Impact of Endogenous Pneumococcal Hydrogen Peroxide on the Activity and Release of Pneumolysin.
Impact of Endogenous Pneumococcal Hydrogen Peroxide on the Activity and Release of Pneumolysin.
复制标题
DOI：
10.3390/toxins15100593
复制
发表时间：
2023-09-30
期刊：
影响因子：
4.2
通讯作者：
Mraheil MA
中科院分区：
文献类型：
--
作者：
Bazant J;Ott B;Hudel M;Hain T;Lucas R;Mraheil MA
肺炎链球菌是社区获得性肺炎的主要原因。致孔的胆固醇依赖性溶细胞素（CDC）、肺炎球菌溶血素（Pneumolysin，Pneumolysin）和生理代谢产物过氧化氢（H_2O_2）能显著增强肺炎球菌的毒力。虽然大多数研究都集中在两种毒力因子对肺炎球菌感染过程的贡献上，但尚不清楚H2 O2是否或如何影响肺炎球菌的活性。注意，S。肺炎克雷伯氏菌利用内源性H2 O2作为细胞内信号分子来调节几种蛋白质的活性。在这里，我们表明，H2 O2产生负面影响的溶血活性的浓度依赖性的方式。在将毒素中独特且高度保守的半胱氨酸残基取代为丝氨酸后，防止半胱氨酸依赖性亚磺酰化显著降低了毒素对H2 O2处理的敏感性，并完全消除了DTT激活毒素的能力。我们还检测到内源性H2 O2的产生和释放之间的一个明确的逐步相关性，减少H2 O2的生产造成的下降，在释放的H2O。野生型S. pneumoniae菌株和三个突变体在H2 O2产生中受损表明参与肽聚糖（PG）合成和胆碱结合蛋白（CPB）产生的几个基因的表达增强。H2 O2对β-内酰胺释放影响的一种解释是观察到PG桥形成丙氨酰转移酶MurM和MurN的上调，这明显对β-内酰胺释放产生负面影响。我们的研究结果阐明了内源性肺炎球菌H2 O2在控制肺炎球菌活性和释放中的意义。
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. The pore-forming cholesterol-dependent cytolysin (CDC) pneumolysin (PLY) and the physiological metabolite hydrogen peroxide (H2O2) can greatly increase the virulence of pneumococci. Although most studies have focused on the contribution of both virulence factors to the course of pneumococcal infection, it is unknown whether or how H2O2 can affect PLY activity. Of note, S. pneumoniae exploits endogenous H2O2 as an intracellular signalling molecule to modulate the activity of several proteins. Here, we demonstrate that H2O2 negatively affects the haemolytic activity of PLY in a concentration-dependent manner. Prevention of cysteine-dependent sulfenylation upon substitution of the unique and highly conserved cysteine residue to serine in PLY significantly reduces the toxin’s susceptibility to H2O2 treatment and completely abolishes the ability of DTT to activate PLY. We also detect a clear gradual correlation between endogenous H2O2 generation and PLY release, with decreased H2O2 production causing a decline in the release of PLY. Comparative transcriptome sequencing analysis of the wild-type S. pneumoniae strain and three mutants impaired in H2O2 production indicates enhanced expression of several genes involved in peptidoglycan (PG) synthesis and in the production of choline-binding proteins (CPBs). One explanation for the impact of H2O2 on PLY release is the observed upregulation of the PG bridge formation alanyltransferases MurM and MurN, which evidentially negatively affect the PLY release. Our findings shed light on the significance of endogenous pneumococcal H2O2 in controlling PLY activity and release.
登录
查看更多内容
影响因子：
6.7
作者：
Greene NG;Narciso AR;Filipe SR;Camilli A
通讯作者：
Camilli A
RhoA S-亚硝基化作为调节机制影响内皮屏障功能以响应 G-细菌毒素。
影响因子：
5.8
作者：
Chen F;Wang Y;Rafikov R;Haigh S;Zhi WB;Kumar S;Doulias PT;Rafikova O;Pillich H;Chakraborty T;Lucas R;Verin AD;Catravas JD;She JX;Black SM;Fulton DJR
通讯作者：
Fulton DJR
DOI：
10.1016/j.bbalip.2010.06.004
发表时间：
2010-09-01
影响因子：
4.8
作者：
Benisty, Rachel;Cohen, Aharon Yehonatan;Porat, Nurith
通讯作者：
Porat, Nurith
影响因子：
4.2
作者：
Bryant, Joseph C.;Dabbs, Ridge C.;Thornton, Justin A.
通讯作者：
Thornton, Justin A.
DOI：
10.1099/00221287-101-2-237
发表时间：
1977-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
JOHNSON, MK;AULTMAN, KS
通讯作者：
AULTMAN, KS