Comparative Genomics and Physiology of Akkermansia muciniphila Isolates from Human Intestine Reveal Specialized Mucosal Adaptation

Akkermansia muciniphila is a champion of mucin degradation in the human gastrointestinal tract. Here, we report the isolation of six novel strains from healthy human donors and their genomic, proteomic and physiological characterization in comparison to the type-strains A. muciniphila Muc(T) and A. glycaniphila Pyt(T). Complete genome sequencing revealed that, despite their large genomic similarity (>97.6%), the novel isolates clustered into two distinct subspecies of A. muciniphila: Amuc1, which includes the type-strain Muc(T), and AmucU, a cluster of unassigned strains that have not yet been well characterized. CRISPR analysis showed all strains to be unique and confirmed that single healthy subjects can carry more than one A. muciniphila strain. Mucin degradation pathways were strongly conserved amongst all isolates, illustrating the exemplary niche adaptation of A. muciniphila to the mucin interface. This was confirmed by analysis of the predicted glycoside hydrolase profiles and supported by comparing the proteomes of A. muciniphila strain H2, belonging to the AmucU cluster, to Muc(T) and A. glycaniphila Pyt(T) (including 610 and 727 proteins, respectively). While some intrinsic resistance was observed among the A. muciniphila straind, none of these seem to pose strain-specific risks in terms of their antibiotic resistance patterns nor a significant risk for the horizontal transfer of antibiotic resistance determinants, opening the way to apply the type-strain Muc(T) or these new A. muciniphila strains as next generation beneficial microbes.

Automated summary

This study isolated six novel strains of Akkermansia muciniphila from healthy human donors and compared their genomic, proteomic, and physiological characteristics to the type strains. The isolates clustered into two distinct subspecies, with one subspecies yet to be well characterized. All strains showed unique characteristics, and it was found that single healthy individuals can carry multiple strains of A. muciniphila. The strains exhibited strong conservation in mucin degradation pathways and showed potential as beneficial microbes without significant antibiotic resistance risks.