Genomic insights into the circulation of pandemic fluoroquinolone-resistant extra-intestinal pathogenic Escherichia coli ST1193 in Vietnam

Abstract

Extra-intestinal pathogenic Escherichia coli (ExPEC) ST1193, a globally emergent fluoroquinolone-resistant clone, has become an important cause of bloodstream infections (BSIs) associated with significant morbidity and mortality. Previous studies have reported the emergence of fluoroquinolone-resistant ExPEC ST1193 in Vietnam; however, limited data exist regarding the genetic structure, antimicrobial resistance (AMR) determinants and transmission dynamics of this pandemic clone. Here, we performed genomic and phylogenetic analyses of 46 ST1193 isolates obtained from BSIs and healthy individuals in Ho Chi Minh City, Vietnam, to investigate the pathogen population structure, molecular mechanisms of AMR and potential transmission patterns. We further examined the phylogenetic structure of ST1193 isolates in a global context. We found that the endemic E. coli ST1193 population was heterogeneous and highly dynamic, largely driven by multiple strain importations. Several well-supported phylogenetic clusters (C1-C6) were identified and associated with distinct bla_CTX-M variants, including bla_CTXM-27 (C1-C3, C5), bla_CTXM-55 (C4) and bla_CTXM-15 (C6). Most ST1193 isolates were multidrug-resistant and carried an extensive array of AMR genes. ST1193 isolates also exhibited the ability to acquire further resistance while circulating in Vietnam. There were phylogenetic links between ST1193 isolates from BSIs and healthy individuals, suggesting these organisms may both establish long-term colonization in the human intestinal tract and induce infections. Our study uncovers factors shaping the population structure and transmission dynamics of multidrug-resistant ST1193 in Vietnam, and highlights the urgent need for local One Health genomic surveillance to capture new emerging ExPEC clones and to better understand the origins and transmission patterns of these pathogens.

Keywords: E. coli; ExPEC; ST1193; bloodstream infections; fluoroquinolone resistance.

Fig. 1.

Phylogenetic structure of E. coli ST1193 isolates from Vietnam. ML phylogeny of E. coli ST1193 in Vietnam. The ML tree was rooted using E. coli strain PAR (ST14cc) as an outgroup. Node colours correspond to different variants of the bla _CTX-M genes. The tip labels highlighted in grey indicate isolates from human carriers. Bar, number of SNPs per site. Black stars indicate bootstrap support values ≥80 % on internal nodes, with larger stars indicating higher bootstrap values. The heat map shows the presence (blue and red colour) or absence (grey colour) of resistance genes and plasmid replicon type/alleles. The multireplicon IncF plasmids are subtyped using FAB (FII:FIA:FIB) formulae by the allele type and number identified for each replicon. Prefixes F- and B- indicate the absence of the FII and FIB replicons, respectively.

Fig. 2.

Phylogeny of Vietnamese E. coli ST1193 isolates in a global context. ML phylogeny reconstructed from a global database of ST1193 E. coli, rooted using E. coli strain PAR (ST14cc) as an outgroup. The tip colours correspond to different variants of the bla _CTX-M gene. The red tip labels indicate isolates within the six clusters C1–C6 identified in this study. Bar, number of SNPs per site. Black stars indicate bootstrap support values ≥80 % on internal nodes, with larger stars showing higher bootstrap values. The outer ring shows the location from which the isolates were reported.

Fig. 3.

blast comparisons of bla _CTX-M-27-carrrying plasmids identified in our ST1193 isolates and previously published ST1193 and ST131 isolates from Vietnam. The central circle indicates the full reference sequence of bla _CTX-M-27-carrying plasmid pMO (IncF1:A2:B20) from an ST131 isolate in Brazil (accession number: MG886288). The two innermost rings show the GC content and GC skew of the reference plasmid. The remaining concentric rings show the nucleotide similarity between the reference plasmid and the bla _CTX-M-27-carrrying plasmids identified in previously published ST131 and ST1193 isolates from Vietnam (isolates: ST131-HN, ST1193-HN; accession numbers: SRR11392822, SRR11392956) and our ST1193 isolates (C1, C2, C3, C5). The outermost ring shows the annotations of the reference plasmid, in which the conjugation module shared between IncF-:A1:B10 (C1) and IncF1:A2:B20 plasmids is highlighted in red.