人類血清可以有效地誘導(dǎo)多態(tài)真菌病原體——白色念珠菌的菌絲生長,白色念珠菌會導(dǎo)致嚴(yán)重感染,。真菌腺嘌呤環(huán)化酶Cyr1p是cAMP/PKA信號傳導(dǎo)通路的一個關(guān)鍵組成部分,,該通路控制著不同的相關(guān)感染性狀,包括菌絲的形態(tài)形成,。然而,,目前有關(guān)血清菌絲誘導(dǎo)特點(diǎn)及其真菌傳感器的機(jī)制仍屬未知,。
在7月17日《細(xì)胞—宿主與微生物》(Cell Host & Microbe)發(fā)表的一項(xiàng)最新研究中,Xu等人的分析結(jié)果表明,,活化血清的組分中含有細(xì)菌的類肽聚糖(PGN)分子,。而有幾個純化和合成的胞壁酰二肽(MDPs)與細(xì)菌的類肽聚糖的亞基能夠有效地促進(jìn)白色念珠菌的菌絲生長。
通常情況下,,哺乳動物的傳感器Nod1和Nod2可以通過LRR域識別PGN的類似物,,Xu等人的研究表明,胞壁酰二肽(MDPs)可以通過直接與其LRR域結(jié)合來激活Cyr1p,。如果在宿主和白色念珠菌感染的腸道內(nèi)有豐富的PGN存在,,新的研究結(jié)果對這種病原體的感染機(jī)制具有重大意義。(生物谷Bioon.com)
生物谷推薦原始出處:
Cell Host & Microbe,,Vol 4, 28-39, 17 July 2008,,Xiao-Li Xu, Yong Zhu, and Yue Wang
Bacterial Peptidoglycan Triggers Candida albicans Hyphal Growth by Directly Activating the Adenylyl Cyclase Cyr1p
Xiao-Li Xu,1,2 Raymond Teck Ho Lee,1,2 Hao-Ming Fang,1,2 Yan-Ming Wang,1 Rong Li,1 Hao Zou,1 Yong Zhu,1 and Yue Wang1, Bioon
1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), 61 Biopolis Drive, Proteos, Singapore 138673
Corresponding author
Yue Wang
[email protected]
Summary
Human serum potently induces hyphal development of the polymorphic fungal pathogen Candida albicans, a phenotype that contributes critically to infections. The fungal adenylyl cyclase Cyr1p is a key component of the cAMP/PKA-signaling pathway that controls diverse infection-related traits, including hyphal morphogenesis. However, identity of the serum hyphal inducer(s) and its fungal sensor remain unknown. Our initial analyses of active serum fractions revealed signs of bacterial peptidoglycan (PGN)-like molecules. Here, we show that several purified and synthetic muramyl dipeptides (MDPs), subunits of PGN, can strongly promote C. albicans hyphal growth. Analogous to PGN recognition by the mammalian sensors Nod1 and Nod2 through their leucine-rich-repeat (LRR) domain, we show that MDPs activate Cyr1p by directly binding to its LRR domain. Given the abundance of PGN in the intestine, a natural habitat and invasion site for C. albicans, our findings have important implications for the mechanisms of infection by this pathogen.