Comparative virulence of intra- and interstrain lipopolysaccharide variants of Coxiella burnetii in the guinea pig model

Abstract

We compared the relative infectivity and virulence of lipopolysaccharide (LPS) variants of the Nine Mile strain of Coxiella burnetii with those of the Priscilla strain, a representative of endocarditis-type strains. In agreement with results of previous studies, Nine Mile phase I (9mi/I) organisms were highly infectious, eliciting seroconversion and fever with inocula containing as few as four organisms. Viable 9mi/I was recovered from the spleens of infected animals 30 days postinfection. Nine Mile phase II (9mi/II) organisms did not elicit fever or seroconversion except with very large inocula, and viable organisms could not be recovered at 30 days postinfection. The Nine Mile/Crazy variant, bearing the intermediate-type LPS, was also highly infectious, as determined by fever response and seroconversion, although, as with 9mi/II, viable organisms could not be recovered 30 days postinfection. The Priscilla strain in phase I (Pris/I) was as infectious as 9mi/I, as determined by seroconversion and its presence in the spleen 30 days postinfection; but in contrast to 9mi/I, more than 105 Pris/I isolates were required to induce fever. The temporal appearances of anti-phase I and II antibodies were similar for the two strains. A variety of serological techniques measuring antibody response against whole-cell and purified LPS antigens in agglutination, immunofluorescence, enzyme-linked immunosorbent, and immunoblot assays did not demonstrate sufficient specificity to distinguish between 9mi/I and Pris/I infections. Results of vaccine cross-challenge experiments showed a significant degree of protection between homologous and heterologous challenge strains.

Detecting and measuring small numbers of viableCoxiella burnetii

“…All C. burnetii isolates are not the same (Moos & Hackstadt, 1987;Kazar et al, 1993) so we decided to test 3/3 10 À6 3/3 10 À7 3/3 2/3 10 À8 1/3 0/3 10 À9 1/3 0/3 10 À10 0/3 0/3 10 À11 0/3 10 À12 0/3 DD 50 1.5 9 10 8 1.5 9 10 7 DD 50 , qPCR detection dose 50.…”

Comparative Virulence of Phase I and II Coxiella burnetii in Immunodeficient Mice

“…Comparison of biological differences of the phase variants has been studied in various ways, but a clear difference of the virulence in vivo was only found for pyrogenicity in guinea pigs 8 and may result from LPS O-side-chain differences. In this study, we showed difference of phase I and II C. burnetii virulence in pathology for the first time.…”

From neglected to dissected: How technological advances are leading the way to the study ofCoxiella burnetiipathogenesis

“…This is required to favour the autophagymediated homotypic fusion between CCVs. Although not a Cvp, Cig57 interacts with the clathrin adaptor FCHO2 at clathrin-coated pits and reroutes clathrin-mediated membrane traffic to the CCV (NMII) of the Nine Mile Phase I strain (NMI), presenting a single deletion of 21 genes involved in lipopolysaccharide biosynthesis and displaying loss-of-virulence phenotype in animal models (Moos and Hackstadt, 1987;Hoover et al, 2002). Thus, NMII was allowed for manipulation in biosafety level-2 (BSL-2) environments ( Figure 2D), as opposed to other C. burnetii strains that require manipulation in…”