Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages.

AUTOR(ES)

Marra, A

RESUMO

The legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular parasite. Its interaction with phagocytes has characteristics in common with several other intracellular parasites. Critical aspects of L. pneumophila intracellular multiplication are evasion of lysosomal host cell defenses and the presence of a nutritionally appropriate environment. Following phagocytosis, wild-type L. pneumophila multiply within a specialized phagosome which does not fuse with secondary lysosomes. Mutants which have lost the ability to grow within phagocytes no longer cause disease in animals, indicating that the capacity to multiply intracellularly is important for pathogenesis. One such mutant, 25D, has been shown to be defective in inhibiting phagosome-lysosome fusion. This phagolysosomal environment is not conducive to Legionella growth. We report the isolation of a region of the L. pneumophila genome (icm, intracellular multiplication) which restores the capacity of 25D to multiply in human macrophages. The complemented mutants also regain the capacity to interfere with phagosome-lysosome fusion and to cause lethal pneumonia in guinea pigs.

Documentos Relacionados

• Identification of Legionella pneumophila genes required for growth within and killing of human macrophages.
• 2-Deoxy-D-glucose inhibits intracellular multiplication and promotes intracellular killing of Legionella pneumophila in A/J mouse macrophages.
• Legionella pneumophila mip gene potentiates intracellular infection of protozoa and human macrophages.
• Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages.
• Intracellular multiplication of Legionella pneumophila in cultured human embryonic lung fibroblasts.