West African Typhoid Lineage Accumulates Resistance in Stepwise Genetic Bursts
A genotype 2.3.1 Salmonella enterica serovar Typhi lineage emerging in West Africa has acquired the genetic machinery for multidrug resistance and ciprofloxacin resistance through a series of distinct evolutionary steps. The strain was increasingly detected in travelers returning to France from West Africa, especially Senegal, and its rise now places a historically important enteric fever pathogen on a familiar trajectory toward harder-to-treat disease.
The sequence of events is strikingly ordered. Over roughly 25 years, the lineage locally acquired two different multidrug-resistance plasmids, then lost the IncHI1 plasmid after the resistance region became stably embedded in the chromosome, and finally picked up a gyrA S83F mutation that conferred ciprofloxacin resistance. In practical terms, the bacterium did not merely become resistant once; it assembled resistance in layers, preserving what helped survival while shedding what was no longer necessary.
Travelers Returning From Senegal Carried the New Phenotype
French reference surveillance captured the shift early because enteric fever is notifiable and isolates are routinely forwarded for expert analysis. Between 2016 and 2025, the national reference center received 1,603 Typhi isolates, including 167 of genotype 2.3.1. Most of those patients had travel exposure in Africa, and among the genotype 2.3.1 isolates linked to West Africa, Senegal stood out as the key geographic source in this report.
The first notable cluster appeared in 2022, when 35 MDR-CIPR isolates from travelers returning from Senegal were all genotype 2.3.1. Every isolate carried the same resistance gene set: bla TEM-1, strA, strB, aadA1, sul1, sul2, dfrA1, and tet(B), along with the gyrA S83F mutation. The phenotype followed directly from the genotype, with resistance to ampicillin, streptomycin, sulfonamides, trimethoprim, cotrimoxazole, tetracycline, nalidixic acid, and ciprofloxacin.
Resistance did not stay static. The number of genotype 2.3.1 isolates linked to Senegal fell from 21 in 2023 to 8 in 2024, then surged to 50 in 2025. Since 2023, all 79 isolates recovered have been ciprofloxacin resistant, and 71 also carried the multidrug-resistance profile. In a clinical setting where empiric therapy for typhoid often depends on local resistance patterns, this kind of jump narrows antibiotic options quickly.
The Chromosome Now Carries What Used to Live on a Plasmid
One of the most consequential findings was the absence of a plasmid in the emerging resistant lineage. Long-read sequencing of two isolates confirmed why: the multidrug-resistance region had integrated into the chromosome near STY2890 and STY2889. The inserted segment measured 34,664 bp and was flanked by IS26 elements, a genetic architecture that favors mobility, rearrangement, and persistence.
This chromosomal integration matters because plasmids can be lost when selective pressure changes, but a chromosomally embedded resistance cassette is far more stable. The integrated region contained the full set of eight resistance genes seen in the multidrug-resistant isolates, preserving the phenotype even after the plasmid itself disappeared. A second chromosomal rearrangement also appears to have occurred around bla TEM-1, suggesting IS26-mediated restructuring after the original plasmid-derived segment was inserted.
A short molecular detour can have long bedside consequences.
Phylogeny Places the New Strain Near Older West African Relatives
The evolutionary tree reconstructed from 207 genotype 2.3.1 genomes, plus one older Cameroon isolate from 1958, revealed two main multidrug-resistant branches. The larger branch, MDRA, carried the gene combination seen in the Senegal-associated cluster and included 161 genomes. A smaller branch, MDRB, held 11 genomes with a different resistance gene set and a pST3 IncN plasmid.
The emerging ciprofloxacin-resistant lineage clustered tightly together at the base of the tree. All 154 ciprofloxacin-resistant isolates with the gyrA S83F mutation grouped in a compact cluster, and most also carried the MDRA profile. A previously published MDRA-CIPR genome from Nigeria in 2019 sat closest to this group and likely represents the nearest ancestor identified so far. The pattern suggests a stepwise expansion from a West African reservoir rather than a sudden, isolated acquisition in a single patient.
The broader historical context is familiar to anyone following typhoid genomics. The globally distributed H58 lineage, which emerged in South Asia, also accumulated resistance in stages: first an IncHI1 MDR plasmid, then chromosomal integration of the resistance region, then ciprofloxacin resistance via gyrA mutation. The West African 2.3.1 lineage now resembles that trajectory, though it arose independently and belongs to a different genomic background.
Why the Resistance Pathway Changes Treatment Risk
Typhoid fever remains a human-restricted infection spread through fecally contaminated food or water, so resistant lineages track directly with sanitation gaps and travel-associated exposure. A strain that is resistant to the older oral agents and also less reliably treatable with fluoroquinolones leaves clinicians with fewer empiric options, particularly in settings where blood culture and susceptibility testing are not rapidly available.
The resistance profile described here is not limited to a single mutation or a single drug class. It combines aminoglycoside, sulfonamide, trimethoprim, tetracycline, and beta-lactam resistance with quinolone resistance, and the chromosomal integration of the MDR region suggests the phenotype may persist even without ongoing plasmid selection. In effect, the lineage has crossed from transient acquisition to durable inheritance.
Surveillance Must Track Spread Before the Cluster Widens
French surveillance provided a clear window into the emergence of this strain because isolates from returning travelers were systematically characterized by conventional microbiology and whole-genome sequencing. Without that genomic layering, the evolutionary pathway would have remained much harder to reconstruct. The work also shows how travel medicine can function as an early warning system for resistance emerging in regions where routine genomic surveillance is limited.
The clinical and public health concern is not confined to France. A lineage that is already established in West Africa, has accumulated multiple resistance determinants, and now carries stable chromosomal MDR is positioned for further spread if transmission continues unchecked. Continued genomic surveillance will be essential to follow its geographic expansion, detect additional resistance changes, and inform control measures before treatment failure becomes more common in routine care.