A novel immune evasion strategy of candida albicans: proteolytic cleavage of a salivary antimicrobial peptide.
A novel immune evasion strategy of candida albicans: proteolytic cleavage of a salivary antimicrobial peptide.
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DOI：
10.1371/journal.pone.0005039
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Jabra-Rizk MA
中科院分区：
文献类型：
--
作者：
Meiller TF;Hube B;Schild L;Shirtliff ME;Scheper MA;Winkler R;Ton A;Jabra-Rizk MA
口咽念珠菌病是一种机会性感染，被认为是艾滋病的先兆。病原体白色念珠菌是一种常见于人类粘膜表面的真菌。然而，在免疫功能障碍的情况下，C.白色念珠菌可成为机会性病原体，引起浅表或甚至危及生命的感染。然而，这种转变背后的原因尚不清楚。在口腔中，唾液抗菌肽被认为是宿主先天性防御系统的重要组成部分，在预防微生物定植中起重要作用。组胺素-5特异性地表现出抗C.白色念珠菌。我们以前的研究表明，histatin-5水平显着降低，在唾液中的HIV+个人，表明histatin-5在保持C。白色念珠菌在其发育阶段。C.白念珠菌的致病性是其通过调节毒力决定因子而适应的能力的结果，其中最值得注意的是参与组织降解的蛋白水解酶（Saps）。在这项研究中，我们表明，C。白色念珠菌细胞有效且快速地降解组胺素-5，导致其抗念珠菌效力的丧失。此外，我们还证明了这种细胞活性是由于参与C.白色念珠菌发病机制具体而言，蛋白水解归因于Sap 9，进而将组胺素-5鉴定为该同工酶的第一个宿主特异性底物。这些发现第一次证明了一种特定的C。白念珠菌酶降解和灭活宿主抗微生物肽，该肽参与保护口腔粘膜免受念珠菌感染。从而为研究C. albicans转化的影响因素提供了新的思路。白色念珠菌从真菌到病原体，具有重要的临床意义的替代治疗。本报告描述了自HIV出现以来，HIV+个体对口腔念珠菌病易感性增强的第一个明确机制。
Oropharyngeal candidiasis is an opportunistic infection considered to be a harbinger of AIDS. The etiologic agent Candida albicans is a fungal species commonly colonizing human mucosal surfaces. However, under conditions of immune dysfunction, colonizing C. albicans can become an opportunistic pathogen causing superficial or even life-threatening infections. The reasons behind this transition, however, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 specifically has exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for histatin-5 in keeping C. albicans in its commensal stage. The versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are proteolytic enzymes (Saps), involved in tissue degradation. In this study, we show that C. albicans cells efficiently and rapidly degrade histatin-5, resulting in loss of its anti-candidal potency. In addition, we demonstrate that this cellular activity is due to proteolysis by a member of the secreted aspartic proteases (Sap) family involved in C. albicans pathogenesis. Specifically, the proteolysis was attributed to Sap9, in turn identifying histatin-5 as the first host-specific substrate for that isoenzyme. These findings demonstrate for the first time the ability of a specific C. albicans enzyme to degrade and deactivate a host antimicrobial peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen, with important clinical implications for alternative therapy. This report characterizes the first defined mechanism behind the enhanced susceptibility of HIV+ individuals to oral candidiasis since the emergence of HIV.
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影响因子：
3.1
作者：
DeBernardis, F;Chiani, P;Cassone, A
通讯作者：
Cassone, A
影响因子：
6.4
作者：
De Bernardis, F;Arancia, S;Cassone, A
通讯作者：
Cassone, A
影响因子：
3.1
作者：
Koshlukova, SE;Araujo, MWB;Edgerton, M
通讯作者：
Edgerton, M
影响因子：
3.8
作者：
Kretschmar, M;Felk, A;Nichterlein, T
通讯作者：
Nichterlein, T
DOI：
10.1073/pnas.141366998
发表时间：
2001-12-04
影响因子：
11.1
作者：
Helmerhorst, EJ;Troxler, RF;Oppenheim, FG
通讯作者：
Oppenheim, FG