REGULATION OF TRICHOPHYTON-RUBRUM PROTEOLYTIC ACTIVITY
REGULATION OF TRICHOPHYTON-RUBRUM PROTEOLYTIC ACTIVITY
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DOI：
10.1128/iai.57.10.3081-3090.1989
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发表时间：
1989-10-01
影响因子：
3.1
通讯作者：
MCKERROW, JH
中科院分区：
文献类型：
--
作者：
APODACA, G;MCKERROW, JH
红色毛癣菌是人类最常见的皮肤真菌，通常定植在表皮的浅层（角质层）。几种蛋白酶与宿主蛋白质的代谢中可能的作用已被纯化，从这种真菌。从生物化学水平研究了这些酶的调控及其在真菌代谢中的作用。一般蛋白水解（azocolytic）活性抑制时，对数期培养的T。在含有容易代谢的碳、氮、硫和磷源的基本培养基中生长红球藻。当碳，氮，或硫从这个基本培养基中删除，azocolytic活性去抑制。在所有情况下，均表现出高分子量活性（Mr> 200，000）。一个71，000-Mr蛋白酶中观察到氮耗尽的文化，和蛋白水解的种类先生124，000和27，000分泌在硫耗尽的文化。添加无机硫（MgSO 4，Na 2SO 3，NaS 2 O3）或有机硫（蛋氨酸，半胱氨酸）的硫耗尽介质抑制的azocolytic活性的表达。相反，角质分解活性不受碳、氮或硫的抑制，而是在基本培养基中加入蛋白质源时诱导。T.红色组成型分泌所有蛋白水解活性。与对数期培养物不同，静止期培养物在基本培养基中分泌偶氮溶解、弹性蛋白溶解和角蛋白溶解活性。这些活动下降，碳，氮，磷耗尽的媒体，但仍然很高，在硫耗尽的介质。提出了以下模型用于调节T。红蛋白水解活性。在感染的最初阶段，T.红葡萄生长缓慢。在这种状态下，当真菌环境中缺乏碳、氮或硫时，蛋白水解活性被去抑制。所产生的一般蛋白酶作用于角质层中的非角质蛋白。可能有一些尚未鉴定的肽酶，能将最初的蛋白水解产生的肽裂解成氨基酸。这些氨基酸将为细胞提供碳、氮和硫的来源。在这些条件下，一般蛋白酶的表达将被抑制，而特定的角蛋白酶将在这种营养丰富的环境中被诱导。当真菌达到稳定期时，当蛋白酶组成性分泌时，可能发生疾病。这些酶可能直接或间接地激发宿主反应，导致皮肤真菌病的炎症表现。
Trichophyton rubrum is the most common dermatophyte of humans and normally colonizes the superficial layers of the epidermis (stratum corneum). Several proteinases with a possible role in the metabolism of host proteins have been purified from this fungus. The regulation of these enzymes and their role in fungal metabolism were studied at the biochemical level. General proteolytic (azocollytic) activity was repressed when log-phase cultures of T. rubrum were grown in a minimal medium that contained readily metabolized sources of carbon, nitrogen, sulfur, and phosphorus. When either carbon, nitrogen, or sulfur was deleted from this minimal medium, azocollytic activity was derepressed. In all cases a high-molecular-weight activity (Mr, > 200,000) was expressed. A 71,000-Mr proteinase was observed in nitrogen-depleted cultures, and proteolytic species of Mr 124,000 and 27,000 were secreted in sulfur-depleted cultures. The addition of either inorganic (MgSO4, Na2SO3, NaS2O3) or organic (methionine, cysteine) sulfur to the sulfur-depleted medium repressed the expression of azocollytic activity. In contrast, keratinolytic activity was not repressed by carbon, nitrogen, or sulfur but instead was induced when a protein source was included in the minimal medium. Stationary-phase cultures of T. rubrum secreted all proteolytic activities constitutively. Unlike log-phase cultures, the stationary-phase cultures secreted azocollytic, elastinolytic, and keratinolytic activity in minimal medium. These activities fell in the carbon-, nitrogen-, and phosphorous-depleted media but remained high in sulfur-depleted medium. The following model is proposed for the regulation of T. rubrum proteolytic activity. In the initial stages of infection, T. rubrum grows logarithmically. In this state, proteolytic activity is derepressed whenever carbon, nitrogen, or sulfur is lacking in the fungal milieu. The general proteinases produced would act on the nonkeratinous proteins in the stratum corneum. There are probably peptidases, as yet unidentified, that would cleave the peptides generated by the initial proteolysis into amino acids. These amino acids would provide the cell with a source of carbon, nitrogen, and sulfur. Under these conditions, the expression of general proteinases would be repressed, whereas specific keratinases would be induced in this nutrient-rich environment. Disease may occur when the fungus reaches stationary phase, when proteinases are secreted constitutively. These enzymes may directly or indirectly incite a host response, resulting in the inflammatory manifestations of dermatophytosis.