Swidergall Marc, Ernst Joachim F
Department Biologie, Molekulare Mykologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
Department Biologie, Molekulare Mykologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Eukaryot Cell. 2014 Aug;13(8):950-7. doi: 10.1128/EC.00093-14. Epub 2014 Jun 20.
Antimicrobial peptides (AMPs) are key elements of innate immunity, which can directly kill multiple bacterial, viral, and fungal pathogens. The medically important fungus Candida albicans colonizes different host niches as part of the normal human microbiota. Proliferation of C. albicans is regulated through a complex balance of host immune defense mechanisms and fungal responses. Expression of AMPs against pathogenic fungi is differentially regulated and initiated by interactions of a variety of fungal pathogen-associated molecular patterns (PAMPs) with pattern recognition receptors (PRRs) on human cells. Inflammatory signaling and other environmental stimuli are also essential to control fungal proliferation and to prevent parasitism. To persist in the host, C. albicans has developed a three-phase AMP evasion strategy, including secretion of peptide effectors, AMP efflux pumps, and regulation of signaling pathways. These mechanisms prevent C. albicans from the antifungal activity of the major AMP classes, including cathelicidins, histatins, and defensins leading to a basal resistance. This minireview summarizes human AMP attack and C. albicans resistance mechanisms and current developments in the use of AMPs as antifungal agents.
抗菌肽(AMPs)是固有免疫的关键要素,能够直接杀灭多种细菌、病毒和真菌病原体。具有医学重要性的白色念珠菌作为正常人类微生物群的一部分,定殖于不同的宿主生态位。白色念珠菌的增殖通过宿主免疫防御机制和真菌反应的复杂平衡来调节。针对致病真菌的抗菌肽表达受到差异调节,并由多种真菌病原体相关分子模式(PAMPs)与人细胞上的模式识别受体(PRRs)相互作用引发。炎症信号传导和其他环境刺激对于控制真菌增殖和防止寄生也至关重要。为了在宿主体内持续存在,白色念珠菌已开发出一种三相抗菌肽逃避策略,包括分泌肽效应物、抗菌肽外排泵以及调节信号通路。这些机制使白色念珠菌对包括cathelicidins、组蛋白和防御素在内的主要抗菌肽类别的抗真菌活性产生抗性,从而导致基础抗性。本综述总结了人类抗菌肽的攻击和白色念珠菌的抗性机制,以及将抗菌肽用作抗真菌剂的当前进展。