• Open Access

Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria

Authors

  • Anil K. Ojha,

    1. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
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  • Anthony D. Baughn,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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  • Dhinakaran Sambandan,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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  • Tsungda Hsu,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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  • Xavier Trivelli,

    1. Unité de Glycobiologie Structurale et Fonctionnelle, CNRS UMR 8576, Université des Sciences et Technologies de Lille, 59650 Villeneuve d'Ascq, Cédex, France.
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  • Yann Guerardel,

    1. Unité de Glycobiologie Structurale et Fonctionnelle, CNRS UMR 8576, Université des Sciences et Technologies de Lille, 59650 Villeneuve d'Ascq, Cédex, France.
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  • Anuradha Alahari,

    1. Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier II et I, CNRS; UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
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  • Laurent Kremer,

    1. Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier II et I, CNRS; UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
    2. INSERM, DIMNP, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
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  • William R. Jacobs Jr,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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  • Graham F. Hatfull

    1. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
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  • Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

*E-mail: gfh@pitt.edu; Tel. 412 624 4350; Fax 412 624 9311.

Summary

Successful treatment of human tuberculosis requires 6–9 months' therapy with multiple antibiotics. Incomplete clearance of tubercle bacilli frequently results in disease relapse, presumably as a result of reactivation of persistent drug-tolerant Mycobacterium tuberculosis cells, although the nature and location of these persisters are not known. In other pathogens, antibiotic tolerance is often associated with the formation of biofilms – organized communities of surface-attached cells – but physiologically and genetically defined M. tuberculosis biofilms have not been described. Here, we show that M. tuberculosis forms biofilms with specific environmental and genetic requirements distinct from those for planktonic growth, which contain an extracellular matrix rich in free mycolic acids, and harbour an important drug-tolerant population that persist despite exposure to high levels of antibiotics.

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