Emergence of Novel Mutations in Extensively Drug-Resistant Salmonella enterica Serovar Typhi from Pakistan

LETTER

In response to the recent discussion on extensively drug-resistant (XDR) typhoid in Pakistan (1), we would like to draw attention to the critical genotypic evolution in Salmonella enterica serovar Typhi strains from Pakistan that would be of interest to the health care community. In 2016, a large outbreak of XDR S. Typhi emerged in Pakistan in the Sindh province (2). From November 2016 until now, >21,000 cases of typhoid were reported from Sindh, among which 70.8% were XDR typhoid. A study in 2017 genetically characterized the linkage of emerged XDR strains with the H58 haplotype and suggested that strains acquired an extended-spectrum β-lactamase-encoding antibiotic-resistant plasmid from Escherichia coli (3). Since then, quite a few cases have been reported from other parts of the country. We characterized S. Typhi strains isolated from Punjab province in 2018 through whole-genome sequencing in collaboration with the CDC and noted certain mutations (3). The sequence of one of the strains (GenBank accession no. CP044007 [chromosome] and CP044008 [plasmid]) carries catA1, dfrA7, and sul1 in a chromosomally integrated IS1-mediated composite transposon at the same location as in Pak60006_2016 (4) but lacks a 7,857-bp internal region containing the partial IncQ1 replicon, aph(3″)-Ib, aph(6)-Id, bla_TEM-1B, and sul2. It may be a single nucleotide polymorphism event mediated by a promiscuous insertion sequence. The partial copy of the IncQ plasmid is embedded in the chromosome. The finding suggests that more stable inheritance for antibiotic resistance genes can be expected from S. Typhi strains over time. There is a dire need to keep track of ongoing deletion events in XDR S. Typhi strains. Routine surveillance of S. Typhi infection is recommended in areas of endemicity to ensure its detection before it is widely spread (5). The rapidly emerging patterns in XDR S. Typhi strains have led to a challenging situation in the region (6). The current ongoing epidemic has led to development of a nationwide action plan developed through national (NIH Pakistan) and international (WHO and CDC) collaboration. The plan is in effect across the country and includes surveillance at the genomic level; selected sites have been sharing the XDR strains with a national reference laboratory for sequence analysis. The joint efforts by different stakeholders are imperative contain the rapidly increasing and evolving S. Typhi strains in Pakistan.