C Melenotte1, A Caputo1, Y Bechah1, H Lepidi2, J Terras1, M Kowalczewska1, F Di Pinto1, C Nappez1, D Raoult3, F Brégeon4. 1. Aix Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France. 2. Aix Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France; Service d'anatomie et cytologie pathologique et de neuropathologie, CHU Timone, APHM, CHU Timone, APHM, Marseille, France. 3. Aix Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France. Electronic address: didier.raoult@gmail.com. 4. Aix Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France; Service des Explorations Fonctionnelles Respiratoires, Pôle cardio-vasculaire et thoracique, CHU Nord, APHM, chemin des Bourrely, Marseille, France.
Abstract
OBJECTIVE: Q fever epidemic outbreaks have been reported in French Guiana and in The Netherlands. To determine whether the C. burnetii strains involved in these epidemics had a peculiar virulence pattern, we compared the pathogenicity of the Guiana and the German strain (a clone of The Netherlands strain), in silico, in vitro, and in vivo versus the Nine Mile strain. METHOD: The pan-genomes of the Guiana (Cb175), German (Z3055), and the referent Nine Mile (RSA 493) C. burnetii strains were compared. In vitro, the growth rate and the morphological presentation were compared. In vivo (SCID and Balb/c mice), weight loss, histological lesions, C. burnetii bacterial load in deep organs, and serological response were reported according to each C. burnetii strain studied. RESULTS: The Guiana strain had 77 times more missing genes and 12 times more unique genes than the German strain. The Guiana strain presented as large cell variants (LCVs) and led to the most pronounced fatality rate in SCID mice (100% at 4 weeks). The German strain presented as small cell variants (SCVs), and had an intermediate fatality rate (75% at 4 weeks). Both the Guiana and the German strains led to a significant higher serological response at 2 and 4 weeks post infection (p <0.05). CONCLUSION: The Guiana strain was the most virulent strain, followed by the German strain and the referent Nine Mile strain. Unique and missing genes could be implicated but further investigations are necessary to specify their role.
OBJECTIVE: Q fever epidemic outbreaks have been reported in French Guiana and in The Netherlands. To determine whether the C. burnetii strains involved in these epidemics had a peculiar virulence pattern, we compared the pathogenicity of the Guiana and the German strain (a clone of The Netherlands strain), in silico, in vitro, and in vivo versus the Nine Mile strain. METHOD: The pan-genomes of the Guiana (Cb175), German (Z3055), and the referent Nine Mile (RSA 493) C. burnetii strains were compared. In vitro, the growth rate and the morphological presentation were compared. In vivo (SCID and Balb/c mice), weight loss, histological lesions, C. burnetii bacterial load in deep organs, and serological response were reported according to each C. burnetii strain studied. RESULTS: The Guiana strain had 77 times more missing genes and 12 times more unique genes than the German strain. The Guiana strain presented as large cell variants (LCVs) and led to the most pronounced fatality rate in SCIDmice (100% at 4 weeks). The German strain presented as small cell variants (SCVs), and had an intermediate fatality rate (75% at 4 weeks). Both the Guiana and the German strains led to a significant higher serological response at 2 and 4 weeks post infection (p <0.05). CONCLUSION: The Guiana strain was the most virulent strain, followed by the German strain and the referent Nine Mile strain. Unique and missing genes could be implicated but further investigations are necessary to specify their role.