Department of Sciences, Roma Tre University, Roma, Italy.
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Front Immunol. 2020 Dec 8;11:507092. doi: 10.3389/fimmu.2020.507092. eCollection 2020.
The pathogenicity of group A (GAS) is mediated by direct bacterial invasivity and toxin-associated damage. Among the extracellular products, the exotoxin streptolysin O (SLO) is produced by almost all GAS strains. SLO is a pore forming toxin (PFT) hemolitically active and extremely toxic . Recent evidence suggests that human serum albumin (HSA), the most abundant protein in plasma, is a player in the innate immunity "orchestra." We previously demonstrated that HSA acts as a physiological buffer, partially neutralizing toxins that reach the bloodstream after being produced in the colon. Here, we report the and capability of HSA to neutralize the cytotoxic and hemolytic effects of SLO. HSA binds SLO with high affinity at a non-conventional site located in domain II, which was previously reported to interact also with toxins. HSA:SLO recognition protects HEp-2 and A549 cells from cytotoxic effects and cell membrane permeabilization induced by SLO. Moreover, HSA inhibits the SLO-dependent hemolytic effect in red blood cells isolated from healthy human donors. The recognition of SLO by HSA may have a significant protective role in human serum and sustains the emerging hypothesis that HSA is an important constituent of the innate immunity system.
A 组链球菌（GAS）的致病性是由直接的细菌侵袭和毒素相关的损伤介导的。在细胞外产物中，外毒素链球菌溶血素 O（SLO）几乎由所有 GAS 菌株产生。SLO 是一种形成孔的毒素（PFT），具有溶血活性和极高的毒性。最近的证据表明，人血清白蛋白（HSA）是血浆中最丰富的蛋白质，是先天免疫“管弦乐队”中的一员。我们之前证明 HSA 作为一种生理缓冲剂，部分中和了在结肠中产生后进入血液的毒素。在这里，我们报告了 HSA 中和 SLO 的细胞毒性和溶血作用的能力。HSA 以高亲和力与位于 II 结构域的非传统位点结合 SLO，该位点先前被报道也与 毒素相互作用。HSA:SLO 识别可保护 HEp-2 和 A549 细胞免受 SLO 诱导的细胞毒性和细胞膜通透性。此外，HSA 抑制从健康人类供体分离的红细胞中 SLO 依赖性溶血作用。HSA 对 SLO 的识别可能在人血清中具有重要的保护作用，并支持 HSA 是先天免疫系统的重要组成部分的新兴假说。
