title: Virulence factor expression patterns in Pseudomonas aeruginosa strains from infants with cystic fibrosis.
abstract: Pseudomonas aeruginosa is the leading cause of morbidity and mortality in cystic fibrosis (CF). This study examines the role of organism-specific factors in the pathogenesis of very early P. aeruginosa infection in the CF airway. A total of 168 longitudinally collected P. aeruginosa isolates from children diagnosed with CF following newborn screening were genotyped by pulsed-field gel electrophoresis (PFGE) and phenotyped for 13 virulence factors. Ninety-two strains were identified. Associations between virulence factors and gender, exacerbation, persistence, timing of infection and infection site were assessed using multivariate regression analysis. Persistent strains showed significantly lower pyoverdine, rhamnolipid, haemolysin, total protease, and swimming and twitching motility than strains eradicated by aggressive antibiotic treatments. Initial strains had higher levels of virulence factors, and significantly higher phospholipase C, than subsequent genotypically different strains at initial isolation. Strains from males had significantly lower pyoverdine and swimming motility than females. Colony size was significantly smaller in strains isolated during exacerbation than those isolated during non-exacerbation periods. All virulence factors were higher and swimming motility significantly higher in strains from bronchoalveolar lavage (BAL) and oropharyngeal sites than BAL alone. Using unadjusted regression modelling, age at initial infection and age at isolation of a strain showed U-shaped profiles for most virulence factors. Among subsequent strains, longer time since initial infection meant lower levels of most virulence factors. This study provides new insight into virulence factors underpinning impaired airway clearance seen in CF infants, despite aggressive antibiotic therapy. This information will be important in the development of new strategies to reduce the impact of P. aeruginosa in CF.
authors.affiliation: Sydney CF Research Group, Department of Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, 2006, Australia, jim.manos@sydney.edu.au.
authors.forename: J
authors.initials: J
authors.lastname: Manos
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: B R
authors.initials: BR
authors.lastname: Rose
authors.forename: C E
authors.initials: CE
authors.lastname: Wainwright
authors.forename: I B
authors.initials: IB
authors.lastname: Zablotska
authors.forename: J
authors.initials: J
authors.lastname: Cheney
authors.forename: L
authors.initials: L
authors.lastname: Turnbull
authors.forename: C B
authors.initials: CB
authors.lastname: Whitchurch
authors.forename: K
authors.initials: K
authors.lastname: Grimwood
authors.forename: C
authors.initials: C
authors.lastname: Harmer
authors.forename: S N
authors.initials: SN
authors.lastname: Anuj
authors.forename: C
authors.initials: C
authors.lastname: Harbour
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000382:microbiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011552:Pseudomonas Infections / Q000150:complications / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D016032:Randomized Controlled Trials as Topic; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors