Alkaline stress inhibits the growth of Staphylococcus epidermidis by inducing TCA cycle-triggered ROS production.

Many species of bacteria interact on the human skin to form a certain microbiome. Delftia acidovorans, a bacterium detected from human skin, inhibits the growth of S. epidermidis, a dominant bacterium of the human skin microbiota. Here, we show that ammonia secreted by D. acidovorans inhibits the growth of S. epidermidis by increasing the pH value of the medium. The pH value of D. acidovorans culture supernatant (CS) was higher than that of the medium without culture. The inhibitory activity of the D. acidovorans CS against the growth of S. epidermidis was decreased by neutralization with hydrochloric acid. Genes encoding enzymes related to ammonia production were found in the D. acidovorans genome. Moreover, the D. acidovorans CS contained a high concentration of ammonia. The addition of ammonia to S. epidermidis culture led to an increase in the reactive oxygen species (ROS) production and inhibited S. epidermidis growth. The addition of sodium hydroxide also led to an increase in the ROS production and inhibited S. epidermidis growth. The inhibitory activity of ammonia and sodium hydroxide against S. epidermidis growth was suppressed by malonic acid, an inhibitor of succinate dehydrogenase in the tricarboxylic acid (TCA) cycle, and N-acetyl-l-cysteine, a free radical scavenger. These findings suggest that D. acidovorans secretes ammonia and alkaline stress inhibits the growth of S. epidermidis by inducing TCA cycle-triggered ROS production.