The role of the ionophore calcimycin in the fight for iron

由土壤细菌Streptomyces chartreusis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。它只能以钙霉素-阳离子络合物的形式跨膜，因此整个转运是电子中和的。我们可以证明，在土壤栖息的枯草芽孢杆菌中，钙霉素扰乱了金属的动态平衡，导致细胞内铁和锰的消耗，而钙的积累。在低铁、低锰条件下，离子载体的抗菌活性增强。枯草杆菌对钙霉素的反应是通过上调铁载体的合成和氧化应激反应来实现的。由于铁是土壤中一种极具争议性的微量营养素，我们试图更好地了解钙霉素在争夺铁的过程中所起的作用。钙霉素主要用于消除竞争对手吗？钙霉素是一种从其他土壤居民那里窃取铁的复杂工具吗？它是否促进了外星人铁载体的生产，以开发更多的铁源？为了解决这些问题，我们将研究钙内流和铁/锰外流在钙霉素抗菌作用中的作用。我们将量化沙门氏菌和枯草芽孢杆菌混合培养物中钙霉素和铁载体的水平，并研究使用野生型菌株以及缺乏钙霉素的沙门氏菌和铁载体缺陷的枯草杆菌混合培养物中的铁通量。

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.