Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans.
Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans.
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DOI：
10.1111/cmi.13378
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发表时间：
2021-10
影响因子：
3.4
通讯作者：
Hube B
中科院分区：
文献类型：
--
作者：
Mogavero S;Sauer FM;Brunke S;Allert S;Schulz D;Wisgott S;Jablonowski N;Elshafee O;Krüger T;Kniemeyer O;Brakhage AA;Naglik JR;Dolk E;Hube B
人类致病真菌白色念珠菌是粘膜感染的常见原因。虽然从酵母转变为菌丝形态的能力对于毒力是必不可少的，但菌丝形成和宿主细胞侵入本身不足以诱导上皮损伤。相反，菌丝相关的肽毒素，念珠菌，一种产品的Ece1多蛋白，是关键的破坏因素。虽然人工合成的外源性念珠菌溶解素足以损伤上皮细胞，但损伤程度达不到与入侵的念珠菌相同的水平。白色念珠菌菌丝因此，我们假设需要真菌属性的组合才能将念珠菌溶素递送到入侵口袋，以充分发挥念珠菌的破坏潜力。白色念珠菌感染。利用C.白念珠菌突变株与已知的毒力缺陷，我们证明了充分的损害潜力的C。白色念珠菌需要协调地将念珠菌溶解素递送至侵袭袋。这一过程需要适当的上皮粘附，菌丝的延伸和入侵，高水平的ECE1转录，适当的ECE1加工和分泌的念珠菌。为了确认念珠菌溶素递送，我们产生了对念珠菌溶素特异性的骆驼VHH（纳米抗体），并证明毒素仅在C.白色念珠菌引起的侵入囊。总之，一个明确的毒力属性和细胞过程的组合是至关重要的提供念珠菌溶素的入侵口袋，使充分的损害潜力的C。粘膜感染时出现白色念珠菌。
The human pathogenic fungus Candida albicans is a frequent cause of mucosal infections. Although the ability to transition from the yeast to the hypha morphology is essential for virulence, hypha formation and host cell invasion per se are not sufficient for the induction of epithelial damage. Rather, the hypha-associated peptide toxin, candidalysin, a product of the Ece1 polyprotein, is the critical damaging factor. While synthetic, exogenously added candidalysin is sufficient to damage epithelial cells, the level of damage does not reach the same level as invading C. albicans hyphae. Therefore, we hypothesized that a combination of fungal attributes is required to deliver candidalysin to the invasion pocket to enable the full damaging potential of C. albicans during infection. Utilizing a panel of C. albicans mutants with known virulence defects, we demonstrate that the full damage potential of C. albicans requires the coordinated delivery of candidalysin to the invasion pocket. This process requires appropriate epithelial adhesion, hyphal extension and invasion, high levels of ECE1 transcription, proper Ece1 processing, and secretion of candidalysin. To confirm candidalysin delivery, we generated camelid VHHs (nanobodies) specific for candidalysin, and demonstrate localization and accumulation of the toxin only in C. albicans-induced invasion pockets. In summary, a defined combination of virulence attributes and cellular processes is critical for delivering candidalysin to the invasion pocket to enable the full damage potential of C. albicans during mucosal infection.
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白色念珠菌的菌丝取向受钙依赖性机制调节。
影响因子：
9.2
作者：
Brand, Alexandra;Shanks, Scott;Duncan, Vanessa M. S.;Yang, Meng;Mackenzie, Kevin;Gow, Neil A. R.
通讯作者：
Gow, Neil A. R.
影响因子：
5.4
作者：
Naglik JR;König A;Hube B;Gaffen SL
通讯作者：
Gaffen SL
影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
4.8
作者：
Newport, G;Agabian, N
通讯作者：
Agabian, N
影响因子：
3.7
作者：
Martin R;Moran GP;Jacobsen ID;Heyken A;Domey J;Sullivan DJ;Kurzai O;Hube B
通讯作者：
Hube B