A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence
A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence
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DOI：
10.1046/j.1365-2958.2001.02414.x
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发表时间：
2001-05-01
影响因子：
3.6
通讯作者：
Holden, DW
中科院分区：
文献类型：
--
作者：
Brown, JS;Gilliland, SM;Holden, DW
受限制的铁供应是病原菌在感染期间生长和存活的主要障碍。与革兰氏阴性病原体相比，人们对革兰氏阳性病原体如何获得这种必需金属知之甚少。我们已经确定了两个肺炎链球菌的遗传位点，pit1和pit2，它们编码ABC铁转运蛋白的同源物，而ABC铁转运蛋白是肺炎链球菌吸收铁所必需的。含有pit1或pit2断裂拷贝的肺炎链球菌菌株对铁依赖性抗生素链黑素的敏感性降低，含有pit1和pit2断裂拷贝的菌株不能利用血红蛋白作为铁源，并且铁摄取率降低。在肺部和全身感染小鼠模型中，pit2（-）菌株的毒力较弱，而pit1(-)/pit2（-）菌株的毒力较弱，表明pit位点在肺炎链球菌体内生长过程中起着关键作用。pit2位点位于染色体DNA的一个27kb区域内，该区域具有革兰氏阴性细菌致病性岛的几个特征。这种可能的致病性岛（PPI-1）是首次被描述为肺炎链球菌，它的获得可能在这种重要的人类病原体的进化中发挥了重要作用。
Restricted iron availability is a major obstacle to growth and survival of pathogenic bacteria during infection. In contrast to Gram-negative pathogens, little is known about how Gram-positive pathogens obtain this essential metal. We have identified two Streptococcus pneumoniae genetic loci, pit1 and pit2, encoding homologues of ABC iron transporters that are required for iron uptake by this organism. S. pneumoniae strains containing disrupted copies of either pit1 or pit2 had decreased sensitivity to the iron-dependent antibiotic streptonigrin, and a strain containing disrupted copies of both pit1 and pit2 was unable to use haemoglobin as an iron source and had a reduced rate of iron uptake. The pit2(-) strain was moderately and the pit1(-)/pit2(-) strain strongly attenuated in virulence in mouse models of pulmonary and systemic infection, showing that the pit loci play a critical role during in vivo growth of S. pneumoniae. The pit2 locus is contained within a 27 kb region of chromosomal DNA that has several features of Gram-negative bacterial pathogenicity islands. This probable pathogenicity island (PPI-1) is the first to be described for S. pneumoniae, and its acquisition is likely to have played a significant role in the evolution of this important human pathogen.