Genomic Signature of Multi-Drug Resistant Salmonella Typhi related to a Massive Outbreak in Zambia during 2010 - 2012.

Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the MLST, haplotype, plasmid replicon, antimicrobial resistance genes, and the genetic relatedness by Single Nucleotide Polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients with a fatality rate of 0.5%. Most isolates (83.0%) were multi-drug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype; H58B. Most isolates contained a chromosomally translocate region containing seven antimicrobial resistance genes; catA1, blaTEM-1, drfA7, sul1/2, and strA/B, fragments of incQ1plasmid replicon, IP type 2 integron, and the mer operon. The isolates were clonal diversified containing 35 deletions, 415 SNPs and 21 bifurcation points in the phylogenetic tree with relation to strains from India and Central Africa. The phylogenetic analysis and deletion content clearly indicated that the isolates involved in the outbreak were only distantly related suggesting that multiple clones and lineages were responsible for the outbreak. In contradiction to the common view that the emerging global S. Typhi haplotype; H58B, contains the MDR incHI1 plasmid is responsible for the majority of typhoid infections; we found that a new variant of the haplotype harbouring a chromosomally translocated region containing the MDR islands of incHI1 plasmid emerged in Zambia. This will chance the perception of the term “classical MDR” currently being associated with the incHi1 plasmid.