Evidence of Archaeal Methanogens in Brain Abscess.

Abstract

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. 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. 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. 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.