The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice.
The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice.
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DOI：
10.1371/journal.ppat.1006699
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发表时间：
2017-10
期刊：
影响因子：
6.7
通讯作者：
Pérez JC
中科院分区：
文献类型：
--
作者：
Böhm L;Torsin S;Tint SH;Eckstein MT;Ludwig T;Pérez JC
许多引起人体全身性、危及生命的感染的微生物作为无害的寄生虫存在于我们的消化道中。然而，人们对肠道中这些微生物的生物学知之甚少。在这里，我们可视化的界面之间的人类肠道和致病真菌白色念珠菌和肠道的小鼠，一个替代主机。因为本土小鼠微生物群限制了C。白念珠菌定居，我们比较了无菌和驱虫处理的常规饲养小鼠肠道中的定植模式。与后者中发现的异质形态相反，我们确定，在无菌动物中，真菌几乎一致地采用酵母细胞形式，这是其寄生状态的代表。通过筛选C.白念珠菌转录调节因子缺失突变体在gnotobiotic小鼠，我们确定了几个基因以前未知的，有助于在体内健身。我们研究了其中的三种调节剂-ZCF 8，ZFU 2和TRY 4-并表明它们确实有利于酵母形式而不是其他形态。与这一发现一致，我们证明遗传诱导非酵母细胞形态对C的适应性有害。肠道内有白色念珠菌此外，所鉴定的调节剂促进真菌粘附于覆盖有粘蛋白的表面和产生粘蛋白的肠上皮细胞。与此结果一致，组织学切片表明C。白色念珠菌居住在小鼠肠道中，紧邻粘液层。因此，我们的研究结果揭示了一组赋予C。白色念珠菌具有通过多种机制在肠内耐受的能力。导致危及生命的人类疾病的微生物通常是我们粘膜表面的无害居民。然而，这个所谓的“奴隶制”国家的特征仍然没有得到充分的探索。在这份报告中，我们调查的情况下，白色念珠菌，最突出的真菌物种生活在人类肠道，但也是一个常见的原因深层次的，致命的感染。携带自身天然完整植物群的小鼠不易被C.这意味着本土小鼠微生物群和这种真菌之间的根本不相容。我们探讨了C.完全没有其他微生物的小鼠体内的白色念珠菌。我们表明，真菌采用其正常的寄生形态，在这些动物表明，该实验系统是一个合适的代理，清楚地解剖其寄生生活方式在体内。深入了解维持C.白色念珠菌和其他微生物是了解并能够预防的关键，当这些微生物侵入其他组织并引起疾病时，会发生什么错误。
Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms. The very same microbes that cause life-threatening human diseases are often harmless inhabitants on our mucosal surfaces. Yet the hallmarks of this so-called ‘commensal’ state remain underexplored. In this report we investigate the case of Candida albicans, the most prominent fungal species living in the human intestine but also a common cause of deep-seated, fatal infections. Mice carrying their own natural intact flora are not readily colonized by C. albicans implying a fundamental incompatibility between the indigenous mouse microbiota and this fungus. We explore the patterns of colonization of C. albicans in mice completely devoid of other microbes. We show that the fungus adopts its normal commensal morphology in these animals indicating that this experimental system is a suitable proxy to clearly dissect its commensal lifestyle in vivo. Gaining insights into the mechanisms that sustain the commensal features of C. albicans and other microbes is key to understand—and be able to prevent—what goes awry when these microorganisms invade other tissues and cause disease.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.3
作者：
Chen C;Pande K;French SD;Tuch BB;Noble SM
通讯作者：
Noble SM
影响因子：
30.3
作者：
Johansson ME;Jakobsson HE;Holmén-Larsson J;Schütte A;Ermund A;Rodríguez-Piñeiro AM;Arike L;Wising C;Svensson F;Bäckhed F;Hansson GC
通讯作者：
Hansson GC
DOI：
10.1007/978-1-61779-513-8_13
发表时间：
2012-01-01
期刊：
MUCINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Johansson, Malin E. V.;Hansson, Gunnar C.
通讯作者：
Hansson, Gunnar C.
影响因子：
5.4
作者：
Desai, Jigar V.;Mitchell, Aaron P.;Andes, David R.
通讯作者：
Andes, David R.