A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia

Abstract

Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

Fig. 1. Three polyphyletic super-lineages of S. Concord.

A Neighbour-joining cgMLST tree constructed using EnteroBase showing three different super-lineages in the S. Concord collection. Dots are coloured according to the super-lineage. B Overview of all Salmonella isolates present in EnteroBase on 21/07/2022 that cluster together with S. Concord in the super-lineages HC2000_750, HC2000_141 and HC2000_177997. Dots in the tree are coloured according to the serovar determined by SeqSero2. The data required to reproduce these figures is available via EnteroBase. Scale bars represent the number of cgMLST allele differences.

Fig. 2. Overview of the population structure, metadata, antimicrobial resistance genes and plasmid replicon types of S. Concord super-lineage A.

Maximum likelihood phylogeny for 245 S. Concord isolates belonging to super-lineage A and based on 7148 non-recombinant core SNPs. The tree was rooted on a closely related S. enterica serovar Potsdam isolate that was also part of super-lineage A. Lineage names are indicated in each coloured square (e.g. Lineage 1 = L1). Tips highlighted with a coloured dot were selected for long-read sequencing. Ggtree v2.2.4 was used to plot the tree. Metadata is shown at the right side of the tree together with a summary of commonly occurring AMR genotypes and the presence- (blue cells) or absence (white cells) of common AMR genes and replicon types. The scale bar indicates the number of substitutions per site. ComplexHeatmap v2.8.0 was used to for plotting. Abbreviations: AMR = antimicrobial resistance, MDR = multidrug resistance, ESBL = extended-spectrum beta-lactamase, XDR = extensive drug resistance, PDR = pandrug resistance, sus = susceptible, 3GC = third-generation cephalosporin, AZ = azithromycin.