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. 2024 Apr 3;68(4):e0145923.
doi: 10.1128/aac.01459-23. Epub 2024 Mar 5.

Inter-phylum circulation of a beta-lactamase-encoding gene: a rare but observable event

Rémi Gschwind #  1 , Marie Petitjean #  1   2 , Claudine Fournier  3   4   5 , Julie Lao  1 , Olivier Clermont  1 , Patrice Nordmann  3   4   5   6 , Alexander Mellmann  7 , Erick Denamur  1   8 , Laurent Poirel  3   4   5   6 , Etienne Ruppé  1   2
Affiliations

Inter-phylum circulation of a beta-lactamase-encoding gene: a rare but observable event

Rémi Gschwind et al. Antimicrob Agents Chemother. .

Abstract

Beta-lactamase-mediated degradation of beta-lactams is the most common mechanism of beta-lactam resistance in Gram-negative bacteria. Beta-lactamase-encoding genes can be transferred between closely related bacteria, but spontaneous inter-phylum transfers (between distantly related bacteria) have never been reported. Here, we describe an extended-spectrum beta-lactamase (ESBL)-encoding gene (blaMUN-1) shared between the Pseudomonadota and Bacteroidota phyla. An Escherichia coli strain was isolated from a patient in Münster (Germany). Its genome was sequenced. The ESBL-encoding gene (named blaMUN-1) was cloned, and the corresponding enzyme was characterized. The distribution of the gene among bacteria was investigated using the RefSeq Genomes database. The frequency and relative abundance of its closest homolog in the global microbial gene catalog (GMGC) were analyzed. The E. coli strain exhibited two distinct morphotypes. Each morphotype possessed two chromosomal copies of the blaMUN-1 gene, with one morphotype having two additional copies located on a phage-plasmid p0111. Each copy was located within a 7.6-kb genomic island associated with mobility. blaMUN-1 encoded for an extended-spectrum Ambler subclass A2 beta-lactamase with 43.0% amino acid identity to TLA-1. blaMUN-1 was found in species among the Bacteroidales order and in Sutterella wadsworthensis (Pseudomonadota). Its closest homolog in GMGC was detected frequently in human fecal samples. This is, to our knowledge, the first reported instance of inter-phylum transfer of an ESBL-encoding gene, between the Bacteroidota and Pseudomonadota phyla. Although the gene was frequently detected in the human gut, inter-phylum transfer was rare, indicating that inter-phylum barriers are effective in impeding the spread of ESBL-encoding genes, but not entirely impenetrable.

Keywords: antimicrobial resistance; beta-lactamase; horizontal gene transfer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Morphological aspects of the two types of colonies (W: white colonies and G: gray colonies) observed after streaking the strain on lysogeny broth (LB) media.
Fig 2
Fig 2
Phylogenetic tree of amino acid sequences of representative beta-lactamases found in the bacterial realm including the MUN-1 beta-lactamase (in red). Phylogenetic tree was rooted on PenA (found in the genus Burkholderia) which is distantly related from all the other beta-lactamases.
Fig 3
Fig 3
Genetic contexts showing the environment of the blaMUN-1 gene in different species. The first three lines describe the genetic contexts of each copy of the blaMUN-1 gene in the E. coli strain. Next, illustrative representatives from the RefSeq Genomes database were chosen for the following reasons: Sutterella wadsworthensis was the only other Pseudomonadota found to bear the blaMUN-1 gene; Bacteroides uniformis was the only genome in which copies of blaMUN-1 gene were found on a chromosome and on a plasmid; Phocaeicola vulgatus, Bacteroides thetaiotaomicron, Odoribacter splanchnicus, Phocaeicola massiliensis, Phocaeicola dorei, Bacteroides xylanisolvens, and Barnesiella propionica were chosen as they were the only genomes showing a genetic context that differed from the 7.6-kb genomic island. The red box delineates the 7.6-kb genomic island described in this work. The colors in the arrows correspond to the function of each gene. A nucleotide identity percentage between adjacent lines is displayed with a gray scale.
Fig 4
Fig 4
Cophenetic distance between species holding the blaMUN-1 gene based on the 16S rRNA-encoding gene. Heatmap represents the cophenetic distance between species. If no strain holding the blaMUN-1 gene from the species was found to hold a 16S rRNA-encoding gene, 16S rRNA-encoding gene was retrieved from strains that do not hold the blaMUN-1 gene (this was the case for Alistipes putredinis in gray). Gemmata sp. did not hold a blaMUN-1 gene in its genome but its 16S rRNA-encoding gene was used to root the phylogenetic tree.
Fig 5
Fig 5
Frequency of the GMGC unigene GMGC10.047_051_980.UNKNOWN (100% identity and 96.4% cover in amino acid with the blaMUN-1 gene) in unigene sub-catalogs where it is found and the associated number of mapped reads. (A) Number of samples found in each sub-catalog containing (in red) or not (in blue) the GMGC unigene GMGC10.047_051_980.UNKNOWN. (B) Boxplot representation of normalized number of reads (out of 10 million reads) mapping onto the GMGC unigene GMGC10.047_051_980.UNKNOWN in each GMGC sub-catalog where it was found. The normalization takes into account the size of the gene and the number of reads in each sample from the sub-catalogs. First, median, and third quartiles are represented in each box. Whiskers extend from the hinge to the smallest/largest value at most/no further than 1.5× inter-quartile range from the hinge. Points represent outliers.
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