A novel mathematical model for studying antimicrobial interactions against viable but non-culturable Campylobacter...

Campylobacter jejuni is a major pathogen associated with gastrointestinal illness and is frequently detected in poultry products. Its ability to enter the viable but non-culturable (VBNC) state is an adaptive survival strategy triggered by adverse conditions. Consequently, the processing conditions involved in poultry production can potentially induce C. jejuni into the VBNC state, posing risks to food safety and public health. This study aimed to evaluate the antimicrobial effectiveness of carvacrol, diallyl sulfide, and Al₂O₃ nanoparticles (NPs) and investigate their synergistic interactions against VBNC C. jejuni under simulated poultry processing conditions. The time-kill assay demonstrated that Al₂O₃ NPs achieved >1 log CFU/mL reductions at 0.3 mg/mL, while carvacrol and diallyl sulfide required higher concentrations (0.8 mg/mL and 1.6 mg/mL, respectively) to achieve comparable reductions. While additive effects were observed for all combinations, the interactions were further examined using the combination index. The mathematical model effectively simulated the antimicrobial effects and interactions across varying levels of inhibition, confirming the potent antimicrobial activity of Al₂O₃ NPs. While carvacrol and diallyl sulfide exhibited additive effects in combination, synergistic interactions (combination index <1) were identified for binary and ternary combinations with Al₂O₃ NPs, including carvacrol/Al₂O₃ NPs, diallyl sulfide/Al₂O₃ NPs, and carvacrol/diallyl sulfide/Al₂O₃ NPs. These findings underscore the potential of Al₂O₃ NPs, individually or in combination with plant-based antimicrobials, to mitigate VBNC C. jejuni and improve food safety. The mathematical model presents an alternative approach to developing novel antimicrobial strategies.