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

Abstract

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 MucT and A. glycaniphila PytT. 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 MucT, 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 MucT and A. glycaniphila PytT (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 MucT or these new A. muciniphila strains as next generation beneficial microbes.

Characterization of antibiotic-resistance traits in Akkermansia muciniphila strains of human origin

“…Their results showed that DSM 22959 T is resistant to gentamicin, kanamycin, streptomycin, and ciprofloxacin, consistently with our findings. Furthermore, we found our results in line with the EFSA 2021 document 20 and Ouwerkerk et al 45 , where authors reported that A. muciniphila BAA-835 (= DSM 22959 T ) presented high resistance levels to aminoglycosides, and ciprofloxacin similarly to other A. muciniphila strains.…”

Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases

“…Meanwhile, analysis of the genome sequences indicated that A. muciniphila DSM 22959 posed little risk of ARG horizontal transfer because there is no mobile genetic elements detected within its genome. Similar results were reported for the type-strain Muc T and human isolates of A. muciniphila, intrinsic resistance genes observed seem to pose no risks by determining their antibiotic resistance phenotype, and there is no significant risk for the horizontal transfer of ARGs (Ouwerkerk et al, 2022). These results indicated the ARGs of A. muciniphila might pose a small risk of transmission.…”

Analysis of gut microbiota in patients with Williams–Beuren Syndrome reveals dysbiosis linked to clinical manifestations

“…On the other hand, we observed a decrease of short chain fatty acids (SCFAs) producers, like Anaerostipes, Ruminococcus, Blautia, Coprococcus , Bifidobacterium, Barnesiella and Akkermansia 30 – 32 . These bacteria have anti-inflammatory properties and their decrease could contribute to functional dysbiosis.…”