Ampicillin activates Mpk1 phosphorylation in Saccharomyces cerevisiae and ERK1/2 phosphorylation in HepG2 cells

Ampicillin has been widely used to treat bacterial infections. When we used ampicillin to eliminate bacterial contamination in yeast cultures, we observed induction of phosphorylation of MAP kinase 1 (Mpk1), a previously unknown function of ampicillin. We therefore investigated whether ampicillin activates the signal transduction pathway. Phosphorylation of Saccharomyces cerevisiae Mpk1 was induced by ampicillin in a dose- and time-dependent manner through the PKC1-CWI pathway. Mpk1 phosphorylation was maximal after treatment with 3 mM ampicillin for 90 min. Despite activation of Mpk1 phosphorylation, ampicillin did not influence yeast cell growth. Ampicillin reduced miconazole antifungal activity; miconazole had a minimum inhibitory concentration of 3.125 µg/ mL against Candida albicans, which increased to 25 µg/mL after 48 h of treatment with 3 mM ampicillin. Finally, ampicillin activated phosphorylation of ERK1/2 (a mammalian homolog of Mpk1), with maximum effect at 3 mM ampicillin, in human HepG2 cells, but did not influence cell viability. The results of this study clearly indicate that ampicillin activated Mpk1 phosphorylation in yeast and ERK1/2 phosphorylation in HepG2 cells. In addition to its clinical application to eliminate bacteria, ampicillin could also be used to activate Mpk1 or ERK1/2 in the laboratory.

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