The role of the ionophore calcimycin in the fight for iron

土壤细菌黄绿色链霉菌产生的钙霉素是一种运输二价金属阳离子的载体离子载体。它只能作为钙化霉素-阳离子络合物穿过膜，因此整体运输是电中性的。我们可以证明，在土壤中的枯草芽孢杆菌中，钙霉素扰乱了金属稳态，导致细胞铁和锰的消耗，而钙的积累。在低铁和低锰条件下，离子载体的抑菌活性增强。枯草芽孢杆菌通过上调铁蛋白合成和氧化应激反应来响应钙霉素。由于铁在土壤中是一种高度竞争的微量营养素，我们寻求更好地理解钙霉素在铁的争夺中的作用。钙霉素的主要作用是消灭竞争者吗？钙霉素是一种从其他土壤居民那里窃取铁的复杂工具吗？它是否会促进异种铁元素的生产以开采更多的铁资源？为了解决这些问题，我们将研究钙内流和铁/锰外排对钙霉素抗菌作用的贡献。我们将量化黄曲霉和枯草芽孢杆菌混合培养中钙霉素和铁载体的水平，并研究野生型菌株以及缺乏钙霉素的黄曲霉和缺乏铁载体的枯草芽孢杆菌混合培养中的铁通量。

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.