Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509. (September 2022) - Che, Yanlin
Highlights: A complete genome sequence was carried out on multidrug-resistant Nocardia farcinica . The transposon-mediated sul1 gene is found to contribute to sulfamethoxazole resistance. The transposon of this gene possibly acts as a vehicle for the dissemination of resistance. ABSTRACT: Objectives: The objective of this study is to explore the molecular basis of trimethoprim-sulfamethoxazole (SXT) resistance in Nocardia, an SXT-resistant N. farcinica strain, named SZ 1509, by whole-genome sequencing. Methods: Antimicrobial susceptibility testing of SZ 1509 was performed by broth microdilution, Etest, and disk diffusion arrays. Genome sequencing and analysis were performed to discover the SXT resistance determinant and its genetic context. Inverse PCR was conducted to confirm the circular form of the composite transposon. PCR for the sul1 gene was performed among SXT-susceptible isolates. Results: SZ 1509 is resistant to many drugs, especially SXT, with a minimum inhibitory concentration (MIC) of up to 32/608 µg/mL (ratio of 1:19 for trimethoprim: sulfamethoxazole). Its assembled genome consists of one chromosome and four plasmids with a total size of 6 613 629 bp and 71.1% of GC content. The plasmid 2 was found to carry one IS 6 -composite transposon containing IS 6100 carrying the sul1 gene, one tellurite resistance gene TerC, and several transcriptional regulators. Inverse PCR analyses showed its circular form. All 10 SXT-susceptible isolates do not contain sul1 . In addition, mutations with strong associations to SXT resistance were not conclusive. Conclusion: This is the first study to elucidate the transposon-mediated sulfamethoxazole resistance in N. farcinica . Our results provide insights on acquired drug resistance of N. farcinica and further suggest that the prevalence and correlation of this resistance's determinants in clinical isolates should be continuously monitored to provide effective clinical management of its resultant diseases.