Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants.

Oana Ciofu; Baoleri Lee; Marie Johannesson; Nils Olav Hermansen; Peter Meyer; Niels Høiby; Scandinavian Cystic Fibrosis Study Consortium

doi:10.1099/mic.0.2007/010421-0

Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants.

Oana Ciofu, Baoleri Lee, Marie Johannesson, Nils Olav Hermansen, Peter Meyer, Niels Høiby, Scandinavian Cystic Fibrosis Study Consortium

Department of Immunology and Microbiology

62 Citations (Scopus)

Abstract

Pseudomonas aeruginosa is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of P. aeruginosa from the non-mucoid to the mucoid, alginate-overproducing phenotype. During the chronic infection the isolation of both mucoid and non-mucoid isolates in CF sputum samples is very common. The purpose of the present study was to establish, by sequence analysis, the types of mutations present in the algTmucABD operon in a large number of mucoid and non-mucoid P. aeruginosa isolates from Scandinavian CF patients and in in vitro-derived non-mucoid revertants. Mucoid (83) and non-mucoid isolates (103) from 91 Scandinavian patients with chronic P. aeruginosa infection and 24 non-mucoid isolates from intermittently colonized CF patients were investigated. In addition, 88 spontaneous non-mucoid revertants obtained in vitro from nine mucoid CF isolates were also included in the study. Mutations in mucA were found in 92 % of the mucoid and in up to 70 % of the non-mucoid isolates from chronically infected patients, indicating that the majority of non-mucoid isolates are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in algT. In contrast, 83 % of the in vitro-derived spontaneous non-mucoid revertants had mutations in algT, showing that in the CF lung there is a selection for non-mucoid revertants with secondary-site mutations in genes other than algT. In addition, we report, to our knowledge for the first time, loss-of-function mutations in the negative regulators mucB and mucD in CF clinical isolates. In some of the CF isolates these mutations are associated with moderate alginate production. In conclusion, most non-mucoid isolates from chronically infected CF patients are revertants and the mechanism of revertance is algT-independent in the CF lung.

Original language	English
Journal	Microbiology
Volume	154
Issue number	Pt 1
Pages (from-to)	103-13
Number of pages	10
ISSN	1350-0872
DOIs	https://doi.org/10.1099/mic.0.2007/010421-0
Publication status	Published - 2008

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Ciofu, O., Lee, B., Johannesson, M., Hermansen, N. O., Meyer, P., Høiby, N., & Scandinavian Cystic Fibrosis Study Consortium (2008). Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants. Microbiology, 154(Pt 1), 103-13. https://doi.org/10.1099/mic.0.2007/010421-0

Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants. / Ciofu, Oana; Lee, Baoleri; Johannesson, Marie et al.

In: Microbiology, Vol. 154, No. Pt 1, 2008, p. 103-13.

Research output: Contribution to journal › Journal article › Research › peer-review

Ciofu, O, Lee, B, Johannesson, M, Hermansen, NO, Meyer, P, Høiby, N & Scandinavian Cystic Fibrosis Study Consortium 2008, 'Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants.', Microbiology, vol. 154, no. Pt 1, pp. 103-13. https://doi.org/10.1099/mic.0.2007/010421-0

@article{3438a430ba2011ddae57000ea68e967b,

title = "Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants.",

abstract = "Pseudomonas aeruginosa is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of P. aeruginosa from the non-mucoid to the mucoid, alginate-overproducing phenotype. During the chronic infection the isolation of both mucoid and non-mucoid isolates in CF sputum samples is very common. The purpose of the present study was to establish, by sequence analysis, the types of mutations present in the algTmucABD operon in a large number of mucoid and non-mucoid P. aeruginosa isolates from Scandinavian CF patients and in in vitro-derived non-mucoid revertants. Mucoid (83) and non-mucoid isolates (103) from 91 Scandinavian patients with chronic P. aeruginosa infection and 24 non-mucoid isolates from intermittently colonized CF patients were investigated. In addition, 88 spontaneous non-mucoid revertants obtained in vitro from nine mucoid CF isolates were also included in the study. Mutations in mucA were found in 92 % of the mucoid and in up to 70 % of the non-mucoid isolates from chronically infected patients, indicating that the majority of non-mucoid isolates are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in algT. In contrast, 83 % of the in vitro-derived spontaneous non-mucoid revertants had mutations in algT, showing that in the CF lung there is a selection for non-mucoid revertants with secondary-site mutations in genes other than algT. In addition, we report, to our knowledge for the first time, loss-of-function mutations in the negative regulators mucB and mucD in CF clinical isolates. In some of the CF isolates these mutations are associated with moderate alginate production. In conclusion, most non-mucoid isolates from chronically infected CF patients are revertants and the mechanism of revertance is algT-independent in the CF lung.",

author = "Oana Ciofu and Baoleri Lee and Marie Johannesson and Hermansen, {Nils Olav} and Peter Meyer and Niels H{\o}iby and {Scandinavian Cystic Fibrosis Study Consortium}",

note = "Keywords: Alginates; Bacterial Proteins; Cystic Fibrosis; DNA Mutational Analysis; DNA, Bacterial; Glucuronic Acid; Hexuronic Acids; Humans; Mutation; Operon; Pseudomonas Infections; Pseudomonas aeruginosa; Sequence Analysis, DNA; Serine Endopeptidases; Sigma Factor; Sweden",

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T1 - Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants.

