title: A mutation in an ompR-like gene on a Legionella longbeachae serogroup 1 plasmid attenuates virulence.
abstract: Examination of a panel of Legionella longbeachae serogroup 1 strains using a guinea pig model of virulence determined that this clonal species of Legionella shows a remarkable variation in symptoms and disease outcome (Doyle et al., Infect. Immun. 69, 5335-5344, 2001). The presence of plasmids was investigated, as plasmid encoded functions may contribute to the virulence of genetically similar strains. Partial sequence analysis of a large native plasmid (approximately 120 kb), designated pA5H5, from a highly virulent Australian isolate revealed a putative two-component regulatory system with inferred identity to the OmpR family of two-component transcriptional regulatory proteins and EnvZ sensor kinases. An isogenic mutant was constructed in the transcriptional regulatory gene, designated lrpR (L. longbeachae sg 1 regulatory protein) and this strain was tested in Acanthamoeba, U937 cells and in a guinea pig animal model. The mutant was reduced in intracellular multiplication within Acanthamoeba but not U937 macrophage-like cells. However, the lrpR mutant did appear reduced in invasion at the early stages of infection of U937 cells. The lrpR mutant was also attenuated for virulence in a guinea pig animal model of infection. The importance of plasmid-encoded functions for the pathogenicity of Legionella longbeachae serogroup 1 strains is discussed.
authors.affiliation: Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, South Australia. robyn.doyle@imvs.sa.gov.au
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Doyle
authors.forename: Michael W
authors.initials: MW
authors.lastname: Heuzenroeder
mesh_terms: D000048:Acanthamoeba / Q000382:microbiology; D000818:Animals; D001315:Australia; D001426:Bacterial Proteins; D001483:Base Sequence; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D006168:Guinea Pigs; D006801:Humans; D007875:Legionella / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D007876:Legionellosis / Q000382:microbiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010957:Plasmids / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells / Q000382:microbiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015534:Trans-Activators; C112177:osmolarity response regulator proteins