Genetic insights into Shewanella spp., progenitor of the bla OXA-48-like genes: a large-scale study

Abstract

Shewanella spp. played pivotal ecological roles and were reported to be the progenitor of bla _OXA-48-like carbapenemase genes. However, it remained unknown which species was the progenitor of different OXA-48 carbapenemase variants. To address this issue, we analysed the largest collection of Shewanella genomes to our knowledge and performed genetic and phenotypic analysis on Shewanella collected from Zhejiang province, China. Our results suggested that bla _OXA-48-like was intrinsically carried by a few Shewanella species and different bla _OXA-48-like variants were associated with different Shewanella species; for instance, Shewanella baltica was associated with bla _OXA-924, and some Shewanella oncorhynchi and Shewanella putrefaciens carried bla _OXA-900-like. The bla _OXA-48-like genes carried by Shewanella xiamenensis were highly diverse. Comparatively, none of the Shewanella algae genomes carried bla _OXA-48-like. Results of phylogenetic analysis supported the notion that OXA-48-like carbapenemase originated from different environmental Shewanella species and was captured by clinical species, particularly Enterobacterales. Different Shewanella species distributed in different niches in Zhejiang province, i.e. S. algae (n=12) and Shewanella indica (n=1) strains were all isolated from clinical settings and S. xiamenensis (n=23) and Shewanella mangrovisoli (n=2) were isolated from both hospital sewage and river water. bla _OXA-48-like genes in Shewanella spp. from Zhejiang province were located on the chromosome. To the best of our knowledge, this is the first study investigating the progenitor of different bla _OXA-48-like variants with a focus on the Shewanella population. Results in this study highlighted the important role of Shewanella species in the ecosystem, particularly as the major source of the notorious carbapenemase gene, bla _OXA-48. Control measures should be implemented to prevent further dissemination of such organisms in the hospital setting and the community.

Keywords: OXA-48-like; Shewanella spp.; genomic characterization; progenitor; transmission.

Fig. 1.. Phylogenetic tree of Shewanella spp. A total of 638 non-duplicated genome sequences were retrieved from the NCBI genome database and were used to build the phylogenetic tree. This tree was mid-rooted and visualized using iTOL. The circles from the innermost to outermost indicated the species and the production of OXA-48-like carbapenemase by each strain. The 72 strains that shared <95% identity with the reference genomes were labelled with ‘other’ to indicate that their species were not resolved.

Fig. 2.. Phylogenetic tree of all OXA-48-like carbapenemases. Cladogram of the tree of bla_OXA-48-like genes with clades annotated on the branches. A total of 58 OXA-48-like carbapenemases publicly available as of 1 December 2023 are included. The annotation alongside different variants indicates the species from which the corresponding OXA-48-like carbapenemase was reported and the accession number of the associated nucleotide acid sequence. The variants reported from Shewanella spp. are annotated with blue fonts. The amino acid sequence alignment of the 58 OXA-48-like carbapenemases is shown in Figure S1.

Fig. 3.. Phylogenetic tree of Shewanella spp. in this study. The background colour of the strains indicates the source of the corresponding strains which are from a clinical setting (pink), hospital sewage (green) and river (blue), respectively (strains from the three sources are denoted with IDs beginning with C, F and H, respectively). The innermost to outermost circles in this tree indicate the species, the production of OXA-48-like carbapenemase and the presence of the carbapenemase genes bla_OXA-55-like and bla_NDM-1, respectively.

Fig. 4.. Heatmap of antimicrobial resistance genes carried by the Shewanella spp. in this study. Horizontal axes represent the antimicrobial resistance genes, and vertical axes represent the strain IDs. Red and white boxes represent the presence and absence of the corresponding items among sequenced isolates, respectively. The gradient identity bar indicates the percentage similarity of related genes. The similarity tree was calculated using agglomerative hierarchical clustering, with the degree of similarity between different clusters being calculated by the average linkage method and the degree of similarity of different isolates calculated with Spearman’s rank correlation coefficient.

Fig. 5.. Genetic context of bla_OXA-48-like genes in this study. Cyan, blue and orange arrows indicate the antibiotic resistance gene bla_OXA-48-like, mobile genetic element and other ORFs, respectively. Shading areas indicate the region of genetic elements sharing sequence identities. A number of strains with the corresponding genetic arrangements are given in brackets. Subtypes of the bla_OXA-48-like genes are labelled alongside the corresponding arrows.