title: Chlamydia psittaci genetic variants differ in virulence by modulation of host immunity.
abstract: BACKGROUND
  Psittacosis is a zoonosis caused by Chlamydia psittaci and is characterized by severe pneumonia and systemic infection. We sought to determine the basis of the 1000-fold difference in lethal dose of 2 C. psittaci 6BC strains in mice.
  
  
  METHODS
  Genomes of the strains were sequenced. Mice were infected intraperitoneally and the growth kinetics, immune responses, and pathology were compared.
  
  
  RESULTS
  The 2 strains differed by the presence of a 7.5-kb plasmid in the attenuated strain and 7 nonsynonomous single-nucleotide polymorphisms between the chromosomes, including a serine/threonine protein kinase gene pkn5. The plasmid was cured from the attenuated strain, but it remained nonlethal. Strains did not differ in growth kinetics in vitro or in vivo. Infection with the attenuated strain led to influx of activated macrophages with relatively minor organ damage. In contrast, the virulent strain caused an influx of nonactivated macrophages, neutrophils, and significant end organ damage. Mice infected with the virulent strain survived challenge when coinfected with either the plasmid-positive or plasmid-negative attenuated strain, indicating that an active process elicited by the attenuated strain reduces inflammation and disease.
  
  
  CONCLUSIONS
  C. psittaci modulates virulence by alteration of host immunity, which is conferred by small differences in the chromosome.
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. imiyairi@uthsc.edu
authors.forename: Isao
authors.initials: I
authors.lastname: Miyairi
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Laxton
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Obert
authors.forename: Venkat R R
authors.initials: VR
authors.lastname: Arva Tatireddigari
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Hatch
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Byrne
mesh_terms: D000818:Animals; D002691:Chlamydophila psittaci / Q000235:genetics* / Q000472:pathogenicity*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D009956:Psittacosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2