The functions of OmpATb, a pore-forming protein of Mycobacterium tuberculosis

Authors

  • Catherine Raynaud,

    1. The Division of Mycobacterial Research, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
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  • K. G. Papavinasasundaram,

    1. The Division of Mycobacterial Research, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
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  • Richard A. Speight,

    1. The Division of Mycobacterial Research, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
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    • Present address: GeneWorks Pty Ltd, PO Box 11, Rundle Mall, South Australia 5000.

  • Burkhard Springer,

    1. Institut für Medizinische Mikrobiologie, Universität Zurich, Gloriastrasse 30/32, 8028 Zurich, Switzerland.
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  • Peter Sander,

    1. Institut für Medizinische Mikrobiologie, Universität Zurich, Gloriastrasse 30/32, 8028 Zurich, Switzerland.
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  • Erik C. Böttger,

    1. Institut für Medizinische Mikrobiologie, Universität Zurich, Gloriastrasse 30/32, 8028 Zurich, Switzerland.
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  • M. Joseph Colston,

    Corresponding author
    1. The Division of Mycobacterial Research, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
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  • Philip Draper

    1. The Division of Mycobacterial Research, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
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Summary

The functions of OmpATb, the product of the ompATb gene of Mycobacterium tuberculosis and a putative porin, were investigated by studying a mutant with a targeted deletion of the gene, and by observing expression of the gene in wild-type M. tuberculosis H37Rv by real-time polymerase chain reaction (PCR) and immunoblotting. The loss of ompATb had no effect on growth under normal conditions, but caused a major reduction in ability to grow at reduced pH. The gene was substantially upregulated in wild-type bacteria exposed to these conditions. The mutant was impaired in its ability to grow in macrophages and in normal mice, although it was as virulent as the wild type in mice that lack T cells. Deletion of the ompATb gene reduced permeability to several small water-soluble substances. This was particularly evident at pH 5.5; at this pH, uptake of serine was minimal, suggesting that, at this pH, OmpATb might be the only functioning porin. These data indicate that OmpATb has two functions: as a pore-forming protein with properties of a porin, and in enabling M. tuberculosis to respond to reduced environmental pH. It is not known whether this second function is related to the porin-like activity at low pH or involves a completely separate role for OmpATB. The involvement with pH is likely to contribute to the ability of M. tuberculosis to overcome host defence mechanisms and grow in a mammalian host.

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