Identification of a Legionella Pneumophila Locus Required for Intracellular Multiplication in Human Macrophages

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Oct 15

PMID 1409673

Citations 144

Authors

A Marra

S J Blander

M A Horwitz

H A Shuman

Affiliations

Soon will be listed here.

Abstract

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.

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