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Intraclonal diversity of the Pseudomonas aeruginosa cystic fibrosis airway isolates TBCF10839 and TBCF121838: distinct signatures of transcriptome, proteome, metabolome, adherence and pathogenicity despite an almost identical genome sequence

Authors

  • Jens Klockgether,

    Corresponding author
    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, D-30625 Hannover, Germany.
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  • Norbert Miethke,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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    • Present addresses: HNO-Praxis, D-49740 Haselünne, Germany;

  • Peter Kubesch,

    1. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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    • Burgdorf Medical GmbH, D-31303 Burgdorf, Germany;

  • Yu-Sing Bohn,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
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  • Inka Brockhausen,

    1. Department of Medicine, Queen's University, Kingston, ON K7L 3N6, Canada.
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  • Nina Cramer,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, D-30625 Hannover, Germany.
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  • Leo Eberl,

    1. Institut für Pflanzenbiologie, Universität Zürich, CH-8008 Zürich, Switzerland.
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  • Joachim Greipel,

    1. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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  • Christian Herrmann,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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    • Klinikum Region Hannover, D-30655 Hannover, Germany;

  • Susanne Herrmann,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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    • Klinikum Region Hannover, D-30655 Hannover, Germany;

  • Sonja Horatzek,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
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    • Helmholtz Institut für Infektionsforschung, D-38124 Braunschweig, Germany;

  • Meike Lingner,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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    • Gesundheitszentrum, D-38100 Braunschweig, Germany;

  • Liliana Luciano,

    1. Institut für Zellbiologie im Zentrum Anatomie, OE 4130, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
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  • Prabhakar Salunkhe,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
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    • Amrita Therapeutics Limited, Thaltej, Ahmedabad-380 054, India;

  • Dietmar Schomburg,

    1. Institut für Biochemie & Biotechnologie, Technische Universität Braunschweig, D-38106 Braunschweig, Germany.
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  • Maria Wehsling,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Institut für Biophysikalische Chemie, OE 4350, D-30625 Hannover, Germany.
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    • Merck KGaA, D-64293 Darmstadt, Germany.

  • Lutz Wiehlmann,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, D-30625 Hannover, Germany.
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  • Colin F. Davenport,

    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, D-30625 Hannover, Germany.
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  • Burkhard Tümmler

    Corresponding author
    1. Klinische Forschergruppe, Zentrum Biochemie und Zentrum Kinder- und Jugendmedizin, OE 6710, D-30625 Hannover, Germany.
    2. Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, OE 6710, D-30625 Hannover, Germany.
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E-mail klockgether.jens@mh-hannover.de; tuemmler.burkhard@mh-hannover.de; Tel. (+49) 511 5328733; Fax (+49) 511 4326723.

Summary

Microevolution of closely related Pseudomonas aeruginosa was compared in the clone TB strains TBCF10839 and TBCF121838 which had been isolated from two unrelated individuals with cystic fibrosis who had acquired clone TB during a local outbreak. Compared with the strain PAO1 reference sequence the two clone TB genomes shared 23 155 nucleotide exchanges, 32 out-of-frame indels in the coding region and another repertoire of replacement and genomic islands such as PAGI-1, PAGI-2, PAGI-5, LESGI-1 and LES-prophage 4. Only TBCF121838 carried a genomic island known from Ralstonia pickettii. Six of the seven strain-specific sequence variations in the core genome were detected in genes affecting motility, biofilm formation or virulence, i.e. non-synonymous nucleotide substitutions in mexS, PA3729, PA5017, mifR, a frameshift mutation in pilF (TBCF121838) and an intragenic deletion in pilQ (TBCF10839). Despite their almost identical genome sequence the two strains differed strongly from each other in transcriptome and metabolome profiles, mucin adherence and phagocytosis assays. TBCF121838 was susceptible to killing by neutrophils, but TBCF10839 could grow in leucocytes. Microevolution in P. aeruginosa apparently can generate novel complex traits by few or even single mutations provided that predisposing mutational events had occurred before in the clonal lineage.

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