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Updated: Jun 24, 2026

Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Resistance to trimethoprim/sulfamethoxazole and Tropheryma whipplei
Florence Fenollar1, Jean-Marc Rolain, Laurent Alric
1Université de la Méditerranée, Unité des Rickettsies, URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France.
Abstract:
Whipple's disease (WD) is a chronic infection caused by Tropheryma whipplei. A 1-year treatment of oral trimethoprim/sulfamethoxazole (SXT) is commonly used. Advances in the culture of T. whipplei have allowed for full genome sequencing and antibiotic susceptibility testing, which has demonstrated resistance of T. whipplei to trimethoprim. Several mutations in the folP gene that encodes dihydropteroate synthase, the target of sulphonamides, has been reported for one patient with clinically acquired resistance to SXT. Here we report three new patients who experienced clinically acquired resistance to SXT during treatment and one patient with biological failure. Sixty-two folP sequences from DNA samples of 59 WD patients were also obtained. Among the detected amino acid changes, two positions (N4S and S234F) significantly predicted secondary sulfamethoxazole failure (four of five). We suggest that these mutations should be detected at the time of WD diagnosis by sequencing folP in order to avoid sulfamethoxazole monotherapy.
Insights
Whipple's disease treatment with trimethoprim/sulfamethoxazole can fail due to Tropheryma whipplei resistance. Sequencing the folP gene can identify mutations predicting treatment failure, guiding better therapeutic choices.
Area of Science:
- Infectious Diseases
- Microbiology
- Genetics
Background:
- Whipple's disease (WD) is a chronic bacterial infection caused by Tropheryma whipplei.
- Standard treatment involves a 1-year course of oral trimethoprim/sulfamethoxazole (SXT).
Observation:
- Tropheryma whipplei exhibits resistance to trimethoprim, a component of SXT.
- Mutations in the folP gene, encoding the target of sulfonamides, are linked to SXT resistance.
- Three new patients developed acquired resistance to SXT during WD treatment, with one experiencing biological failure.
Findings:
- Analysis of 62 folP sequences from 59 WD patients revealed specific amino acid changes.
- Two mutations, N4S and S234F at key positions, significantly predicted secondary sulfamethoxazole failure in four out of five cases.
Implications:
- folP gene sequencing at diagnosis can identify patients at risk of SXT failure.
- Detecting these mutations may help avoid sulfamethoxazole monotherapy and guide alternative treatment strategies.
- This approach can improve treatment outcomes for Whipple's disease by personalizing antibiotic selection.
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