Salivary histatin 5 internalization by translocation, but not endocytosis, is required for fungicidal activity in Candida albicans.
Salivary histatin 5 internalization by translocation, but not endocytosis, is required for fungicidal activity in Candida albicans.
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DOI：
10.1111/j.1365-2958.2010.07210.x
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发表时间：
2010-07
影响因子：
3.6
通讯作者：
Edgerton M
中科院分区：
文献类型：
--
作者：
Jang WS;Bajwa JS;Sun JN;Edgerton M
唾液组蛋白5(HST-5)是一种阳离子唾液蛋白，对白色念珠菌具有很强的杀菌活性。杀伤需要与细胞壁结合，然后在细胞内转位；然而，特定的结合成分和关键的毒性事件尚不清楚。在本研究中，海带多糖(β-1，3-葡聚糖)而不是唾液酸、甘露聚糖或葡聚糖介导HST5与白色念珠菌的结合，并被100mMNaC l解离。时间推移共聚焦显微镜显示，细胞质摄取HST5的速率与剂量相关，总是先于碘化丙啶(PI)进入，这表明易位本身并不破坏膜的完整性。细胞毒性表现为空泡扩张后PI进入；然而，HST5内吞空泡运输的丧失并不减少杀伤力。胞外氯化钠(100 MM)，但山梨醇不能阻止已经含有胞浆HST5的细胞的空泡扩张和PI进入，因此在HST5毒性中显示了离子平衡的关键作用。叠氮或间氯苯肼可阻断HST-5摄取，但不能阻止细胞壁结合；然而，10%的失能细胞有膜破裂。因此，HST5具有异质性的细胞内进入途径，但只有胞浆直接易位才会导致离子外流导致细胞死亡。
Salivary histatin 5 (Hst 5) is a cationic salivary protein with high fungicidal activity against Candida albicans. Binding to the cell wall followed by intracellular translocation is required for killing; however, specific binding components and critical toxic events are not understood. In this study, laminarin (β-1,3-glucan) but not sialic acid, mannan or pustulan mediated Hst 5 binding to C. albicans, and was disassociated by 100 mM NaCl. Time-lapse confocal microscopy revealed a dose-dependent rate of cytosolic uptake of Hst 5 that invariably preceded propidium iodide (PI) entry, demonstrating that translocation itself does not disrupt membrane integrity. Cell toxicity was manifest by vacuolar expansion followed by PI entrance; however, loss of endocytotic vacuolar trafficking of Hst 5 did not reduce killing. Extracellular NaCl (100 mM), but not sorbitol, prevented vacuolar expansion and PI entry in cells already containing cytosolic Hst 5, thus showing a critical role for ionic balance in Hst 5 toxicity. Hst 5 uptake, but not cell wall binding, was blocked by pretreatment with azide or carbonyl cyanide m-chlorophenylhydrazone; however, 10% of de-energized cells had membrane disruption. Thus, Hst 5 is capable of heterogeneous intracellular entry routes, but only direct cytosolic translocation causes cell death as a result of ionic efflux.
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DOI：
10.1016/j.bbamcr.2008.08.003
发表时间：
2009-04
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Li SC;Kane PM
通讯作者：
Kane PM
DOI：
10.1086/523110
发表时间：
2007-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Gow NA;Netea MG;Munro CA;Ferwerda G;Bates S;Mora-Montes HM;Walker L;Jansen T;Jacobs L;Tsoni V;Brown GD;Odds FC;Van der Meer JW;Brown AJ;Kullberg BJ
通讯作者：
Kullberg BJ
影响因子：
4.8
作者：
Aouida, M;Leduc, A;Ramotar, D
通讯作者：
Ramotar, D
影响因子：
4.1
作者：
den Hertog, AL;Sang, HWWF;Amerongen, AVN
通讯作者：
Amerongen, AVN
影响因子：
3.1
作者：
Koshlukova, SE;Araujo, MWB;Edgerton, M
通讯作者：
Edgerton, M