National Institute for Medical Research, Mill Hill, London, NW7 1AA, England.
Infect Immun. 1973 Mar;7(3):445-56. doi: 10.1128/iai.7.3.445-456.1973.
Previous work suggested that virulent bacteria, which can grow rapidly in serum, must possess a specific mechanism for removing iron from its transferrin complex. Two strains of Escherichia coli were examined with this in mind. Strain O141, which showed inoculum-dependent growth in serum and multiplied in the mouse peritoneum, secreted iron-binding catechols into both synthetic medium and serum. One of these compounds has an association constant for iron similar to that of transferrin. Both transferrin and ethylenediamine-di-o-hydroxyphenyl acetic acid (EDDA), which have very high affinities for ferric iron, induced catechol synthesis in growing cultures of strain O111. This organism was inhibited by normal horse serum. Further work showed that traces of specific antibody inhibited catechol synthesis by O111 exposed to EDDA; therefore, the existence of this inhibitory process means that the organism can no longer obtain Fe(3+), which all remains bound to transferrin in serum. In vivo, the inhibition of O111 is similar to that produced by serum in vitro. Neither phagocytosis nor killing by complement appeared to be of any significance during the first 4 h of the infections. Significantly, the purified catechol was capable of abolishing bacteriostasis in vivo. Since these results show that the production of iron-binding catechols is essential for rapid bacterial growth both in vitro and in vivo, these compounds should therefore be considered as true virulence factors. Conversely, any interference by the host with the production or activity of these compounds would constitute an important aspect of antibacterial defense.
先前的工作表明，能够在血清中快速生长的毒性细菌，必须具备一种从其转铁蛋白复合物中去除铁的特定机制。为此，我们对两株大肠杆菌菌株进行了研究。菌株 O141 在血清中具有接种依赖性生长，并且在小鼠腹膜中繁殖，它将铁结合儿茶酚分泌到合成培养基和血清中。这些化合物之一与转铁蛋白的铁结合常数相似。转铁蛋白和乙二胺二邻羟苯乙酸（EDDA）对三价铁具有非常高的亲和力，这两种物质都能诱导菌株 O111 的生长培养物中儿茶酚的合成。这种生物被正常马血清所抑制。进一步的研究表明，暴露于 EDDA 的 O111 中的儿茶酚合成受到特定抗体的微量抑制；因此，这种抑制过程的存在意味着该生物不能再获得 Fe(3+)，所有 Fe(3+) 仍然与血清中的转铁蛋白结合。在体内，O111 的抑制作用与体外血清产生的抑制作用相似。在感染的前 4 小时内，吞噬作用或补体杀伤似乎都没有任何意义。重要的是，纯化的儿茶酚能够在体内消除抑菌作用。由于这些结果表明，铁结合儿茶酚的产生对于体外和体内快速细菌生长是必不可少的，因此这些化合物应被视为真正的毒力因子。相反，宿主对这些化合物的产生或活性的任何干扰都将构成抗菌防御的一个重要方面。
