A genomic snapshot of Salmonella enterica serovar Typhi in Colombia

Abstract

Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S. Typhi, in 2006. Here, we characterized 77 representative Colombian S. Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S. Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S. Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S. Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S. Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S. Typhi clones and mapping transmission. The genetic diversity of pathogens such as S. Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS.

Fig 1. Colombian Salmonella Typhi isolates selected for whole genome sequencing.

PFGE-XbaI dendrogram generated with Dice coefficient and UPGMA clustering method (tolerance and optimization 1.5%) of the 77 selected S. Typhi isolates with isolate identification and PFGE pattern code. The red boxes indicate isolates from epidemiological confirmed outbreaks (A-H).

Fig 2. The phylogenetic structure of Salmonella Typhi in Colombia.

SNP based RAxML generated Maximum Likelihood phylogenetic tree of 77 selected Salmonella Typhi isolates. Branches are coloured by genotype (numbers shown). Column 1 indicates year of isolation, column 2 indicates department (state) of isolation, column 3 indicates the presence (brown) of SNPs in the QNDR and column D indicates acquired AMR genes (see legend). The map was drawn by inkscape v1.0.1 an Open Source Scalable Vector Graphics Editor.

Fig 3. WGS and PFGE exhibit a limited correlation for Salmonella Typhi genotyping.

The branches of the SNP based RAxML phylogenetic tree and the first column are coloured by genotype. The sequential columns highlight the PFGE patterns that were present more than one occasion. i.e., the bottom two isolates of clade 2.5 with PFGE code COINXX.JPPX01.0004 and the top two isolates of clade 3.5 with PFGE code COINXX.JPPX01.0249. All PFGE patterns are additionally listed under PFGE code (the PFGE pattern correspond to the last 4 digits of the PFGE code) for enhanced visibility only unique PFGE are listed by code and not highlighted. The year of isolation and department are coloured as in Fig 2. Letter D and G indicate the two outbreaks from which we sequenced more than one isolate, these correspond with outbreak strains D and G in Fig 1.

Fig 4. The phylogenetic location of Colombian Salmonella Typhi in a global context.

SNP based RAxML based phylogenetic tree of the 77 Colombian isolates among 3,382 publicly available non-H58 S. Typhi genome sequences. Branches are coloured by genotype, inner ring depicts country of isolation, Asia in red shades, South East Asia in blue shades, Africa in green shades, Colombia in bright red and other Latin American countries in grey. The middle ring indicates AMR profile, any AMR is shown in light brown and MDR isolates are shown in dark brown. Finally, the outer ring shows number of QRDR SNPs with the colour intensity increases with increasing number of SNPs.