Chelerythrine-Mediated Growth Inhibition and Resistance Mechanism in Bacillus tropicus

Area of Science:

• Natural Products Chemistry
• Microbiology
• Plant Pathology

Background:

• Chelerythrine (CHE), a benzophenanthridine alkaloid from *Chelidonium majus* L., exhibits broad-spectrum antimicrobial, anti-inflammatory, and apoptosis-inducing properties.
• Bacillus tropicus is a soil bacterium relevant for biological control in agriculture.
• Understanding CHE's interaction with bacteria is crucial for optimizing its use in microbial control.

Purpose of the Study:

• To investigate the dose-dependent inhibitory effects of CHE on *Bacillus tropicus* growth, biofilm formation, and survival.
• To acclimate a *B. tropicus* strain to high concentrations of CHE and develop a drug-resistant variant.
• To identify the genetic mechanisms underlying CHE resistance in *B. tropicus* using transcriptomics.

Main Methods:

• Systematic examination of CHE's dose-dependent effects on *B. tropicus* growth curves, biofilm development, and survival rates.
• In vitro acclimation of *B. tropicus* through 30 generations of continuous subculturing under increasing CHE concentrations.
• Transcriptomics analysis to compare gene expression profiles between wild-type and CHE-resistant *B. tropicus* strains.

Main Results:

• CHE demonstrated dose-dependent inhibition of *B. tropicus* growth, biofilm formation, and survival.
• A highly CHE-resistant *B. tropicus* strain was successfully acclimated, tolerating up to 300 mg/L CHE.
• Transcriptomics revealed significant alterations in gene activity, with 868 genes upregulated and 539 downregulated in the resistant strain, particularly in sugar metabolism and biofilm pathways.

Conclusions:

• *Bacillus tropicus* exhibits CHE resistance primarily through adjustments in sugar metabolism and biofilm formation pathways.
• The development of CHE-resistant *B. tropicus* opens possibilities for combined formulations for plant disease management.
• This study provides insights into bacterial adaptation mechanisms to natural product-based antimicrobial agents.