Insights into the Antimicrobial Resistance Profile of a Next Generation Probiotic Akkermansia muciniphila DSM 22959

Abstract

Akkermansia muciniphila is a Gram-negative intestinal anaerobic bacterium recently proposed as a novel probiotic candidate to be incorporated in food and pharmaceutical forms. Despite its multiple health benefits, the data addressing its antimicrobial susceptibility profile remain scarce. However, the absence of acquired resistance in probiotic strains is a compulsory criterion for its approval in the qualified presumption of safety list. This study aimed at characterizing the A. muciniphila DSM 22959 strain's antimicrobial susceptibility profile using phenotypic and in silico approaches. To establish the phenotypic antimicrobial susceptibility profile of this strain, minimum inhibitory concentrations of eight antimicrobials were determined using broth microdilution and E-test methods. Additionally, the A. muciniphila DSM 22959 genome was screened using available databases and bioinformatics tools to identify putative antimicrobial resistance genes (ARG), virulence factors (VF), genomic islands (GI), and mobile genetic elements (MGE). The same categorization was obtained for both phenotypic methods. Resistance phenotype was observed for gentamicin, kanamycin, streptomycin, and ciprofloxacin, which was supported by the genomic context. No evidence was found of horizontal acquisition or potential transferability of the identified ARG and VF. Thus, this study provides new insights regarding the phenotypic and genotypic antimicrobial susceptibility profiles of the probiotic candidate A. muciniphila DSM 22959.

Keywords: Akkermansia muciniphila; antimicrobial resistance genes; antimicrobial susceptibility testing; in silico analysis; mobile genetic elements; safety profile.

Figure 1

Akkermansia muciniphila DSM 22959 genome map. (A) represents the whole chromosome, with MGE (in orange), GI (in red) and Prophage-like region (in green), highlighted in the external circles; possible ARG, identified by CARD are represented inside the chromosome circle: in blue, ARG confirmed with PATRIC and CARD; in grey, ARG identified only by CARD; in orange, ARG identified only by PATRIC and in purple ARG encoded within a GI. (B) GI (red bars), MGE (orange bar) and prophage-like region (green bar) representation and GC content across the chromosome, with colour coded scheme, to ease the correlation. Images produced in SnapGene Viewer.