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Article
Nature Cell Biology  5, 793 - 802 (2003)
Published online: 24 August 2003; | doi:10.1038/ncb1036

Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria

Elsa Anes1, 2, 3, Mark Philipp Kühnel2, 3, Evelyne Bos2, 3, Jose Moniz-Pereira1, Anja Habermann2 & Gareth Griffiths2

1  Molecular Pathogenesis Centre, Faculty of Pharmacy, University of Lisbon, Av. Forcas Armadas, 1600-085 Lisbon, Portugal.

2  EMBL, Postfach 102209, 69117 Heidelberg, Germany.

3  These authors contributed equally to the work.

Correspondence should be addressed to Gareth Griffiths griffiths@embl.de
Pathogenic mycobacteria such as Mycobacterium tuberculosis and Mycobacterium avium facilitate disease by surviving intracellularly within a potentially hostile environment: the macrophage phagosome. They inhibit phagosome maturation processes, including fusion with lysosomes, acidification and, as shown here, membrane actin assembly. An in vitro assay developed for latex bead phagosomes (LBPs) provided insights into membrane signalling events that regulate phagosome actin assembly, a process linked to membrane fusion. Different lipids were found to stimulate or inhibit actin assembly by LBPs and mycobacterial phagosomes in vitro. In addition, selected lipids activated actin assembly and phagosome maturation in infected macrophages, resulting in a significant killing of M. tuberculosis and M. avium. In contrast, the polyunsaturated sigma-3 lipids behaved differently and stimulated pathogen growth. Thus, lipids can be involved in both stimulatory and inhibitory signalling networks in the phagosomal membrane.

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Nature Cell Biology
ISSN: 1465-7392
EISSN: 1476-4679
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