Sessions

Antimicrobial resistance, one of the major challenges of our time, represents a global threat to both public and animal health. Bacterial infections that were previously susceptible and responded well to antimicrobial treatment can, in many cases, no longer be effectively treated with the agents that were formerly considered first-line therapies. The use of antibiotics for the prevention of respiratory and gastrointestinal diseases and for growth promotion, together with their excessive and inappropriate use, has contributed to the emergence of resistant bacteria. Numerous studies have demonstrated a direct link between bacterial adaptability, the development of resistance mechanisms, oxidative stress, and cellular stress responses. These findings have opened up new opportunities for the development of therapeutic strategies, in which antioxidant compounds administered at appropriate concentrations may play a role.

In our study, we investigated naturally derived antioxidants, namely curcumin, luteolin, and grape seed proanthocyanidins, with the aim of determining whether these compounds can reduce the development of enrofloxacin resistance in E. coli. Under in vitro conditions, the minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of the antioxidants against poultry-derived E. coli were determined. In addition, the interactions between the antioxidants and enrofloxacin were characterized by calculating the fractional inhibitory concentration (FIC) index. The dynamics of resistance development were investigated over ten consecutive serial passages in groups treated with enrofloxacin alone and in groups treated with combinations of enrofloxacin and antioxidants. Subsequently, whole-genome sequencing and mutation analysis were performed to identify the genetic alterations that had emerged during the experiment.

The results of the synergy assays showed that curcumin and luteolin could be safely applied in combination with enrofloxacin over a broad concentration range without affecting its antibacterial activity, whereas the effect of proanthocyanidins was concentration dependent. The addition of antioxidants resulted in changes in the gene repertoire of the passaged bacterial populations compared with the parental strain. We also identified point mutations resulting in amino acid substitutions that may be associated with a reduction in resistance.

Our findings indicate that antioxidants may represent promising agents for use as adjuncts to enrofloxacin therapy in poultry health management, while their potential application as feed additives may contribute to efforts to combat antimicrobial resistance.