ena-STUDY-Fondation Merieux-21-06-2018-08:31:49:429-6203
Salmonella Typhi in Bangladesh: exploration of genomic diversity and antimicrobial resistance
Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a global public health concern due to increasing antimicrobial resistance (AMR). Detailed genetic characterization of AMR in countries where S. Typhi is endemic is necessary to prevent further spread of AMR and fight drug-resistant clones. We studied whole genome sequences (WGS) of 536 S. Typhi isolates collected in Bangladesh between 1999 and 2013, and compared these with data from a recent outbreak in Pakistan, reported by Klemm et al. [mBio 9:e00105-18, doi: 10.1128/mBio.00105-18] and a laboratory surveillance in Nepal, by Britto et al. [pntd 12(4):e0006408, doi: 10.1371/journal.pntd.0006408]. WGS had a high sensitivity and specificity for prediction of ampicillin, chloramphenicol, cotrimoxazole and ceftriaxone AMR phenotypes, but needs further improvement for ciprofloxacin resistance. We detected a new local lineage of genotype 4.3.1 named lineage Bd, which recently diverged into a sublineage (named Bdq) containing qnr genes and gyrA mutations with median ciprofloxacin MIC of 4.0 µg/mL. Our ceftriaxone-resistant isolate was characterized by the blaCTX-M-15 gene and had a distinct genotype compared to extensively drug resistant (XDR) isolates from Pakistan, indicate different point of origin for AMR in different countries. Genotype 4.3.1 was dominant in all three countries, but formed country- and lineage-specific clusters in the maximum-likelihood phylogenetic tree. Thus, multiple independent genetic events leading to ciprofloxacin and ceftriaxone resistance may have occurred in Bangladesh, Pakistan and Nepal; such mutational events may enhance the risk of global spread of these highly resistant clones.
Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a global public health concern due to increasing antimicrobial resistance (AMR). Detailed genetic characterization of AMR in countries where S. Typhi is endemic is necessary to prevent further spread of AMR and fight drug-resistant clones. We studied whole genome sequences (WGS) of 536 S. Typhi isolates collected in Bangladesh between 1999 and 2013, and compared these with data from a recent outbreak in Pakistan, reported by Klemm et al. [mBio 9:e00105-18, doi: 10.1128/mBio.00105-18] and a laboratory surveillance in Nepal, by Britto et al. [pntd 12(4):e0006408, doi: 10.1371/journal.pntd.0006408]. WGS had a high sensitivity and specificity for prediction of ampicillin, chloramphenicol, cotrimoxazole and ceftriaxone AMR phenotypes, but needs further improvement for ciprofloxacin resistance. We detected a new local lineage of genotype 4.3.1 named lineage Bd, which recently diverged into a sublineage (named Bdq) containing qnr genes and gyrA mutations with median ciprofloxacin MIC of 4.0 µg/mL. Our ceftriaxone-resistant isolate was characterized by the blaCTX-M-15 gene and had a distinct genotype compared to extensively drug resistant (XDR) isolates from Pakistan, indicate different point of origin for AMR in different countries. Genotype 4.3.1 was dominant in all three countries, but formed country- and lineage-specific clusters in the maximum-likelihood phylogenetic tree. Thus, multiple independent genetic events leading to ciprofloxacin and ceftriaxone resistance may have occurred in Bangladesh, Pakistan and Nepal; such mutational events may enhance the risk of global spread of these highly resistant clones.