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Virulence factor expression patterns in Pseudomonas aeruginosa strains from infants with cystic fibrosis

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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.

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Acknowledgements

This work was supported by grants from the National Health and Medical Research Council (NHMRC, # 351541) and the Australian Cystic Fibrosis Trust. Cynthia B. Whitchurch was supported by an NHMRC Career Development Award and an NHMRC Senior Research Fellowship.

Conflict of interest

All authors declare that they have no conflict of interest.

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Author notes

  1. H. Hu

    Present address: Australian School of Advanced Medicine, Macquarie University, North Ryde, NSW, 2109, Australia

Authors and Affiliations

  1. Sydney CF Research Group, Department of Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, 2006, Australia

    J. Manos, H. Hu, B. R. Rose, C. Harmer & C. Harbour

  2. Queensland Children’s Medical Research Institute, Royal Children’s Hospital, The University of Queensland, Brisbane, Australia

    C. E. Wainwright, J. Cheney, K. Grimwood & S. N. Anuj

  3. The Kirby Institute, University of New South Wales, Darlinghurst, NSW, 2010, Australia

    I. B. Zablotska

  4. The ithree Institute, University of Technology Sydney, Sydney, NSW, 2007, Australia

    L. Turnbull & C. B. Whitchurch

  5. Department of Infectious Diseases and Immunology, University of Sydney, Blackburn Building, Sydney, NSW, 2006, Australia

    J. Manos

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Correspondence to J. Manos.

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Jim Manos and Honghua Hu contributed equally to the manuscript.

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Manos, J., Hu, H., Rose, B.R. et al. Virulence factor expression patterns in Pseudomonas aeruginosa strains from infants with cystic fibrosis. Eur J Clin Microbiol Infect Dis 32, 1583–1592 (2013). https://doi.org/10.1007/s10096-013-1916-7

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  • DOI: https://doi.org/10.1007/s10096-013-1916-7

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