Synergistic Contribution of the Legionella pneumophila lqs Genes to Pathogen-Host Interactions

被引:57
作者
Tiaden, Andre [1 ]
Spirig, Thomas [1 ]
Carranza, Paula [2 ]
Brueggemann, Holger [3 ,4 ]
Riedel, Kathrin [2 ]
Eberl, Leo [2 ]
Buchrieser, Carmen [3 ,4 ]
Hilbi, Hubert [1 ]
机构
[1] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland
[2] Univ Zurich, Inst Plant Biol, CH-8008 Zurich, Switzerland
[3] Inst Pasteur, CNRS, URA 2171, F-75724 Paris, France
[4] Inst Pasteur, Unite Biol Bacteries Intracellulaires, F-75724 Paris, France
基金
瑞士国家科学基金会;
关键词
D O I
10.1128/JB.01002-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The causative agent of Legionnaires' disease, Legionella pneumophila, is a natural parasite of environmental protozoa and employs a biphasic life style to switch between a replicative and a transmissive (virulent) phase. L. pneumophila harbors the lqs (Legionella quorum sensing) cluster, which includes genes encoding the autoinducer synthase LqsA, the sensor kinase LqsS, the response regulator LqsR, and a homologue of HdeD, which is involved in acid resistance in Escherichia coli. LqsR promotes host-cell interactions as an element of the stationary-phase virulence regulatory network. Here, we characterize L. pneumophila mutant strains lacking all four genes of the lqs cluster or only the hdeD gene. While an hdeD mutant strain did not have overt physiological or virulence phenotypes, an lqs mutant showed an aberrant morphology in stationary growth phase and was defective for intracellular growth, efficient phagocytosis, and cytotoxicity against host cells. Cytotoxicity was restored upon reintroduction of the lqs genes into the chromosome of an lqs mutant strain. The deletion of the lqs cluster caused more-severe phenotypes than deletion of only lqsR, suggesting a synergistic effect of the other lqs genes. A transcriptome analysis indicated that in the stationary phase more than 380 genes were differentially regulated in the lqs mutant and wild-type L. pneumophila. Genes involved in protein production, metabolism, and bioenergetics were upregulated in the lqs mutant, whereas genes encoding virulence factors, such as effectors secreted by the Icm/Dot type IV secretion system, were downregulated. A proteome analysis revealed that a set of Icm/Dot substrates is not produced in the absence of the lqs gene cluster, which confirms the findings from DNA microarray assays and mirrors the virulence phenotype of the lqs mutant strain.
引用
收藏
页码:7532 / 7547
页数:16
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