The antimicrobial resistance pattern of cultured human methanogens reflects the unique phylogenetic position of archaea

Objectives: Methanogenic archaea are constant members of the human oral and digestive microbiota retrieved, in particular, from periodontitis lesions. The objective of the study was to determine their susceptibility to antimicrobials. Methods: Using the macrodilution method in Hungate tubes with optical microscope observation combined with monitoring methane production, we determined the antibiotic resistance characteristics of eight methanogenic archaea. Results: Methanobrevibacter smithii strains were resistant to ampicillin, streptomycin, gentamicin, rifampicin, ofloxacin, tetracycline and amphotericin B, with MICs >= 100 mg/L; these strains were also highly resistant to vancomycin (MIC >= 50 mg/L). They were moderately resistant to chloramphenicol (MIC <= 25 mg/L), and were susceptible to bacitracin (MIC <= 4 mg/L), metronidazole, ornidazole and squalamine (MIC <= 1 mg/L). The susceptibility of Methanosphaera stadtmanae was the same as M. smithii, except for chloramphenicol (MIC <= 4 mg/L), and Methanobrevibacter oralis yielded the same data as M. smithii, except for bacitracin (MIC <= 25 mg/L). The antibiotic susceptibility pattern of 'Methanomassiliicoccus luminyensis', which was recently isolated from human faeces, was identical to that of M. smithii. Conclusions: Human methanogenic archaea are highly resistant to antibiotics, being susceptible only to molecules that are also effective against both bacteria and eukarya. Methanogenic archaea are good candidates to test for antimicrobial activity against members of this unique domain of life. Further studies to develop new molecules specifically targeting archaea as potential causes of infection are warranted.