A p21-activated kinase is required for conidial germination in Penicillium marneffei.
A p21-activated kinase is required for conidial germination in Penicillium marneffei.
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DOI：
10.1371/journal.ppat.0030162
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发表时间：
2007-11
期刊：
影响因子：
6.7
通讯作者：
Andrianopoulos A
中科院分区：
文献类型：
--
作者：
Boyce KJ;Andrianopoulos A
无性孢子（分生孢子）是许多病原真菌的感染性繁殖体，感知寄主环境和触发分生孢子萌发的能力是关键的致病性决定因素。分生孢子的萌发需要重新建立一个极化的生长轴和随后的胚管延伸。在萌发过程中控制极化的分子机制尚不清楚。在二态人类致病真菌马尔尼菲青霉中，分生孢子萌发产生两种细胞类型中的一种，这两种细胞类型对环境线索的反应有着截然不同的命运。在25°C时，分生孢子萌发产生腐生细胞类型，分离的多核菌丝，具有无性发育的能力。在37°C时，分生孢子萌发产生致病细胞类型，关节分生菌丝释放单核酵母细胞。本研究表明，p21激活的激酶pakA是酵母细胞在37°C条件下分生孢子萌发和极化生长过程中极性建立机制的重要组成部分，但在25°C条件下萌发或极化生长并不需要。分析表明，异三聚体G蛋白α亚基GasC和CDC42同源基因CflA均位于PakA的上游，而Ras同源基因RasA仅在25℃时起作用。这些发现表明，尽管一些调节出芽酵母极化生长的蛋白质在丝状真菌中是保守的，但电路和下游效应物受到不同的调节，从而产生不同的细胞类型。许多真菌感染是由休眠的真菌孢子进入宿主而引起的。一旦进入宿主，这些休眠的孢子必须重新激活（发芽）才能继续感染。生产性感染需要真菌在宿主内生长和分裂，这使得了解控制萌发的机制对于开发真菌感染的预防性或预防性治疗至关重要。控制孢子萌发的分子机制尚不清楚，对机会真菌病原体马尔尼菲青霉的研究表明，一组高度保守的信号传导和细胞极性因子，即小GTPases，在孢子萌发和形态发生的其他方面起着重要作用。在这项研究中，我们已经证明了这些小gtpase的下游靶点，p21激活的激酶在37°C而不是25°C的寄主温度下的萌发中起关键作用。这是萌发的第一个组成部分，它显示了温度依赖效应，并提供了真菌病原体感染宿主或在非宿主环境中腐生生长的不同机制的见解。
Asexual spores (conidia) are the infectious propagules of many pathogenic fungi, and the capacity to sense the host environment and trigger conidial germination is a key pathogenicity determinant. Germination of conidia requires the de novo establishment of a polarised growth axis and consequent germ tube extension. The molecular mechanisms that control polarisation during germination are poorly understood. In the dimorphic human pathogenic fungus Penicillium marneffei, conidia germinate to produce one of two cell types that have very different fates in response to an environmental cue. At 25 °C, conidia germinate to produce the saprophytic cell type, septate, multinucleate hyphae that have the capacity to undergo asexual development. At 37 °C, conidia germinate to produce the pathogenic cell type, arthroconidiating hyphae that liberate uninucleate yeast cells. This study shows that the p21-activated kinase pakA is an essential component of the polarity establishment machinery during conidial germination and polarised growth of yeast cells at 37 °C but is not required for germination or polarised growth at 25 °C. Analysis shows that the heterotrimeric G protein α subunit GasC and the CDC42 orthologue CflA lie upstream of PakA for germination at both temperatures, while the Ras orthologue RasA only functions at 25 °C. These findings suggest that although some proteins that regulate the establishment of polarised growth in budding yeast are conserved in filamentous fungi, the circuitry and downstream effectors are differentially regulated to give rise to distinct cell types. Many fungal infections are initiated by the entry of dormant fungal spores into their host. Once inside the host these dormant spores must reactivate (germinate) for the infection to proceed. Productive infections necessitate that the fungus grow and divide within the host, which makes understanding the mechanisms that control germination crucial to developing preventative or prophylactic treatments for fungal infections. The molecular mechanisms that control spore germination are poorly understood and studies of the opportunistic fungal pathogen Penicillium marneffei have shown that a group of highly conserved signalling and cell polarity factors, known as small GTPases, play important roles in germination and other aspects of morphogenesis. In this study we have shown that a downstream target of these small GTPases, a p21-activated kinase plays a crucial role in germination at the host temperature of 37 °C but not at 25 °C. This is the first component of germination, which shows temperature-dependent effects and provides insights into the different mechanisms used by fungal pathogens to infect their host or to grow saprophytically in non-host environments.
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