Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes.

Nicole Mayer-Hamblett, Margaret Rosenfeld, Ronald L. Gibson, Bonnie W. Ramsey, Hemantha D. Kulasekara, George Z. Retsch-Bogart, Wayne J Morgan, Daniel J. Wolter, Christopher E. Pope, Laura S. Houston, Bridget R. Kulasekara, Umer Khan, Jane L. Burns, Samuel I. Miller, Lucas R. Hoffman

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Abstract

Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease. To characterize the relationships between in vitro P. aeruginosa phenotypes, infection stage, and clinical outcomes. A total of 649 children with CF and newly identified P. aeruginosa were followed for a median 5.4 years during which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro bacterial phenotypes were assessed among the isolates, including measures of motility, exoproduct production, colony morphology, growth, and metabolism. P. aeruginosa phenotypes present at the time of culture were associated with both stage of infection (new onset, intermittent, or chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best distinguished infection stages: pyoverdine production (31% of new-onset cultures, 48% of intermittent, 69% of chronic) and reduced protease production (31%, 39%, and 65%, respectively). The best P. aeruginosa phenotypic predictors of subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95% confidence interval, 1.19-2.57) and reduced twitching motility (odds ratio, 1.43; 95% confidence interval, 1.11-1.84). In this large epidemiologic study of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro phenotypes that best distinguished early and later infection stages. Among the many phenotypes tested, mucoidy and reduced twitching best predicted subsequent PE. These phenotypes indicate potentially useful prognostic markers of transition to chronic infection and advancing lung disease.

Original languageEnglish (US)
Pages (from-to)289-297
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume190
Issue number3
StatePublished - 2014

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Cystic Fibrosis
Pseudomonas aeruginosa
Phenotype
Infection
Lung
Odds Ratio
Confidence Intervals
In Vitro Techniques
Lung Diseases
Epidemiologic Studies
Peptide Hydrolases
Growth

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Mayer-Hamblett, N., Rosenfeld, M., Gibson, R. L., Ramsey, B. W., Kulasekara, H. D., Retsch-Bogart, G. Z., ... Hoffman, L. R. (2014). Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes. American Journal of Respiratory and Critical Care Medicine, 190(3), 289-297.

Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes. / Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Gibson, Ronald L.; Ramsey, Bonnie W.; Kulasekara, Hemantha D.; Retsch-Bogart, George Z.; Morgan, Wayne J; Wolter, Daniel J.; Pope, Christopher E.; Houston, Laura S.; Kulasekara, Bridget R.; Khan, Umer; Burns, Jane L.; Miller, Samuel I.; Hoffman, Lucas R.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 190, No. 3, 2014, p. 289-297.

Research output: Contribution to journalArticle

Mayer-Hamblett, N, Rosenfeld, M, Gibson, RL, Ramsey, BW, Kulasekara, HD, Retsch-Bogart, GZ, Morgan, WJ, Wolter, DJ, Pope, CE, Houston, LS, Kulasekara, BR, Khan, U, Burns, JL, Miller, SI & Hoffman, LR 2014, 'Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes.', American Journal of Respiratory and Critical Care Medicine, vol. 190, no. 3, pp. 289-297.
Mayer-Hamblett N, Rosenfeld M, Gibson RL, Ramsey BW, Kulasekara HD, Retsch-Bogart GZ et al. Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes. American Journal of Respiratory and Critical Care Medicine. 2014;190(3):289-297.
Mayer-Hamblett, Nicole ; Rosenfeld, Margaret ; Gibson, Ronald L. ; Ramsey, Bonnie W. ; Kulasekara, Hemantha D. ; Retsch-Bogart, George Z. ; Morgan, Wayne J ; Wolter, Daniel J. ; Pope, Christopher E. ; Houston, Laura S. ; Kulasekara, Bridget R. ; Khan, Umer ; Burns, Jane L. ; Miller, Samuel I. ; Hoffman, Lucas R. / Pseudomonas aeruginosa in vitro phenotypes distinguish cystic fibrosis infection stages and outcomes. In: American Journal of Respiratory and Critical Care Medicine. 2014 ; Vol. 190, No. 3. pp. 289-297.
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abstract = "Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease. To characterize the relationships between in vitro P. aeruginosa phenotypes, infection stage, and clinical outcomes. A total of 649 children with CF and newly identified P. aeruginosa were followed for a median 5.4 years during which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro bacterial phenotypes were assessed among the isolates, including measures of motility, exoproduct production, colony morphology, growth, and metabolism. P. aeruginosa phenotypes present at the time of culture were associated with both stage of infection (new onset, intermittent, or chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best distinguished infection stages: pyoverdine production (31{\%} of new-onset cultures, 48{\%} of intermittent, 69{\%} of chronic) and reduced protease production (31{\%}, 39{\%}, and 65{\%}, respectively). The best P. aeruginosa phenotypic predictors of subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95{\%} confidence interval, 1.19-2.57) and reduced twitching motility (odds ratio, 1.43; 95{\%} confidence interval, 1.11-1.84). In this large epidemiologic study of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro phenotypes that best distinguished early and later infection stages. Among the many phenotypes tested, mucoidy and reduced twitching best predicted subsequent PE. These phenotypes indicate potentially useful prognostic markers of transition to chronic infection and advancing lung disease.",
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AU - Hoffman, Lucas R.

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