Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.

中文翻译：

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细胞壁黑色素通过螯合钙来阻碍新型隐球菌多糖胶囊的生长


新型隐球菌已成为致命真菌病原体中的领跑者，对于许多免疫力低下的 HIV 感染者来说尤其危及生命。多种毒力因子有助于新型隐球菌在人类宿主内的生长和存活，其中最突出的两个是多糖胶囊和黑色素。由于这两个特征都与细胞壁有关，因此我们有兴趣探索这两个毒力因子之间可能的合作或竞争相互作用。虽然胶囊厚度对细胞黑化的速度没有影响，但黑色素色素层的积累导致伴随多糖物质的损失，使黑素化细胞的胶囊比非黑素化细胞薄得多。当黑色素外源性提供给 transwell 培养系统中的细胞时，我们观察到对胶囊生长和维持的类似抑制。我们的结果表明，黑色素会螯合钙，从而限制其在外胶囊组装所需的多糖亚基之间形成二价桥的可用性。黑色素化细胞将输出的多糖掺入生长胶囊的能力降低与脱落多糖的数量相关，这可能对宿主免疫反应产生深远的负面影响。