AU - Ciofu, Oana

AU - Lee, Baoleri

AU - Johannesson, Marie

AU - Hermansen, Nils Olav

AU - Meyer, Peter

AU - Høiby, Niels

AU - Scandinavian Cystic Fibrosis Study Consortium

N1 - Keywords: Alginates; Bacterial Proteins; Cystic Fibrosis; DNA Mutational Analysis; DNA, Bacterial; Glucuronic Acid; Hexuronic Acids; Humans; Mutation; Operon; Pseudomonas Infections; Pseudomonas aeruginosa; Sequence Analysis, DNA; Serine Endopeptidases; Sigma Factor; Sweden

PY - 2008

Y1 - 2008

N2 - Pseudomonas aeruginosa is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of P. aeruginosa from the non-mucoid to the mucoid, alginate-overproducing phenotype. During the chronic infection the isolation of both mucoid and non-mucoid isolates in CF sputum samples is very common. The purpose of the present study was to establish, by sequence analysis, the types of mutations present in the algTmucABD operon in a large number of mucoid and non-mucoid P. aeruginosa isolates from Scandinavian CF patients and in in vitro-derived non-mucoid revertants. Mucoid (83) and non-mucoid isolates (103) from 91 Scandinavian patients with chronic P. aeruginosa infection and 24 non-mucoid isolates from intermittently colonized CF patients were investigated. In addition, 88 spontaneous non-mucoid revertants obtained in vitro from nine mucoid CF isolates were also included in the study. Mutations in mucA were found in 92 % of the mucoid and in up to 70 % of the non-mucoid isolates from chronically infected patients, indicating that the majority of non-mucoid isolates are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in algT. In contrast, 83 % of the in vitro-derived spontaneous non-mucoid revertants had mutations in algT, showing that in the CF lung there is a selection for non-mucoid revertants with secondary-site mutations in genes other than algT. In addition, we report, to our knowledge for the first time, loss-of-function mutations in the negative regulators mucB and mucD in CF clinical isolates. In some of the CF isolates these mutations are associated with moderate alginate production. In conclusion, most non-mucoid isolates from chronically infected CF patients are revertants and the mechanism of revertance is algT-independent in the CF lung.

AB - Pseudomonas aeruginosa is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of P. aeruginosa from the non-mucoid to the mucoid, alginate-overproducing phenotype. During the chronic infection the isolation of both mucoid and non-mucoid isolates in CF sputum samples is very common. The purpose of the present study was to establish, by sequence analysis, the types of mutations present in the algTmucABD operon in a large number of mucoid and non-mucoid P. aeruginosa isolates from Scandinavian CF patients and in in vitro-derived non-mucoid revertants. Mucoid (83) and non-mucoid isolates (103) from 91 Scandinavian patients with chronic P. aeruginosa infection and 24 non-mucoid isolates from intermittently colonized CF patients were investigated. In addition, 88 spontaneous non-mucoid revertants obtained in vitro from nine mucoid CF isolates were also included in the study. Mutations in mucA were found in 92 % of the mucoid and in up to 70 % of the non-mucoid isolates from chronically infected patients, indicating that the majority of non-mucoid isolates are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in algT. In contrast, 83 % of the in vitro-derived spontaneous non-mucoid revertants had mutations in algT, showing that in the CF lung there is a selection for non-mucoid revertants with secondary-site mutations in genes other than algT. In addition, we report, to our knowledge for the first time, loss-of-function mutations in the negative regulators mucB and mucD in CF clinical isolates. In some of the CF isolates these mutations are associated with moderate alginate production. In conclusion, most non-mucoid isolates from chronically infected CF patients are revertants and the mechanism of revertance is algT-independent in the CF lung.

U2 - 10.1099/mic.0.2007/010421-0

DO - 10.1099/mic.0.2007/010421-0

M3 - Journal article

C2 - 18174130

SN - 1350-0872

VL - 154

SP - 103

EP - 113

JO - Microbiology

JF - Microbiology

IS - Pt 1

ER -

Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants.

Abstract

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