Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection

Manu Jain*, Maskit Bar-Meir, Susanna A McColley, Joanne Cullina, Eileen Potter, Cathy Powers, Michelle Prickett, Roopa Seshadri, Borko Jovanovic, Argyri Petrocheilou, John D. King, Alan R Hauser

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Pseudomonas aeruginosa (PA) from acute and chronic (eg, cystic fibrosis [CF]) infections differ in several respects, but they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and to examine its role in clinical outcomes. A total of 114 CF subjects were divided into 3 cohorts: 1st infected individuals, CI children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were collected prospectively. In 1st infection, 45.2% ± 9.1% of PA isolates secreted T3 proteins compared with 29.1% ± 4.2% and 11.5% ± 3.0% in CI children and CI adults, respectively (P < 0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r = -0.32, P < 0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inversely correlated with the forced expiratory volume in 1 s (FEV1) decline (r = -0.35, P = 0.02). In 1st infection, 82% of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P < 0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV1 decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalTranslational Research
Volume152
Issue number6
DOIs
StatePublished - Jan 1 2008

Fingerprint

Cystic Fibrosis
Pseudomonas aeruginosa
Virulence Factors
Infection
Proteins
Forced Expiratory Volume
Pseudomonas Infections
Lung
Spirometry
Phenotype

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical

Cite this

Jain, Manu ; Bar-Meir, Maskit ; McColley, Susanna A ; Cullina, Joanne ; Potter, Eileen ; Powers, Cathy ; Prickett, Michelle ; Seshadri, Roopa ; Jovanovic, Borko ; Petrocheilou, Argyri ; King, John D. ; Hauser, Alan R. / Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis : a paradigm of chronic infection. In: Translational Research. 2008 ; Vol. 152, No. 6. pp. 257-264.
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abstract = "Pseudomonas aeruginosa (PA) from acute and chronic (eg, cystic fibrosis [CF]) infections differ in several respects, but they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and to examine its role in clinical outcomes. A total of 114 CF subjects were divided into 3 cohorts: 1st infected individuals, CI children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were collected prospectively. In 1st infection, 45.2{\%} ± 9.1{\%} of PA isolates secreted T3 proteins compared with 29.1{\%} ± 4.2{\%} and 11.5{\%} ± 3.0{\%} in CI children and CI adults, respectively (P < 0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r = -0.32, P < 0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inversely correlated with the forced expiratory volume in 1 s (FEV1) decline (r = -0.35, P = 0.02). In 1st infection, 82{\%} of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P < 0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV1 decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection.",
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Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis : a paradigm of chronic infection. / Jain, Manu; Bar-Meir, Maskit; McColley, Susanna A; Cullina, Joanne; Potter, Eileen; Powers, Cathy; Prickett, Michelle; Seshadri, Roopa; Jovanovic, Borko; Petrocheilou, Argyri; King, John D.; Hauser, Alan R.

In: Translational Research, Vol. 152, No. 6, 01.01.2008, p. 257-264.

Research output: Contribution to journalArticle

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T1 - Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis

T2 - a paradigm of chronic infection

AU - Jain, Manu

AU - Bar-Meir, Maskit

AU - McColley, Susanna A

AU - Cullina, Joanne

AU - Potter, Eileen

AU - Powers, Cathy

AU - Prickett, Michelle

AU - Seshadri, Roopa

AU - Jovanovic, Borko

AU - Petrocheilou, Argyri

AU - King, John D.

AU - Hauser, Alan R

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AB - Pseudomonas aeruginosa (PA) from acute and chronic (eg, cystic fibrosis [CF]) infections differ in several respects, but they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and to examine its role in clinical outcomes. A total of 114 CF subjects were divided into 3 cohorts: 1st infected individuals, CI children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were collected prospectively. In 1st infection, 45.2% ± 9.1% of PA isolates secreted T3 proteins compared with 29.1% ± 4.2% and 11.5% ± 3.0% in CI children and CI adults, respectively (P < 0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r = -0.32, P < 0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inversely correlated with the forced expiratory volume in 1 s (FEV1) decline (r = -0.35, P = 0.02). In 1st infection, 82% of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P < 0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV1 decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection.

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