The role of the ionophore calcimycin in the fight for iron

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Calcimycin produced by the soil bacterium Streptomyces chartreusis is a carrier ionophore that transports bivalent metal cations. It can only cross membranes as a calcimycin-cation complex, so that overall transport is electroneutral. We could show that in soil-dwelling Bacillus subtilis, calcimycin disturbs the metal homeostasis, causing depletion of cellular iron and manganese while calcium accumulates. Antibacterial activity of the ionophore increases under low-iron and low-manganese conditions. B. subtilis responds to calcimycin by upregulating siderophore synthesis and the oxidative stress response.Since iron is a highly contested micronutrient in soil, we seek a better understanding of the role of calcimycin in the fight for iron. Does calcimycin primarily serve to eliminate competitors? Is calcimycin a sophisticated tool for stealing iron from other soil-dwellers? Does it prompt xenosiderophore production for exploitation of additional iron sources? To address these questions we will investigate the contributions of calcium influx and iron/manganese efflux to the antibacterial effects of calcimycin. We will quantify calcimycin and siderophore levels in mixed cultures of S. chartreusis and B. subtilis and study the iron flux in mixed cultures employing wild-type strains as well as calcimycin-deficient S. chartreusis and siderophore-deficient B. subtilis strains.