Thymol disrupts the membrane integrity of Salmonella ser. typhimurium in vitro and recovers infected macrophages from oxidative stress in an ex vivo model

Abstract

Salmonella is a common bacterial enteropathogen responsible for many deaths every year. In the present study, we evaluated the mechanism of action of thymol against Salmonella ser. typhimurium, as well as its potential to induce intracellular killing and recovery from oxidative stress in macrophages. The minimum inhibitory concentration (MIC) of thymol against S. typhimurium was found to be 750 mg/l, and the CFU count decreased in a time-dependent manner. Excessive release of cellular materials and potassium ion also occurred in a time-dependent manner. Scanning electron microscopy showed disruption of membrane integrity. Intracellular killing capacity of macrophages was enhanced upon thymol treatment compared to control untreated cells. Thymol significantly reduced production of nitric oxide in a time-dependent manner, as well as the glutathione level. Disruption of membrane integrity was confirmed as the principle mechanism of action of thymol against S. typhimurium. Further, its potent role in inducing intracellular killing of S. typhimurium and recovery from oxidative stress in macrophages suggests that thymol can be applied as a naturally occurring drug against S. typhimurium in place of synthetic drugs.