National reference surveillance in France detected an emergent lineage of Salmonella enterica serovar Typhi, genotype 2.3.1, increasingly associated with travel to West Africa. Isolates of this lineage combined a classical multidrug resistance phenotype with decreased susceptibility and resistance to fluoroquinolones, creating a multidrug-resistant (MDR) and ciprofloxacin-resistant (CIPR) profile of clinical concern.
This lineage represents non–H58 S. Typhi that has undergone local evolutionary events, including plasmid acquisition, chromosomal integration of MDR determinants, and selection of a chromosomal mutation in the DNA gyrase gene associated with quinolone resistance. These genomic changes explain treatment-relevant resistance patterns observed in returned travellers and indicate an expanding public-health threat in the region of probable origin.
Between 2016 and 2025, the National Reference Center for Escherichia coli, Shigella, and Salmonella at the Institut Pasteur received 1,603 nonredundant S. Typhi isolates for expert analysis. Among these, 167 isolates were identified as genotype 2.3.1.
Patient characteristics for the 167 genotype 2.3.1 cases included a median age of 28 years (range 2–85), with 64.7% female and 35.3% male. Travel history was reported for 135 (80.8%) of patients, most indicating travel to African countries, providing a surveillance signal linking these isolates epidemiologically to Africa.
The study combined conventional microbiologic testing and whole-genome sequencing to characterize isolates. Antimicrobial susceptibility testing and genomic analyses identified resistance genes, plasmid markers, and chromosomal mutations. Phylogenetic reconstruction, including a maximum-likelihood tree of genotype 2.3.1 genomes, was used to infer relationships among isolates and to reconstruct evolutionary events. Appendices provided detailed isolate-level data and sequencing results.
A characteristic MDR profile, designated MDRA, comprised the genes blaTEM-1, strA, strB, aadA1, sul1, sul2, dfrA1, and tet(B). Isolates carrying this MDRA profile showed resistance to ampicillin, streptomycin, sulfonamides, trimethoprim, cotrimoxazole, and tetracycline. Separately, the chromosomal mutation gyrA S83F was identified and accounts for nalidixic acid resistance and reduced susceptibility to ciprofloxacin; isolates with this mutation met criteria for ciprofloxacin resistance.
In 2022, investigators obtained 35 MDR–CIPR S. Typhi isolates from persons returning from Senegal; all belonged to genotype 2.3.1, carried the MDRA gene set, and harbored gyrA S83F, with ciprofloxacin MICs in the range reported in the study. Only one similar isolate had been previously recorded in 2021. From 2023 onward, 79 genotype 2.3.1 isolates recovered were CIPR, and 71 displayed the MDRA profile. Additional database genomes included 52 genotype 2.3.1 sequences obtained since 2022; among those, 39 carried the MDRA–CIPR profile and most also had the gyrA S83F mutation.
Phylogenetic analysis of 207 genotype 2.3.1 isolates from the Institut Pasteur collection plus published genomes (208 total with outgroup) placed the emerging MDR–CIPR cluster within genotype 2.3.1. The authors reconstructed an evolutionary history in which this lineage locally acquired two different MDR plasmids over an approximate 25-year interval. One acquisition involved an IncHI1 plasmid, whose MDR region later became integrated into the chromosome, stabilizing multidrug resistance even after plasmid loss.
After stable chromosomal integration of the IncHI1 MDR region, the lineage subsequently acquired a gyrA point mutation (S83F) that confers quinolone resistance, producing the combined MDRA–CIPR phenotype observed in recent isolates. The genomic data therefore indicate stepwise evolution: plasmid acquisition, chromosomal integration of MDR genes, and selection of chromosomal mutations conferring fluoroquinolone resistance.
A substantial portion of recent genotype 2.3.1 isolates were epidemiologically linked to Senegal. The number of genotype 2.3.1 isolates associated with Senegal rose sharply after 2021: the study reported 35 such isolates in 2022, a decrease from 21 in 2023 to 8 in 2024, and then a peak of 50 in 2025. These temporal changes include variations potentially influenced by travel patterns; the unusually low numbers of S. Typhi isolates in 2020–2021 are noted as related to COVID-19 travel restrictions.
Additional genotype 2.3.1 genomes in the database originated from travellers to other West African countries, including Guinea, Guinea-Bissau, Niger, Nigeria, Mauritania, The Gambia, and Benin, supporting a regional distribution of the emerging MDR–CIPR genotype.
The documented local evolution of a non–H58 S. Typhi lineage toward stable chromosomal MDR and fluoroquinolone resistance highlights the need for enhanced genomic surveillance in West Africa. The emergence of a genotype 2.3.1 cluster combining the IncHI1-derived chromosomal MDR region and gyrA S83F-mediated ciprofloxacin resistance could reduce the effectiveness of commonly used oral antimicrobials for typhoid fever in affected areas.
These findings emphasize the value of integrating travel-associated isolate surveillance with genomic analyses to detect and track evolving AMR threats. The study's data support continued monitoring and may inform empirical treatment guidance and public-health responses in regions where this lineage is emerging.
Genomic surveillance at the Institut Pasteur uncovered an emergent genotype 2.3.1 S. Typhi lineage in West Africa that acquired MDR plasmids, integrated the IncHI1 MDR region into the chromosome, and later developed gyrA S83F-associated ciprofloxacin resistance. The lineage's expansion among travellers returning from West Africa between 2021 and 2025 underscores the need for regional genomic AMR surveillance and consideration of changing antimicrobial susceptibilities in clinical management.