Commensal Escherichia coli are a reservoir for the transfer of XDR plasmids into epidemic fluoroquinolone-resistant Shigella sonnei

Abstract

Data Availability All raw genomic data that support the findings of this study have been deposited in the European Nucleotide Archive (project: PRJEB30967) and can be accessed via this link (https://www.ebi.ac.uk/ena/data/search?query=PRJEB30967). Details about accession numbers of S. sonnei isolates can be found in Supplementary Table 1. The S. sonnei reference genome Ss046 chromosome (accession number: NC_007382), virulence plasmid pSs046 (accession number: NC_007385.1) and three small plasmids commonly found in global lineage III S. sonnei: spA (accession number: NC_009345.1), spB (accession number: NC_009346.1), and spC (accession number: NC_009347.1) were downloaded from GenBank. Raw MinION reads for plasmid p01_0123 are deposited in ENA (accession number: ERS3050922). Source data for main figures [Figs. 2a, 3a, 4] and Extended Data [ED Figs. 1, 2] are provided with the paper. Additional data that support the findings of this study are available from the corresponding author upon request. Author contributions PTD, MAR, and SB designed the study. PTD performed data analysis and interpreted the results under the scientific guidance of MAR and SB. PTD drafted the paper, with MAR and SB revising and structuring the paper. PTD and HNDT performed whole genome sequencing. PTD and TNTN performed plasmid isolation, digestion and sequencing. PTD, FA, and TNTN performed the plasmid conjugation experiments. HTT performed basic microbiology work. HCT and CB assisted in the design of laboratory experiments. DVT recruited patients and performed the clinical work required for the study. HCT, CB, and GET contributed to the editing of the paper. All authors read and approved the final draft.

The Gut Microbiome of Healthy Vietnamese Adults and Children Is a Major Reservoir for Resistance Genes Against Critical Antimicrobials

“…One of the best examples has been the sequential emergence of resistance to fluoroquinolones and third-generation cephalosporins in Shigella sonnei [ 11 ]. This trend has been facilitated by self-transmissible plasmids carrying genes encoding extended-spectrum β-lactamases (ESBLs), which can then acquire additional genes encoding resistance to macrolides and aminoglycosides, leading to the emergence of extensively drug-resistant (XDR) Shigella sonnei [ 12 ].…”

The evolutionary history of Shigella flexneri serotype 6 in Asia

“…In order to investigate the AMR profiles of Sf6, we used a genotyping approach, supported by the consistency between AMR genotyping and phenotyping results in Shigella as reported previously [49]. The resistome of Sf6 revealed a similar trend as observed in other Shigella species, in which resistance to first-generation antimicrobials for shigellosis treatment is commonplace [12, 47, 48, 50, 51]. In particular, genetic elements conferring resistance to sulphonamide ( sul1 or sul2 , n =89/96), trimethoprim ( dfrA variants, n =89/96), and tetracycline ( tetA or tetB , n =92/96) were prevalent across the phylogeny ().…”

“…Likewise, resistances to third-generation cephalosporins and quinolone were both more prevalent in S. sonnei , with higher occurrence of bla CTX-M variants and gyrA / parC mutations [13, 44, 51].…”

Accessory Genome Dynamics and Structural Variation of Shigella from Persistent Infections

“…Here, we observed the acquisition of two different beta-lactamase genes (one extended spectrum) in two carriage-associated pairs, one S. flexneri 2a and one S. sonnei . Since we were unable to fully reconstruct the genetic context for these genes, we could not identify their potential origin, although a contig carrying the bla TEM-1 gene in S. sonnei shared a high level of similarity with an E. coli plasmid, and HGT of AMR plasmids between Shigella and E. coli in the gut has been previously suggested ( 34 – 36 ). Thus, the acquisition of this resistance gene could have been facilitated by HGT from E. coli or other bacterial species in the gut.…”