Preliminary Study of Resistance Mechanism of to SYAUP-CN-26.

SYAUP-CN-26 (1, 2-((3-bromophenethyl)amino)--(4-chloro-2-trifluoromethylphenyl) cyclohexane-1-sulfonamide) is a novel sulfonamide compound with excellent activity against . The present study sought to explore the mutant of resistant to SYAUP-CN-26 using SYAUP-CN-26 plates. Moreover, the cell membrane functions of , histidine kinase activity, relative conductivity, triglyceride, and cell membrane structure were determined, and the target gene histidine kinase Bos1 (AF396827.2) of procymidone was amplified and sequenced. The results showed that compared to the sensitive strain, the cell membrane permeability, triglyceride, and histidine kinase activity of the resistant strain showed significant changes. The relative conductivity of the sensitive strain increased by 6.95% and 9.61%, while the relative conductivity of the resistant strain increased by 0.23% and 1.76% with 26.785 µg/mL (EC) and 79.754 µg/mL (MIC) of SYAUP-CN-26 treatment. The triglyceride inhibition rate of the resistant strain was 23.49% and 37.80%, which was 0.23% and 1.76% higher than the sensitive strain. Compared to the sensitive strain, the histidine kinase activity of the resistant strain was increased by 23.07% and 35.61%, respectively. SYAUP-CN-26 significantly damaged the cell membrane structure of the sensitive strain. The sequencing of the Bos1 gene of the sensitive and resistant strains indicated that SYAUP-CN-26 resistance was associated with a single point mutation (P348L) in the Bos1 gene. Therefore, it was inferred that the mutant of resistant to SYAUP-CN-26 might be regulated by the Bos1 gene. This study will provide a theoretical basis for further research and development of sulfonamide compounds for and new agents for the prevention and control of resistant .