Brown Jeremy S, Gilliland Sarah M, Ruiz-Albert Javier, Holden David W
Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Medicine, London SW7 2AZ, United Kingdom.
Infect Immun. 2002 Aug;70(8):4389-98. doi: 10.1128/IAI.70.8.4389-4398.2002.
Bacteria frequently have multiple mechanisms for acquiring iron, an essential micronutrient, from the environment. We have identified a four-gene Streptococcus pneumoniae operon, named pit, encoding proteins with similarity to components of a putative Brachyspira hyodysenteriae iron uptake ABC transporter, Bit. An S. pneumoniae strain containing a defined mutation in pit has impaired growth in medium containing the iron chelator ethylenediamine di-o-hydroxyphenylacetic acid, reduced sensitivity to the iron-dependent antibiotic streptonigrin, and impaired virulence in a mouse model of S. pneumoniae systemic infection. Furthermore, addition of a mutation in pit to a strain containing mutations in the two previously described S. pneumoniae iron uptake ABC transporters, piu and pia, resulted in a strain with impaired growth in two types of iron-deficient medium, a high degree of resistance to streptonigrin, and a reduced rate of iron uptake. Comparison of the susceptibilities to streptonigrin of the individual pit, piu, and pia mutant strains and comparison of the growth in iron-deficient medium and virulence of single and double mutant strains suggest that pia is the dominant iron transporter during in vitro and in vivo growth.
细菌通常具有多种从环境中获取铁(一种必需的微量营养素)的机制。我们鉴定出一个名为pit的肺炎链球菌四基因操纵子,其编码的蛋白质与一种假定的猪痢疾短螺旋体铁摄取ABC转运蛋白Bit的组分相似。在pit中含有特定突变的肺炎链球菌菌株,在含有铁螯合剂乙二胺二邻羟基苯乙酸的培养基中生长受损,对铁依赖性抗生素链黑菌素的敏感性降低,并且在肺炎链球菌全身感染的小鼠模型中毒力受损。此外,在含有先前描述的两种肺炎链球菌铁摄取ABC转运蛋白piu和pia突变的菌株中添加pit突变,产生了一种在两种缺铁培养基中生长受损、对链黑菌素有高度抗性且铁摄取速率降低的菌株。对单个pit、piu和pia突变菌株对链黑菌素的敏感性进行比较,以及对单突变和双突变菌株在缺铁培养基中的生长和毒力进行比较,表明pia是体外和体内生长过程中的主要铁转运蛋白。