Synergistic contribution of the Legionella pneumophila lqs genes to pathogen-host interactions.
Synergistic contribution of the Legionella pneumophila lqs genes to pathogen-host interactions.
复制标题
嗜肺军团菌 lqs 基因对病原体-宿主相互作用的协同作用。
DOI：
10.1128/jb.01002-08
复制
发表时间：
2008
影响因子：
3.2
通讯作者：
Hilbi,Hubert
中科院分区：
文献类型：
--
作者：
Tiaden,Andre;Spirig,Thomas;Carranza,Paula;Bruggemann,Holger;Riedel,Kathrin;Eberl,Leo;Buchrieser,Carmen;Hilbi,Hubert
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. pneumophilaharbors thelqs(Legionella quorumsensing) 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 inEscherichia coli. LqsR promotes host-cell interactions as an element of the stationary-phase virulence regulatory network. Here, we characterizeL. pneumophilamutant strains lacking all four genes of thelqscluster or only thehdeDgene. While anhdeDmutant strain did not have overt physiological or virulence phenotypes, anlqsmutant 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 thelqsgenes into the chromosome of anlqsmutant strain. The deletion of thelqscluster caused more-severe phenotypes than deletion of onlylqsR, suggesting a synergistic effect of the otherlqsgenes. A transcriptome analysis indicated that in the stationary phase more than 380 genes were differentially regulated in thelqsmutant and wild-typeL. pneumophila. Genes involved in protein production, metabolism, and bioenergetics were upregulated in thelqsmutant, 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 thelqsgene cluster, which confirms the findings from DNA microarray assays and mirrors the virulence phenotype of thelqsmutant strain.
