Sideromycins: tools and antibiotics.
Sideromycins: tools and antibiotics.
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DOI：
10.1007/s10534-008-9199-7
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发表时间：
2009-02
期刊：
影响因子：
3.5
通讯作者：
Bohn, Erwin
中科院分区：
文献类型：
--
作者：
Braun, Volkmar;Pramanik, Avijit;Gwinner, Thomas;Koeberle, Martin;Bohn, Erwin
铁霉素是一种与铁载体共价连接的抗生素。它们被主动运送到革兰氏阳性和革兰氏阴性细菌中。通过外膜和细胞质膜的能量耦合运输可大大提高其抗生素效率；它们的最低抑制浓度至少比通过扩散进入细胞的抗生素低100倍。这与革兰氏阴性菌特别相关，因为通常形成渗透性屏障的外膜在这种情况下积极促进铁霉素的吸收。铁霉素耐药突变体可用于鉴定铁载体运输系统，因为突变通常发生在运输基因中。这里讨论两种铁霉素，白霉素和沙霉素。白霉素是铁铬的衍生物，具有结合的硫核糖基嘧啶部分，可抑制seryl-t-RNA合成酶。沙霉素是一种与氨基双糖结合的铁胺衍生物，可能抑制蛋白质合成。已经确定了与外膜转运蛋白FhuA和质周结合蛋白FhuD结合的白霉素晶体结构。Albomycin和salmycin分别被用来表征大肠杆菌、肺炎链球菌和金黄色葡萄球菌的运输系统。在使用小肠结肠炎耶尔森菌、肺炎链球菌和金黄色葡萄球菌感染的小鼠模型中，研究了白霉素和沙霉素的体内疗效。Albomycin在清除感染方面是有效的，而salmycin太不稳定，不能导致细菌数量的大量减少。白霉素抗性突变体的恢复率低于野生型，这表明突变体的适应度降低。如果能从链菌中分离或化学合成足够数量的霉素，那么它可能是一种有用的抗生素。
Sideromycins are antibiotics covalently linked to siderophores. They are actively transported into gram-positive and gram-negative bacteria. Energy-coupled transport across the outer membrane and the cytoplasmic membrane strongly increases their antibiotic efficiency; their minimal inhibitory concentration is at least 100-fold lower than that of antibiotics that enter cells by diffusion. This is particularly relevant for gram-negative bacteria because the outer membrane, which usually forms a permeability barrier, in this case actively contributes to the uptake of sideromycins. Sideromycin-resistant mutants can be used to identify siderophore transport systems since the mutations are usually in transport genes. Two sideromycins, albomycin and salmycin, are discussed here. Albomycin, a derivative of ferrichrome with a bound thioribosyl-pyrimidine moiety, inhibts seryl-t-RNA synthetase. Salmycin, a ferrioxamine derivative with a bound aminodisaccharide, presumably inhibts protein synthesis. Crystal structures of albomycin bound to the outer membrane transporter FhuA and the periplasmic binding protein FhuD have been determined. Albomycin and salmycin have been used to characterize the transport systems of Escherichia coli and Streptococcus pneumoniae and of Staphylococcus aureus, respectively. The in vivo efficacy of albomycin and salmycin has been examined in a mouse model using Yersinia enterocolitica, S. pneumoniae, and S. aureus infections. Albomycin is effective in clearing infections, whereas salmycin is too unstable to lead to a large reduction in bacterial numbers. The recovery rate of albomycin-resistant mutants is lower than that of the wild-type, which suggests a reduced fitness of the mutants. Albomycin could be a useful antibiotic provided sufficient quantities can be isolated from streptomycetes or synthesized chemically.
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影响因子：
3.6
作者：
BRAUN, V;HERRMANN, C
通讯作者：
HERRMANN, C
影响因子：
4.9
作者：
CURTIS, NAC;EISENSTADT, RL;WHITE, AJ
通讯作者：
WHITE, AJ
DOI：
10.1111/j.1432-1033.1979.tb13283.x
发表时间：
1979-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
HARTMANN, A;FIEDLER, HP;BRAUN, V
通讯作者：
BRAUN, V
影响因子：
3.5
作者：
Krewulak, KD;Shepherd, CM;Vogel, HJ
通讯作者：
Vogel, HJ
影响因子：
3.2
作者：
SCHULTZHAUSER, G;KOSTER, W;BRAUN, V
通讯作者：
BRAUN, V