Genetic mechanisms of phase variation in Coxiella burnetii, the etiological agent of Q fever, are not known. However, various strains with different virulence factors and lipopolysaccharide structure were studied to obtain possible molecular correlates of phase transition. A. Genetic heterogeneity. Chromosomal and plasmid DNA have been extracted from six isolates of C. burnetii. Restriction fragment length polymorphisms (RFLP) detected after Hae III digestions of DNA revealed four different patterns that distinguished American from the European isolates. RFLPs were also observed between the Nine Mile phase I and phase II prototype strains. At least one of the Hae III fragments visible in the pattern from Nine Mile phase I and missing in that from Nine Mile phase II could not be detected by DNA-DNA hybridization, and thus may have been deleted during the phase transition. Strains from two human endocarditis cases showed the greatest divergence. There were at least five fragments of unique mobility in the Hae III digestion pattern of DNA from the endocarditis isolates. Also, the plasmid obtained from these two isolates was two to three kilobases larger than the plasmid present in the other five isolates. B. Lipopolysaccharide (LPS). Phase variation in LPS structure from smooth (S) to rough (R) correlates with a shift from virulent (phase I) to avirulent (phase II) C. burnetii. The S and R LPSs were different in chemical composition and microheterogeneity. LPSs studied with the electron microscope were ribbon-like or they exhibited hexagonal lattice structures. The hexagonal lattice structures formed in vitro were due to the interaction of LPS II and the staining reagents rather than protein-LPS interactions. Significance: Detection of chromosomal and plasmid RFLPs and variation in LPS structure among strains of C. burnetii from various geographic locations and environmental sources will facilitate Q fever diagnosis and strain identification.
