Michel Drancourt1, Vanessa Demonfort Nkamga1, Ndèye Aïssatou Lakhe1, Jean-Marie Régis2, Henry Dufour3, Pierre-Edouard Fournier1, Yassina Bechah1, W Michael Scheld4, Didier Raoult1. 1. Unité de recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM63 CNRS 7278, IRD198, Inserm U1095. 2. Department of Stereotaxic and Functional Neurosurgery, Gamma-knife Unit, Inserm U751, Aix-Marseille University, APHM, Marseille, France. 3. Neurosurgery Department, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, Aix-Marseille Université, Marseille, France. 4. University of Virginia, Department of Medicine, Division of Infectious Diseases and International Health, Charlottesville.
Abstract
Background: Methanogens are antibiotic-resistant anaerobic archaea that escape routine detection in clinical microbiology. We hypothesized that methanogens are part of the anaerobic community that cause brain abscess. Methods: Methanogens were investigated in 1 index sample using specific polymerase chain reaction (PCR) sequencing and culture. The pathogenesis of a methanogen isolate was assessed in a mouse model. Archaea-specific quantitative (q) PCR and metagenomics were used to detect specific archaeal sequences in brain abscess samples and controls. Results: In 1 index sample, routine culture found Porphyromonas endodontalis and Streptococcus intermedius, and specific culture found Methanobrevibacter oralis susceptible to metronidazole and fusidic acid. Archaea-targeted PCR sequencing and metagenomics confirmed M. oralis along with 14 bacteria, including S. intermedius. Archaea-specific qPCR yielded archaea in 8/18 brain abscess specimens and 1/27 controls (P < .003), and metagenomics yielded archaea, mostly methanogens, in 28/32 brain abscess samples, and no archaea in 71 negative controls (P < 10-6). Infection of mice brains yielded no mortality in 14 controls and death in 17/22 M. oralis-inoculated mice (P < 10-6), 32/95 S. intermedius-inoculated mice (P < 10-6), and 75/104 mice inoculated with M. oralis mixed with S. intermedius (P < 10-6) 7 days post-inoculation. Conclusion: Methanogens belong to the anaerobic community responsible for brain abscess, and M. oralis may participate in the pathogenicity of this deadly infection. In mice, a synergy of M. oralis and S. intermedius was observed. Antibiotic treatment of brain abscess should contain anti-archaeal compounds such as imidazole derivatives in most cases.
Background: Methanogens are antibiotic-resistant anaerobic archaea that escape routine detection in clinical microbiology. We hypothesized that methanogens are part of the anaerobic community that cause brain abscess. Methods: Methanogens were investigated in 1 index sample using specific polymerase chain reaction (PCR) sequencing and culture. The pathogenesis of a methanogen isolate was assessed in a mouse model. Archaea-specific quantitative (q) PCR and metagenomics were used to detect specific archaeal sequences in brain abscess samples and controls. Results: In 1 index sample, routine culture found Porphyromonas endodontalis and Streptococcus intermedius, and specific culture found Methanobrevibacter oralis susceptible to metronidazole and fusidic acid. Archaea-targeted PCR sequencing and metagenomics confirmed M. oralis along with 14 bacteria, including S. intermedius. Archaea-specific qPCR yielded archaea in 8/18 brain abscess specimens and 1/27 controls (P < .003), and metagenomics yielded archaea, mostly methanogens, in 28/32 brain abscess samples, and no archaea in 71 negative controls (P < 10-6). Infection of mice brains yielded no mortality in 14 controls and death in 17/22 M. oralis-inoculated mice (P < 10-6), 32/95 S. intermedius-inoculated mice (P < 10-6), and 75/104 mice inoculated with M. oralis mixed with S. intermedius (P < 10-6) 7 days post-inoculation. Conclusion: Methanogens belong to the anaerobic community responsible for brain abscess, and M. oralis may participate in the pathogenicity of this deadly infection. In mice, a synergy of M. oralis and S. intermedius was observed. Antibiotic treatment of brain abscess should contain anti-archaeal compounds such as imidazole derivatives in most cases.
Authors: Kaisa Koskinen; Manuela R Pausan; Alexandra K Perras; Michael Beck; Corinna Bang; Maximilian Mora; Anke Schilhabel; Ruth Schmitz; Christine Moissl-Eichinger Journal: MBio Date: 2017-11-14 Impact factor: 7.867