title: The CpxRA two-component system contributes to Legionella pneumophila virulence.
abstract: The bacterium Legionella pneumophila is capable of intracellular replication within freshwater protozoa as well as human macrophages, the latter of which results in the serious pneumonia Legionnaires' disease. A primary factor involved in these host cell interactions is the Dot/Icm Type IV secretion system responsible for translocating effector proteins needed to establish and maintain the bacterial replicative niche. Several regulatory factors have been identified to control the expression of the Dot/Icm system and effectors, one of which is the CpxRA two-component system, suggesting essentiality for virulence. In this study, we generated cpxR, cpxA and cpxRA in-frame null mutant strains to further delineate the role of the CpxRA system in bacterial survival and virulence. We found that cpxR is essential for intracellular replication within Acanthamoeba castellanii, but not in U937-derived macrophages. Transcriptome analysis revealed that CpxRA regulates a large number of virulence-associated proteins including Dot/Icm effectors as well as Type II secreted substrates. Furthermore, the cpxR and cpxRA mutant strains were more sodium resistant than the parental strain Lp02, and cpxRA expression reaches maximal levels during postexponential phase. Taken together, our findings suggest the CpxRA system is a key contributor to L. pneumophila virulence in protozoa via virulence factor regulation.
authors.affiliation: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Tanner
authors.affiliation: Faculty of Agricultural and Environmental Sciences, Department of Natural Resource Sciences, McGill University, Ste-Anne-de-Bellevue, QC, H9X 3V9, Canada.
authors.forename: Laam
authors.initials: L
authors.lastname: Li
authors.affiliation: Faculty of Agricultural and Environmental Sciences, Department of Natural Resource Sciences, McGill University, Ste-Anne-de-Bellevue, QC, H9X 3V9, Canada.
authors.forename: Sébastien P
authors.initials: SP
authors.lastname: Faucher
authors.affiliation: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
authors.forename: Ann Karen C
authors.initials: AK
authors.lastname: Brassinga
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D008264:Macrophages / Q000382:microbiology; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C092472:CpxA protein, bacteria