The streptococcal iron uptake (Siu) transporter is required for iron uptake and virulence in a zebrafish infection model.
The streptococcal iron uptake (Siu) transporter is required for iron uptake and virulence in a zebrafish infection model.
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DOI：
10.1099/mic.0.28075-0
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发表时间：
2005-11
期刊：
影响因子：
1.5
通讯作者：
Griselle E Montañez;M. Neely;Z. Eichenbaum
中科院分区：
文献类型：
--
作者：
Griselle E Montañez;M. Neely;Z. Eichenbaum
对化脓性链球菌的铁摄取机制了解有限，这是一种溶血性人类病原体，除了铁和亚铁之外，还能使用各种血液蛋白。本研究描述了一种名为SIU(链球菌铁摄取)的转运蛋白，它由一个ATP结合蛋白(SIuA)、一个底物结合蛋白(SIUD)和两个膜渗透酶亚基(SiuBG)组成。构建了siuG突变体，并对其进行了鉴定。与亲本菌株相比，突变株在含有血液、血红蛋白或血清形式的铁的复杂介质中生长减慢。在含铁的培养液中，只观察到siuG突变体的生长有轻微的下降。然而，在铁摄取分析中，siuG突变体对Fe3+的掺入减少了约30%。在培养液中加入6微米血红素可抑制野生型对Fe3+的吸收达76%，而添加原卟啉IX则不能，这表明利用血红素作为铁源是抑制Fe3+吸收的原因。SiuG的失活适度降低了Hem抑制细胞掺入Fe3+的能力。失活SIAb(编码第二个铁转运体的膜渗透酶)有类似的结果，两个转运体的失活具有累积效应。这些观察结果表明，SIU和SIA转运蛋白都与链霉菌对血红素的利用有关。化脓性。斑马鱼感染模型的研究表明，siuG突变体在肌肉和腹膜内感染途径中都减弱了。综上所述，这些观察结果表明，SIU系统是Strep中获取铁的途径。在体外和体内都很重要的化脓性细菌。
A limited understanding of iron uptake mechanisms is available for Streptococcus pyogenes, a haemolytic human pathogen capable of using a variety of haemoproteins in addition to ferric and ferrous iron. This study characterizes a transporter named siu (for streptococcal iron uptake), which consists of an ATP-binding protein (SiuA), a substrate-binding protein (SiuD), and two membrane permease subunits (SiuBG). An siuG mutant was constructed and characterized. The mutant demonstrated growth reduction in comparison to the parent strain when grown in complex medium containing iron in the form of blood, haemoglobin or serum. Only a small reduction in the growth of the siuG mutant was observed in medium containing ferric iron. However, in iron uptake assays the siuG mutant showed a decrease of approximately 30 % in Fe3+ incorporation. Addition of 6 microM haem to the medium inhibited Fe3+ uptake by the wild-type by 76 %, while addition of protoporphyrin IX did not, suggesting that utilization of haem as an iron source is responsible for the inhibition of Fe3+ uptake. Inactivation of siuG moderately reduced the ability of haem to inhibit Fe3+ incorporation by the cells. Inactivation of siaB (encoding a membrane permease of a second iron transporter) had a similar outcome, and inactivation of both transporters had a cumulative effect. These observations implicate both the siu and sia transporters in haem utilization by Strep. pyogenes. Studies in a zebrafish infection model revealed that the siuG mutant was attenuated in both intramuscular and intraperitoneal routes of infection. Together these observations show that the siu system is an iron acquisition pathway in Strep. pyogenes that is important both in vitro and in vivo.