Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci
Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci
复制标题
非血红素含铁铁蛋白 Dpr 对肺炎球菌应激反应和毒力的影响
DOI：
10.1128/iai.01829-14
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发表时间：
2014-09-01
影响因子：
3.1
通讯作者：
Lu, Ying-Jie p
中科院分区：
文献类型：
--
作者：
Hua, Chun-Zhen;Howard, Angela;Lu, Ying-Jie p
摘要肺炎链球菌（肺炎球菌）产生过氧化氢作为代谢的副产品，并提供了一个竞争优势，对共定植细菌。由于肺炎球菌不产生过氧化氢酶或过氧化氢的诱导调节剂，因此对过氧化氢的抗性机制尚不清楚。在其他链球菌中负责抵抗过氧化氢和铁的基因是编码非血红素含铁铁蛋白（dpr）的基因，但以前试图通过产生dpr突变体来研究肺炎球菌中的该基因是不成功的。在目前的研究中，我们发现dpr与下游基因dhfr和clpX在操纵子中。我们产生了一个dpr缺失突变体，在细菌培养基中显示正常的对数生长期早期和中期，但在稳定期存活不太好;加入过氧化氢酶部分挽救了生长缺陷。我们发现，dpr突变体是显着更敏感的pH值，热，铁浓度，和氧化应激，由于过氧化氢。使用小鼠模型的殖民，我们也表明，dpr突变体显示出降低的殖民能力，并更迅速地从鼻咽清除。因此，我们的研究结果表明，DPR是重要的肺炎球菌耐压力和鼻咽定植。
ABSTRACT Streptococcus pneumoniae (pneumococcus) produces hydrogen peroxide as a by-product of metabolism and provides a competitive advantage against cocolonizing bacteria. As pneumococci do not produce catalase or an inducible regulator of hydrogen peroxide, the mechanism of resistance to hydrogen peroxide is unclear. A gene responsible for resistance to hydrogen peroxide and iron in other streptococci is that encoding nonheme iron-containing ferritin, dpr, but previous attempts to study this gene in pneumococcus by generating a dpr mutant were unsuccessful. In the current study, we found that dpr is in an operon with the downstream genes dhfr and clpX. We generated a dpr deletion mutant which displayed normal early-log-phase and mid-log-phase growth in bacteriologic medium but survived less well at stationary phase; the addition of catalase partially rescued the growth defect. We showed that the dpr mutant is significantly more sensitive to pH, heat, iron concentration, and oxidative stress due to hydrogen peroxide. Using a mouse model of colonization, we also showed that the dpr mutant displays a reduced ability to colonize and is more rapidly cleared from the nasopharynx. Our results thus suggest that Dpr is important for pneumococcal resistance to stress and for nasopharyngeal colonization.