Antimicrobial action of calprotectin that does not involve metal withholding.
Antimicrobial action of calprotectin that does not involve metal withholding.
复制标题
DOI：
10.1039/c8mt00133b
复制
发表时间：
2018-12-12
期刊：
影响因子：
--
通讯作者：
Culotta VC
中科院分区：
文献类型：
--
作者：
Besold AN;Culbertson EM;Nam L;Hobbs RP;Boyko A;Maxwell CN;Chazin WJ;Marques AR;Culotta VC
钙卫蛋白是一种有效的抗微生物剂，通过紧密结合过渡金属如Mn和Zn来抑制病原体的生长，从而防止它们被入侵的微生物摄取和利用。在感染部位，钙卫蛋白从中性粒细胞大量释放，但钙卫蛋白也存在于可能与感染相关的非中性粒细胞类型中。我们在这里表明，在感染莱姆病病原体伯氏疏螺旋体（疏螺旋体）的患者中，钙卫蛋白产生于皮肤的无嗜中性粒细胞区域，在表皮角质形成细胞和浸润真皮的免疫细胞中，包括CD68阳性巨噬细胞。在培养中，B. burgdorferi氏菌的生长受到钙卫蛋白的抑制，但令人惊讶的是，该机制并不涉及传统的金属营养素抑制。B。暴露于钙卫蛋白的burgdorferi细胞停止生长，细胞内Mn没有减少，Mn酶（包括SodA超氧化物歧化酶）的活性没有损失。此外，细胞内锌无明显损失。我们发现钙卫蛋白抑制B而不是金属耗竭。通过需要钙卫蛋白与细菌的物理结合的机制来促进伯氏螺旋体的生长。相比之下，钙卫蛋白抑制E.大肠杆菌生长而不与微生物发生物理相互作用，钙卫蛋白有效地耗尽了大肠杆菌。大肠杆菌胞内Mn和Zn的含量。我们和B一起学习。Burgdorferi证明钙卫蛋白的抗微生物能力是复杂的，并且远远超出了金属微量营养素的简单保留。钙卫蛋白（绿色）的金属（红色）结合形式结合伯氏疏螺旋体并抑制病原体生长，而不抑制金属。
Calprotectin is a potent antimicrobial that inhibits the growth of pathogens by tightly binding transition metals such as Mn and Zn, thereby preventing their uptake and utilization by invading microbes. At sites of infection, calprotectin is abundantly released from neutrophils, but calprotectin is also present in non-neutrophil cell types that may be relevant to infections. We show here that in patients infected with the Lyme disease pathogen Borreliella (Borrelia) burgdorferi, calprotectin is produced in neutrophil-free regions of the skin, in both epidermal keratinocytes and in immune cells infiltrating the dermis, including CD68 positive macrophages. In culture, B. burgdorferi’s growth is inhibited by calprotectin, but surprisingly, the mechanism does not involve the classical withholding of metal nutrients. B. burgdorferi cells exposed to calprotectin cease growth with no reduction in intracellular Mn and no loss in activity of Mn enzymes including the SodA superoxide dismutase. Additionally, there is no obvious loss in intracellular Zn. Rather than metal depletion, we find that calprotectin inhibits B. burgdorferi growth through a mechanism that requires physical association of calprotectin with the bacteria. By comparison, calprotectin inhibited E. coli growth without physically interacting with the microbe, and calprotectin effectively depleted E. coli of intracellular Mn and Zn. Our studies with B. burgdorferi demonstrate that the antimicrobial capacity of calprotectin is complex and extends well beyond simple withholding of metal micronutrients. The metal (red) bound form of calprotectin (green) binds Borrelia burgdorferi and inhibits pathogen growth without metal withholding.
登录
查看更多内容
影响因子：
3.6
作者：
Bourret TJ;Boylan JA;Lawrence KA;Gherardini FC
通讯作者：
Gherardini FC
影响因子：
15
作者：
Brophy MB;Nakashige TG;Gaillard A;Nolan EM
通讯作者：
Nolan EM
影响因子：
4.4
作者：
Akerstrom, Bo;Bjorck, Lars
通讯作者：
Bjorck, Lars
影响因子：
4.4
作者：
Eming, Sabine A.;Koch, Manuel;Fox, Jay W.
通讯作者：
Fox, Jay W.
影响因子：
3.2
作者：
Broome, AM;Ryan, D;Eckert, RL
通讯作者：
Eckert, RL