在Cryptococcus neoformans中,不同的适应性进化途径揭示了腺环酶的突变,与致病性进行了权衡
Zoë A Hilbert1, Joseph M Bednarek2, Mara J W Schwiesow1
1Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Current biology : CB
|September 14, 2023
概括
与阿米巴和巨菌的相互作用可以改变真菌病原体Cryptococcus neoformans evolution. 适应宿主细胞可能会降低病原性,影响循环AMP (cAMP) 信号和毒性.
科学领域:
- 微生物学 微生物学
- 进化生物学 进化生物学
- 病变发生学研究 病变发生学研究
背景情况:
- 病原菌表现出显著的环境和宿主适应性.
- 宿主真菌相互作用对真菌病原性的进化影响尚不清楚.
- 新型菌 (Cryptococcus neoformans) 作为研究真菌病原体演变的模型生物.
研究的目的:
- 为了研究与环境 (阿米巴) 和哺乳动物 (巨) 主体细胞的重复相互作用如何塑造Cryptococcus neoformans致病性的进化.
- 为了确定由宿主特异性选择压力导致的C. neoformans的遗传和表型变化.
- 探索宿主适应和C. neoformans的毒性之间的关系.
主要方法:
- 对临床和环境C. neoformans对不同宿主细胞分离的生存表型的表征.
- 环境中C. neoformans菌株的连续通道实验通过约75代的阿米巴和巨细胞.
- 基因分析以确定突变,包括全基因组测序,以及功能分析以评估它们对生长和毒性的影响.
主要成果:
- 重复的宿主细胞相互作用被选择用于改善宿主体内的C. neoformans复制.
- 腺环酶基因CAC1的一个单点突变赋予了巨细胞的竞争性增长优势.
- 对巨细胞的这种适应在小鼠感染模型中显示出与疾病严重程度的逆相关性.
- 循环AMP (cAMP) 信号与观察到的致病性变化有关.
结论:
- 适应特定的宿主,如巨细胞,可以显著改变真菌的致病性.
- 由宿主相互作用驱动的进化变化可能导致病毒毒性降低,挑战了对病原体适应的传统观点.
- 这项研究强调了cAMP信号在调节细胞内行为和C. neoformans等真菌病原体的毒性方面发挥的关键作用.
相关概念视频
Transduction
38
Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
38
Cystic Fibrosis: Pathogenesis
275
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
275
cAMP-dependent Protein Kinase Pathways
6.4K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
GPCRs Regulate Adenylyl Cylase Activity
5.7K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Intracellular Signaling Cascades
47.0K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
47.0K


