Affiliation:
1. Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611
Abstract
ABSTRACT
Legionella pneumophila
, the agent of Legionnaires' disease, is an intracellular parasite of aquatic amoebae and human macrophages. A key factor for
L. pneumophila
in intracellular infection is its type II protein secretion system (Lsp). In order to more completely define Lsp output, we recently performed a proteomic analysis of culture supernatants. Based upon the predictions of that analysis, we found that
L. pneumophila
secretes two distinct aminopeptidase activities encoded by the genes
lapA
and
lapB
. Whereas
lapA
conferred activity against leucine, phenylalanine, and tyrosine aminopeptides,
lapB
was linked to the cleavage of lysine- and arginine-containing substrates. To assess the role of secreted aminopeptidases in intracellular infection, we examined the relative abilities of
lapA
and
lapB
mutants to infect human U937 cell macrophages as well as
Hartmannella vermiformis
and
Acanthamoeba castellanii
amoebae. Although these experiments identified a dispensable role for LapA and LapB, they uncovered a previously unrecognized role for the type II-dependent ProA (MspA) metalloprotease. Whereas
proA
mutants were not defective for macrophage or
A. castellanii
infection, they (but not their complemented derivatives) were impaired for growth upon coculture with
H. vermiformis
. Thus, ProA represents the first type II effector implicated in an intracellular infection event. Furthermore,
proA
represents an
L. pneumophila
gene that shows differential importance among protozoan infection models, suggesting that the legionellae might have evolved some of its factors to especially target certain of their protozoan hosts.
Publisher
American Society for Microbiology
Subject
Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology
Cited by
61 articles.
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