The Candida glabrata Parent Strain Trap: How Phenotypic Diversity Affects Metabolic Fitness and Host Interactions.
The Candida glabrata Parent Strain Trap: How Phenotypic Diversity Affects Metabolic Fitness and Host Interactions.
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DOI：
10.1128/spectrum.03724-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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参考菌株通过标准化观察和方法提高再现性，这最终导致了对真菌发病机制的重要见解。然而，最近的研究强调了不同分离株之间显著的基因型和表型异质性，这些异质性会影响一个物种内的遗传回路和毒力。光秃念珠菌是念珠菌病的第二大病因，念珠菌病是一种危及生命的感染，在应激反应中发生广泛的核型和表型变化。对这种病原体进行的大部分工作集中在两个测序菌株CBS138 （ATCC 2001）和BG2上。很少有研究详细比较这些菌株，但关键的差异包括交配类型和EPA粘附素表达模式的改变。事实上，大多数glabrata分离株和BG2是MATa，而CBS138是MATa α。然而，目前尚不清楚这些菌株之间的其他表型差异是否在我们对光棘球霉发病机制的理解中起作用。因此，我们开始表征CBS138和BG2的代谢、细胞壁和宿主相互作用属性。我们发现BG2比CBS138利用更广泛的氮源，细胞壁大小和碳水化合物暴露减少，我们假设这导致先天免疫相互作用和毒力的差异。我们观察到，尽管这两种菌株被吞噬的程度相似，但BG2在巨噬细胞中复制的数量更高，并且在感染mellonella时比CBS138更具毒力，且呈剂量依赖性。有趣的是，与亲本菌株相比，缺失SNF3（主要的营养传感器）并不会影响BG2对mellonella的毒力，但在CBS138背景下，与亲本菌株相比，SNF3显著增强了幼虫的杀伤能力。了解这些代谢和宿主相互作用的基本差异将有助于在未来的研究中得出更有力的结论。重要性：参考菌株对真菌病原体的毒力机制提供了重要的见解。然而，最近对白色念珠菌和其他物种的研究揭示了临床分离株中显着的基因型和表型多样性，这对关键毒力因子及其调控的范式提出了挑战。光滑念珠菌是念珠菌病的第二大病因，许多研究使用BG2或CBS138进行调查。因此，我们的目的是表征这两种菌株的重要毒力相关表型，这可能会改变关于光棘球蚴发病机制的结论。我们的研究提供了代谢和细胞壁变化的背景，以及这些变化如何影响宿主相互作用表型。了解这些差异对于支持关于毒力因子如何在这些和其他非常不同的菌株背景下发挥作用的有力结论是必要的。
Reference strains improve reproducibility by standardizing observations and methodology, which has ultimately led to important insights into fungal pathogenesis. However, recent investigations have highlighted significant genotypic and phenotypic heterogeneity across isolates that influence genetic circuitry and virulence within a species. Candida glabrata is the second leading cause of candidiasis, a life-threatening infection, and undergoes extensive karyotype and phenotypic changes in response to stress. Much of the work conducted on this pathogen has focused on two sequenced strains, CBS138 (ATCC 2001) and BG2. Few studies have compared these strains in detail, but key differences include mating type and altered patterns of expression of EPA adhesins. In fact, most C. glabrata isolates and BG2 are MATa, while CBS138 is MATα. However, it is not known if other phenotypic differences between these strains play a role in our understanding of C. glabrata pathogenesis. Thus, we set out to characterize metabolic, cell wall, and host-interaction attributes for CBS138 and BG2. We found that BG2 utilized a broader range of nitrogen sources and had reduced cell wall size and carbohydrate exposure than CBS138, which we hypothesized results in differences in innate immune interactions and virulence. We observed that, although both strains were phagocytosed to a similar extent, BG2 replicated to higher numbers in macrophages and was more virulent during Galleria mellonella infection than CBS138 in a dose-dependent manner. Interestingly, deletion of SNF3, a major nutrient sensor, did not affect virulence in G. mellonella for BG2, but significantly enhanced larval killing in the CBS138 background compared to the parent strain. Understanding these fundamental differences in metabolism and host interactions will allow more robust conclusions to be drawn in future studies of C. glabrata pathogenesis. IMPORTANCE Reference strains provide essential insights into the mechanisms underlying virulence in fungal pathogens. However, recent studies in Candida albicans and other species have revealed significant genotypic and phenotypic diversity within clinical isolates that are challenging paradigms regarding key virulence factors and their regulation. Candida glabrata is the second leading cause of candidiasis, and many studies use BG2 or CBS138 for their investigations. Therefore, we aimed to characterize important virulence-related phenotypes for both strains that might alter conclusions about C. glabrata pathogenesis. Our study provides context for metabolic and cell wall changes and how these may influence host interaction phenotypes. Understanding these differences is necessary to support robust conclusions about how virulence factors may function in these and other very different strain backgrounds.
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影响因子：
28.3
作者：
Ballou ER;Avelar GM;Childers DS;Mackie J;Bain JM;Wagener J;Kastora SL;Panea MD;Hardison SE;Walker LA;Erwig LP;Munro CA;Gow NA;Brown GD;MacCallum DM;Brown AJ
通讯作者：
Brown AJ
影响因子：
3.1
作者：
Brieland, J;Essig, D;Hare, R
通讯作者：
Hare, R
DOI：
10.3390/jof6030121
发表时间：
2020-07-30
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
O'Kane CJ;Weild R;M Hyland E
通讯作者：
M Hyland E
影响因子：
64.8
作者：
Dujon, B;Sherman, D;Souciet, JL
通讯作者：
Souciet, JL
DOI：
10.1073/pnas.0611195104
发表时间：
2007-05-01
影响因子：
11.1
作者：
Kaur, Rupinder;Ma, Biao;Cormack, Brendan P.
通讯作者：
Cormack, Brendan P.