool Epidemic Strain (LES) in a children's cystic fibrosis (CF) unit in 1996 and its subsequent observation in several centers in the United Kingdom challenged the previous widespread assumption that CF patients acquire only unique strains of P. aeruginosa from the environment. To learn about the forces that shaped the development of this important epidemic strain, the genome of the earliest archived LES isolate, LESB58, was sequenced. The sequence revealed the presence of many large genomic islands, including five prophage clusters, one defective (pyocin) prophage cluster, and five non-phage islands. To determine the role of these clusters, an unbiased signature tagged mutagenesis study was performed, followed by selection in the chronic rat lung infection model. Forty-seven mutants were identified by sequencing, including mutants in several genes known to be involved in Pseudomonas infection. Furthermore, genes from four prophage clusters and one genomic island were identified and in direct competition studies with the parent isolate; four were demonstrated to strongly impact on competitiveness in the chronic rat lung infection model. This strongly indicates that enhanced in vivo competitiveness is a major driver for maintenance and diversifying selection of these genomic prophage genes.
authors.affiliation: Division of Medical Microbiology and Genitourinary Medicine, University of Liverpool, Liverpool L69 3GA, United Kingdom.
authors.forename: Craig
authors.initials: C
authors.lastname: Winstanley
authors.forename: Morgan G I
authors.initials: MG
authors.lastname: Langille
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Fothergill
authors.forename: Irena
authors.initials: I
authors.lastname: Kukavica-Ibrulj
authors.forename: Catherine
authors.initials: C
authors.lastname: Paradis-Bleau
authors.forename: François
authors.initials: F
authors.lastname: Sanschagrin
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.forename: Geoff L
authors.initials: GL
authors.lastname: Winsor
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Nicola
authors.initials: N
authors.lastname: Lennard
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bignell
authors.forename: Louise
authors.initials: L
authors.lastname: Clarke
authors.forename: Kathy
authors.initials: K
authors.lastname: Seeger
authors.forename: David
authors.initials: D
authors.lastname: Saunders
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Fiona S L
authors.initials: FS
authors.lastname: Brinkman
authors.forename: Roger C
authors.initials: RC
authors.lastname: Levesque
mesh_terms: D000818:Animals; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004739:England / Q000453:epidemiology; D036781:Fimbriae Proteins / Q000235:genetics; D005798:Genes, Bacterial; D005814:Genes, Viral; D016680:Genome, Bacterial; D006801:Humans; D005810:Multigene Family; D016296:Mutagenesis; D019081:O Antigens / Q000235:genetics; D039002:Prophages / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D011552:Pseudomonas Infections / Q000453:epidemiology / Q000382:microbiology*; D017105:Pseudomonas Phages / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000821:virology*; D051381:Rats; D014774:Virulence / Q000235:genetics
chemical_list: D019081:O Antigens; D036781:Fimbriae Proteins