Abstract
Antibiotic resistance is a growing problem due to the rise in diseases associated with resistant pathogens. The bacterial SOS response is a genetic stress-response pathway whose primary role is DNA repair. It can be activated by DNA damage induced by antibiotics and contribute indirectly to the emergence of resistance through mutagenic DNA polymerases, horizontal gene transfer, and the promotion of bacterial persistence and tolerance to antibiotics. Inhibiting this pathway represents a promising strategy to reduce the appearance of resistant variants. Here, we aimed to evaluate the antibacterial, antibiotic-modulating, and SOS-inhibitory capacities of Lippia origanoides extract (LOE) and pinocembrin, using the Escherichia coli PQ37 strain and the SOS Chromotest assay. Ciprofloxacin was used as the test antibiotic and proved to be a potent inducer of the SOS response in E. coli. In co-treatments with this antibiotic, pinocembrin (0.097 mM) exhibited a synergistic effect on the antibiotic's activity, reducing its minimum inhibitory concentration by approximately fourfold. Furthermore, pinocembrin inhibited the ciprofloxacin-induced SOS response in a concentration-dependent manner, with significant inhibition starting at 0.031 mM (r = -0.87, p < 0.05). These results indicate that pinocembrin can be an adjuvant in combination antibiotic therapy, as it potentiates antibiotic activity while simultaneously suppressing the bacterial SOS response, a mechanism that could minimize the risk of antibiotic resistance development.
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