Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence
Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence
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DOI：
10.1046/j.1365-2958.2003.03861.x
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发表时间：
2004-01-01
影响因子：
3.6
通讯作者：
Hanna, P
中科院分区：
文献类型：
--
作者：
Cendrowski, S;MacArthur, W;Hanna, P
系统性炭疽感染可以被表征为分阶段进行，从吞噬细胞内的早期细胞内建立阶段开始，随后是涉及大量菌血症、脓毒症和死亡的细胞外阶段。因为大多数细菌需要铁，而宿主通过体内平衡机制限制铁的可用性，我们假设B。炭疽菌在其生长阶段需要高亲和力的铁获取机制。鉴定了两种推定类型的铁载体合成操纵子，命名为炭疽芽孢杆菌儿茶酚，bac（anthrabactin）和炭疽铁载体生物合成，asb（anthrachelin）。在B中产生了蒽环菌素和蒽环菌素途径中的定向基因缺失。炭疽（Sterne）34F2背景导致asbA和bacCEBF突变。在DeltaasbA和DeltabacCEBF菌株的铁耗尽生长期间观察到铁载体产生的减少，但在这些条件下，仅DeltaasbA菌株的生长减弱。此外，DeltaasbA菌株在巨噬细胞（MPhi）中的生长和小鼠中的毒力均严重减毒。相比之下，DeltabacCEBF菌株与亲本菌株在表型上没有差异。这些研究结果支持在炭疽的细胞内阶段铁同化需要anthrachelin而不是anthracbactin。
Systemic anthrax infections can be characterized as proceeding in stages, beginning with an early intracellular establishment stage within phagocytes that is followed by extracelluar stages involving massive bacteraemia, sepsis and death. Because most bacteria require iron, and the host limits iron availability through homeostatic mechanisms, we hypothesized that B. anthracis requires a high-affinity mechanism of iron acquisition during its growth stages. Two putative types of siderophore synthesis operons, named Bacillus anthracis catechol, bac (anthrabactin), and anthrax siderophore biosynthesis, asb (anthrachelin), were identified. Directed gene deletions in both anthrabactin and anthrachelin pathways were generated in a B. anthracis (Sterne) 34F2 background resulting in mutations in asbA and bacCEBF. A decrease in siderophore production was observed during iron-depleted growth in both the DeltaasbA and DeltabacCEBF strains, but only the DeltaasbA strain was attenuated for growth under these conditions. In addition, the DeltaasbA strain was severely attenuated both for growth in macrophages (MPhi) and for virulence in mice. In contrast, the DeltabacCEBF strain did not differ phenotypically from the parental strain. These findings support a requirement for anthrachelin but not anthrabactin in iron assimilation during the intracellular stage of anthrax.