Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus.
Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus.
复制标题
DOI：
10.1371/journal.pone.0008557
复制
发表时间：
2010-01-05
期刊：
影响因子：
3.7
通讯作者：
Gallo RL
中科院分区：
文献类型：
--
作者：
Cogen AL;Yamasaki K;Muto J;Sanchez KM;Crotty Alexander L;Tanios J;Lai Y;Kim JE;Nizet V;Gallo RL
抗菌肽在宿主防御病原体方面起着重要作用。近期研究表明，来自表皮葡萄球菌（S. epidermidis）的酚溶性调节蛋白（PSMs）能够与脂质膜相互作用、形成复合物并发挥抗菌活性。鉴于皮肤常驻菌表皮葡萄球菌的数量丰富且无害，我们推测其PSMs有助于宿主防御。在此我们通过免疫组织化学方法表明，表皮葡萄球菌δ毒素（PSMγ）通常存在于人类皮肤的表皮，在真皮中少量存在。合成的δ毒素与中性粒细胞胞外陷阱（NETs）相互作用，并与导管素共定位，同时还能诱导人中性粒细胞形成NETs。在针对A组链球菌（GAS）的抗菌试验中，δ毒素与CRAMP、人β-防御素2（hBD2）和人β-防御素3（hBD3）协同作用。在全血中，添加δ毒素对GAS有抑菌作用，并且在NETs中，δ毒素增强了其对该病原体的杀伤能力。免疫共沉淀和色氨酸光谱分析表明δ毒素与宿主抗菌肽LL - 37、CRAMP、hBD2和hBD3直接结合。最后，在小鼠伤口模型中，当伤口用δ毒素预处理时，GAS的存活率降低（同时Mip - 2细胞因子水平也降低）。因此，这些数据表明，表皮葡萄球菌衍生的δ毒素与先天免疫系统中宿主衍生的抗菌肽协同作用，降低了一种重要的人类细菌病原体的存活率。
Antimicrobial peptides play an important role in host defense against pathogens. Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S. epidermidis) were shown to interact with lipid membranes, form complexes, and exert antimicrobial activity. Based on the abundance and innocuity of the cutaneous resident S. epidermidis, we hypothesized that their PSMs contribute to host defense. Here we show that S. epidermidis δ-toxin (PSMγ) is normally present in the epidermis and sparsely in the dermis of human skin using immunohistochemistry. Synthetic δ-toxin interacted with neutrophil extracellular traps (NETs) and colocalized with cathelicidin while also inducing NET formation in human neutrophils. In antimicrobial assays against Group A Streptococcus (GAS), δ-toxin cooperated with CRAMP, hBD2, and hBD3. In whole blood, addition of δ-toxin exerted a bacteriostatic effect on GAS, and in NETs, δ-toxin increased their killing capacity against this pathogen. Coimmunoprecipitation and tryptophan spectroscopy demonstrated direct binding of δ-toxin to host antimicrobial peptides LL-37, CRAMP, hBD2, and hBD3. Finally, in a mouse wound model, GAS survival was reduced (along with Mip-2 cytokine levels) when the wounds were pretreated with δ-toxin. Thus, these data suggest that S. epidermidis–derived δ-toxin cooperates with the host-derived antimicrobial peptides in the innate immune system to reduce survival of an important human bacterial pathogen.
登录
查看更多内容
DOI：
10.1093/protein/8.3.315
发表时间：
1995-03-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
DHOPLE, VM;NAGARAJ, R
通讯作者：
NAGARAJ, R
影响因子：
3.6
作者：
Dorschner, RA;Lin, KH;Gallo, RL
通讯作者：
Gallo, RL
影响因子：
4.1
作者：
Oren, Z;Lerman, JC;Shai, Y
通讯作者：
Shai, Y
影响因子：
64.8
作者：
Nizet, V;Ohtake, T;Gallo, RL
通讯作者：
Gallo, RL
影响因子：
82.9
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
通讯作者：
Brauner, Annelie