Effects of iron deprivation on Mycobacterium avium growth
Effects of iron deprivation on Mycobacterium avium growth
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DOI：
10.1054/tuld.1999.0216
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发表时间：
1999-01-01
期刊：
影响因子：
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通讯作者：
Appelberg, R.
中科院分区：
文献类型：
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作者：
Gomes, M. S.;Dom, G.;Appelberg, R.
设定：获得性免疫缺陷综合征（AIDS）患者在不同组织中的铁沉积增加，这可能有利于鸟分枝杆菌的生长，鸟分枝杆菌是这些患者中常见的细菌机会主义者。目的：检测体内外降低巨噬细胞铁负荷是否能降低M。鸟类增殖设计图：在体外无菌培养基或培养的巨噬细胞中以及在操纵铁状态后在小鼠体内评价分枝杆菌增殖。结果如下：去铁胺（DFO）、N，N ′-双（2-羟基苄基）乙二胺-N，N ′-二乙酸（HBED）和1-氨基-3-（2-联吡啶）异喹啉衍生物（VUF 8514）对M.在无菌培养基中培养。DFO和HBED对M.而VUF 8514的使用由于其对宿主细胞的毒性而被阻止。DFO和HBED均能增强干扰素γ诱导的骨髓源性巨噬细胞的抑菌作用。在体内，缺铁饮食导致M。而DFO或HBED的腹腔内给药对小鼠的铁状态影响很小，因此影响很小。结论：铁抑制是一种抑制巨噬细胞生长的方法。avium体外实验数据表明，铁螯合化合物可能是有用的辅助治疗对M。avium，一旦它们的体内活性被优化。
Setting: Acquired immune deficiency syndrome (AIDS) patients have increased iron deposition in different tissues which may favour the growth of Mycobacterium avium, a common bacterial opportunist in these patients. Objective: To test whether reducing the iron loads in macrophages in vitro and in vivo reduces M. avium proliferation. Design: Mycobacterial proliferation was evaluated in vitro either in axenic media or cultured macrophages and in vivo in mice after manipulation of the iron status. Results: Three different compounds - desferrioxamine (DFO), N,N'bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and a 1-amino-3-(2-bipyridyl)isoquinoline derivative (VUF8514) - were found to inhibit the growth of M. avium in axenic medium. DFO and HBED were also active in inhibiting the intramacrophagic growth of M. avium, while the use of VUF8514 was prevented by its toxicity towards the host cell. Both DFO and HBED enhanced the mycobacteriostatic effect induced in bone marrow derived macrophages by interferon gamma. In vivo, an iron poor diet led to reduced M. avium proliferation whereas the intraperitoneal administration of either DFO or HBED had small effects as they impacted little on the iron status of mice. Conclusion: these results confirm that iron withholding is a means of inhibiting the growth of M. avium. In vitro data suggest that iron chelating compounds may be useful as adjunct therapy against M. avium, once their in vivo activity is optimized.