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.
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: J Ma; T Chen; J Mandelin; A Ceponis; N E Miller; M Hukkanen; G F Ma; Y T Konttinen Journal: Cell Mol Life Sci Date: 2003-11 Impact factor: 9.261
Authors: Harlan D Caldwell; Heidi Wood; Debbie Crane; Robin Bailey; Robert B Jones; David Mabey; Ian Maclean; Zeena Mohammed; Rosanna Peeling; Christine Roshick; Julius Schachter; Anthony W Solomon; Walter E Stamm; Robert J Suchland; Lacey Taylor; Sheila K West; Tom C Quinn; Robert J Belland; Grant McClarty Journal: J Clin Invest Date: 2003-06 Impact factor: 14.808
Authors: K H Ramsey; J H Schripsema; B J Smith; Y Wang; B C Jham; K P O'Hagan; N R Thomson; A K Murthy; R J Skilton; P Chu; I N Clarke Journal: Infect Immun Date: 2014-05-27 Impact factor: 3.441
Authors: Valerie Grinblat-Huse; Elliott F Drabek; Heather Huot Creasy; Sean C Daugherty; Kristine M Jones; Ivette Santana-Cruz; Luke J Tallon; Timothy D Read; Thomas P Hatch; Patrik Bavoil; Garry S A Myers Journal: J Bacteriol Date: 2011-05-27 Impact factor: 3.490
Authors: Yanyan Qu; Lauren C Frazer; Catherine M O'Connell; Alice F Tarantal; Charles W Andrews; Shelby L O'Connor; Ali N Russell; Jeanne E Sullivan; Taylor B Poston; Abbe N Vallejo; Toni Darville Journal: Infect Immun Date: 2015-07-27 Impact factor: 3.441
Authors: Jin Wang; Tae Won Yoon; Robert Read; Ae-Kyung Yi; Robert W Williams; Elizabeth A Fitzpatrick Journal: Am J Physiol Lung Cell Mol Physiol Date: 2020-01-15 Impact factor: 5.464
Authors: Rudi Alberts; Hairong Chen; Claudia Pommerenke; August B Smit; Sabine Spijker; Robert W Williams; Robert Geffers; Dunja Bruder; Klaus Schughart Journal: BMC Genomics Date: 2011-12-19 Impact factor: 3.969
Authors: Deana K Jasper; Ira M Sigar; Justin H Schripsema; Carlyn K Sainvil; Christopher L Smith; Laxmi Yeruva; Roger G Rank; Ashlesh K Murthy; Jared R Widder; Kyle H Ramsey Journal: Pathog Dis Date: 2015-01-28 Impact factor: 3.166
Authors: Ira M Sigar; Justin H Schripsema; Yibing Wang; Ian N Clarke; Lesley T Cutcliffe; Helena M B Seth-Smith; Nicholas R Thomson; Carina Bjartling; Magnus Unemo; Kenneth Persson; Kyle H Ramsey Journal: Pathog Dis Date: 2013-09-10 Impact factor: 3.166