Conserved DegP protease in gram-positive bacteria is essential for thermal and oxidative tolerance and full virulence in Streptococcus pyogenes
Conserved DegP protease in gram-positive bacteria is essential for thermal and oxidative tolerance and full virulence in Streptococcus pyogenes
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DOI：
10.1128/iai.69.9.5538-5545.2001
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发表时间：
2001-09-01
影响因子：
3.1
通讯作者：
Hruby, DE
中科院分区：
文献类型：
--
作者：
Jones, CH;Bolken, TC;Hruby, DE
DegP蛋白酶是一种多功能伴侣和蛋白酶，已被证明对革兰氏阴性病原体（如肠沙门氏菌血清型鼠伤寒沙门氏菌、流产布鲁氏菌、小肠结肠炎耶尔森菌和铜绿假单胞菌）的毒力至关重要。DegP在发病机制中的功能似乎是降解受损蛋白，这些蛋白是由于宿主对感染的初始反应而积累的，其中包括释放活性氧中间体。此外，DegP蛋白酶在监测和维持大肠杆菌外周质中起重要作用，并影响大肠杆菌菌毛的生物发生。我们在此报告了在化脓性链球菌、戈多氏链球菌、变形链球菌、金黄色葡萄球菌和粪肠球菌中高度同源酶的鉴定。此外，在化脓性葡萄球菌中插入失活的degP等位基因的表型与大肠杆菌相似，对生长具有温度敏感性，对活性氧中间体的敏感性增强。在小鼠链球菌感染模型中的毒力研究表明，功能DegP蛋白酶是完全毒力所必需的。这些结果表明，DegP是未来抗感染药物开发的一个有吸引力的广谱靶标。
The DegP protease, a multifunctional chaperone and protease, has been shown to be essential for virulence in gram-negative pathogens such as Salmonella enterica serovar Typhimurium, Brucella abortus, Yersinia enterocolitica, and Pseudomonas aeruginosa. The function of DegP in pathogenesis appears to be the degradation of damaged proteins that accumulate as a result of the initial host response to infection, which includes the release of reactive oxygen intermediates. Additionally, the DegP protease plays a major role in monitoring and maintaining the Escherichia coli periplasm and influences E. coli pilus biogenesis. We report here the identification of highly homologous enzymes in Streptococcus pyogenes, Streptococcus gordonii, Streptococcus mutans, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the phenotype of an insertionally inactivated degP allele in S. pyogenes is similar to that reported for E. coli, with temperature sensitivity for growth and enhanced sensitivity to reactive oxygen intermediates. Virulence studies in a mouse model of streptococcal infection indicate that a functional DegP protease is required for full virulence. These results suggest DegP as an attractive broad-spectrum target for future anti-infective drug development.