Streptococcus pyogenes c-di-AMP phosphodiesterase, GdpP, influences SpeB processing and virulence.

Streptococcus pyogenes c-di-AMP phosphodiesterase, GdpP, influences SpeB processing and virulence.
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DOI:
10.1371/journal.pone.0069425
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Kang SO
Kang SO
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cho KH;Kang SO

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小环核苷酸衍生物被原核生物和真核生物用作第二信使,以调节响应各种信号的多种细胞过程。在细菌中,c-di-AMP是最近发现的,并且一些革兰氏阳性病原体包括S。化脓性链球菌使用这种环核苷酸衍生物作为第二信使,而不是c-di-GMP(一种被充分研究的重要细菌第二信使)。GdpP(c-di-AMP phosphodiesterase)是细胞内降解c-di-AMP的一种酶,其在S.尚未检查化脓性链球菌。为了测试GdpP的细胞作用,我们创建了具有gdpP基因的非极性框内缺失的菌株,并检查了该菌株的特性,包括毒力。从这项研究中,我们证明了GdpP影响SpeB的生物合成,主要分泌的半胱氨酸蛋白酶,在翻译后水平,对β内酰胺抗生素氨苄青霉素的敏感性,并在小鼠皮下感染模型中完全毒力是必要的。
Small cyclic nucleotide derivatives are employed as second messengers by both prokaryotes and eukaryotes to regulate diverse cellular processes responding to various signals. In bacteria, c-di-AMP has been discovered most recently, and some Gram-positive pathogens including S. pyogenes use this cyclic nucleotide derivative as a second messenger instead of c-di-GMP, a well-studied important bacterial second messenger. GdpP, c-di-AMP phosphodiesterase, is responsible for degrading c-di-AMP inside cells, and the cellular role of GdpP in S. pyogenes has not been examined yet. To test the cellular role of GdpP, we created a strain with a nonpolar inframe deletion of the gdpP gene, and examined the properties of the strain including virulence. From this study, we demonstrated that GdpP influences the biogenesis of SpeB, the major secreted cysteine protease, at a post-translational level, susceptibility to the beta lactam antibiotic ampicillin, and is necessary for full virulence in a murine subcutaneous infection model.
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