Brown J S, Gilliland S M, Holden D W
Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Mol Microbiol. 2001 May;40(3):572-85. doi: 10.1046/j.1365-2958.2001.02414.x.
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.
铁的可利用性受限是病原菌在感染过程中生长和存活的主要障碍。与革兰氏阴性病原菌不同，对于革兰氏阳性病原菌如何获取这种必需金属知之甚少。我们已鉴定出肺炎链球菌的两个基因座pit1和pit2，它们编码该生物体摄取铁所需的ABC铁转运蛋白的同源物。含有pit1或pit2缺失拷贝的肺炎链球菌菌株对铁依赖性抗生素链黑菌素的敏感性降低，而同时含有pit1和pit2缺失拷贝的菌株无法将血红蛋白用作铁源且铁摄取速率降低。在肺部和全身感染的小鼠模型中，pit2缺失菌株的毒力中度减弱，pit1 / pit2缺失菌株的毒力强烈减弱，表明pit基因座在肺炎链球菌的体内生长过程中起关键作用。pit2基因座位于一个27 kb的染色体DNA区域内，该区域具有革兰氏阴性细菌致病岛的几个特征。这个可能的致病岛（PPI-1）是首次针对肺炎链球菌进行描述，其获得可能在这种重要人类病原体的进化中发挥了重要作用。
