Distinct pathways of adaptive evolution in Cryptococcus neoformans reveal a mutation in adenylyl cyclase with trade-offs for pathogenicity.
Distinct pathways of adaptive evolution in Cryptococcus neoformans reveal a mutation in adenylyl cyclase with trade-offs for pathogenicity.
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DOI：
10.1016/j.cub.2023.08.054
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发表时间：
2023-10-09
期刊：
影响因子：
9.2
通讯作者：
Elde, Nels C.
中科院分区：
文献类型：
--
作者：
Hilbert, Zoe A.;Bednarek, Joseph M.;Schwiesow, Mara J. W.;Chung, Krystal Y.;Moreau, Christian T.;Brown, Jessica C. S.;Elde, Nels C.
病原真菌分布在广泛的环境中并感染多种宿主物种。尽管存在巨大的生物学灵活性，但真菌与其宿主之间的相互作用对致病性进化的影响仍不清楚。我们研究了新型隐球菌与相关环境和哺乳动物宿主细胞（阿米巴和小鼠巨噬细胞）之间的重复相互作用如何塑造这种模型真菌病原体的进化。首先，使用一系列新型隐球菌的临床和环境分离株，我们表征了这些菌株在暴露于不同物种的宿主细胞时的一系列生存表型。然后，我们将环境隔离的新型隐球菌菌株通过变形虫或巨噬细胞连续传代约 75 代，以观察这些相互作用如何选择以改善宿主内的复制。在一个适应群体中，我们在腺苷酸环化酶基因 CAC1 中发现了一个单点突变，该突变被固定并赋予巨噬细胞内生长的强大竞争优势。引人注目的是，巨噬细胞的这种生长优势与小鼠感染期间的疾病严重程度呈负相关，这表明对特定宿主生态位的适应可以显着降低这些真菌的致病性。这些结果提出了关于环磷酸腺苷（cAMP）信号对致病性的影响的有趣问题，并强调了看似微小的适应性变化在促进这些重要人类病原体的细胞内行为和毒力的根本转变中的作用。环境微生物（如许多真菌）与不同宿主之间的相互作用可以从根本上改变这些生物体的生物学和致病性。 Hilbert 等人利用自然遗传变异和基于实验室的进化。揭示临床相关真菌病原体适应性进化发生的速度、模式和机制。
Pathogenic fungi populate a wide range of environments and infect a diversity of host species. Despite this substantial biological flexibility, the impact of interactions between fungi and their hosts on the evolution of pathogenicity remains unclear. We studied how repeated interactions between the fungus Cryptococcus neoformans and relevant environmental and mammalian host cells—amoeba and mouse macrophages—shape the evolution of this model fungal pathogen. First, using a collection of clinical and environmental isolates of C. neoformans, we characterized a range of survival phenotypes for these strains when exposed to host cells of different species. We then performed serial passages of an environmentally isolated C. neoformans strain through either amoeba or macrophages for ~75 generations to observe how these interactions select for improved replication within hosts. In one adapted population, we identified a single point mutation in the adenylyl cyclase gene, CAC1, that swept to fixation and confers a strong competitive advantage for growth inside macrophages. Strikingly, this growth advantage in macrophages is inversely correlated with disease severity during mouse infections, suggesting that adaptation to specific host niches can markedly reduce the pathogenicity of these fungi. These results raise intriguing questions about the influence of cyclic AMP (cAMP) signaling on pathogenicity and highlight the role of seemingly small adaptive changes in promoting fundamental shifts in the intracellular behavior and virulence of these important human pathogens. Interactions between environmental microbes, like many fungi, and diverse hosts can fundamentally alter the biology and pathogenicity of these organisms. Using natural genetic variation and laboratory-based evolution, Hilbert et al. reveal the tempo, mode, and mechanisms by which adaptive evolution occurs in a clinically relevant fungal pathogen.
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影响因子：
9.2
作者：
Alvarez, Mauricio;Casadevall, Arturo
通讯作者：
Casadevall, Arturo
影响因子：
30.3
作者：
Denham, Steven T.;Brammer, Brianna;Chung, Krystal Y.;Wambaugh, Morgan A.;Bednarek, Joseph M.;Guo, Li;Moreau, Christian T.;Brown, Jessica C. S.
通讯作者：
Brown, Jessica C. S.
DOI：
10.3390/jof4010039
发表时间：
2018-03-20
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Basenko EY;Pulman JA;Shanmugasundram A;Harb OS;Crouch K;Starns D;Warrenfeltz S;Aurrecoechea C;Stoeckert CJ Jr;Kissinger JC;Roos DS;Hertz-Fowler C
通讯作者：
Hertz-Fowler C
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
15.9
作者：
Al-Quadan, Tasneem;Price, Christopher T.;Abu Kwaik, Yousef
通讯作者：
Abu Kwaik, Yousef