Albumin Neutralizes Hydrophobic Toxins and Modulates Candida albicans Pathogenicity.
Albumin Neutralizes Hydrophobic Toxins and Modulates Candida albicans Pathogenicity.
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DOI：
10.1128/mbio.00531-21
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发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Gresnigt MS
中科院分区：
文献类型：
--
作者：
Austermeier S;Pekmezović M;Porschitz P;Lee S;Kichik N;Moyes DL;Ho J;Kotowicz NK;Naglik JR;Hube B;Gresnigt MS
白蛋白在血清中含量丰富，但也在粘膜表面分泌，并在炎症增加血管通透性时进入组织。宿主相关的机会致病菌在过敏症期间和引起感染时遇到白蛋白。考虑到白蛋白的普遍存在，我们研究了其在模型人类真菌病原体白色念珠菌感染的发病机制中的作用。白蛋白被引入各种体外模型中，模拟系统性或粘膜念珠菌病的不同阶段，在这些模型中，白蛋白降低了C。白色念珠菌破坏宿主细胞。两亲性毒素candidalysin介导C.白色念珠菌。使用细胞和生物物理测定，我们确定白蛋白的功能通过中和念珠菌溶解素通过疏水相互作用。我们发现，白蛋白，同样，可以中和各种真菌（α-鹅膏蕈碱），细菌（链球菌溶血素O和星形孢菌素），和昆虫（蜂毒肽）疏水毒素。这些数据表明，白蛋白作为一种防御机制，对毒素，这可以发挥作用的微生物感染的发病机制。
Albumin is abundant in serum but is also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic pathogens encounter albumin during commensalism and when causing infections. Considering the ubiquitous presence of albumin, we investigated its role in the pathogenesis of infections with the model human fungal pathogen, Candida albicans. Albumin was introduced in various in vitro models that mimic different stages of systemic or mucosal candidiasis, where it reduced the ability of C. albicans to damage host cells. The amphipathic toxin candidalysin mediates necrotic host cell damage induced by C. albicans. Using cellular and biophysical assays, we determined that albumin functions by neutralizing candidalysin through hydrophobic interactions. We discovered that albumin, similarly, can neutralize a variety of fungal (α-amanitin), bacterial (streptolysin O and staurosporin), and insect (melittin) hydrophobic toxins. These data suggest albumin as a defense mechanism against toxins, which can play a role in the pathogenesis of microbial infections.