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White Candide is an important human pathogenic fungus.
75 million cases of vaginal infections in women caused by Candida each year, 13 million cases of thrush, and more than 400,000 cases of blood and deep organ infections.
because of the relatively backward research on the basic biology and infection mechanism of Candiosis, there are very limited clinical drugs for the prevention and treatment of Candococ disease.
development is the most important pathogenic characteristic of white candococcus, inhibiting the development of mycelium leads to a sharp decrease in the toxicity of the pathogenic bacteria.
therefore, mycelium development-related factors are also ideal targets for new anti-candococ drugs.
acid cycle (TCA) is the core process of all biomass and energy metabolism, regulating important physiological activities of cells by producing "energy currency" ATP and metabolic intermediates.
as a white canducine species of Crabtree, the TCA cycle is particularly important in environments adapted to low oxygen and high concentrations of carbon dioxide in human hosts.
Recently, Huang Guanghua of the Institute of Microbiology of the Chinese Academy of Sciences systematically analyzed the functions of related genes in white candocyte substances and energy metabolism, carbon dioxide sensing, and disease-causing characteristics regulation, starting with the TCA cycle.
found that a series of key proteins, such as citric acid synthase and shun-head acidase, which regulate the utilization of carbon sources and the development of mycelium, revealed the mechanism of action of related factors through genetic and biochemical means.
, the study found that the TCA cycle, along with the thermal reaction regulator Sfl2 and the conservative cAMP/PKA signaling path, co-regulates changes in carbon dioxide concentrations in the white Candococ induction environment.
energy molecules ATP and second messenger cAMP as small molecules to establish a link between the TCA cycle and the cAMP/PKA signaling path.
TCA cycle activates the cAMP/PKA signaling path by producing ATP and promoting an increase in in-cell cAMP concentration, while the cAMP/PKA signaling path regulates in-cell metabolic patterns through transcription factors Efg1 and Sfl2.
increased concentration of carbon dioxide in the environment promotes the metabolic activity of TCA cycle and the growth of mycelium.
the thermal reaction regulatory factor Sfl2 plays an important regulatory role in this process, and RNA sequencing shows that knocking out the SFL2 gene significantly blocks the response effect of white Candococ to elevated carbon dioxide concentrations.
This study reveals for the first time the role of TCA cycle in the induction of carbon dioxide and the regulation of pathogenic characteristics of white Candiosis, reveals the mechanism of multiple signaling pathogens to respond to changes in the host environment through small molecules, enhances the understanding of the environment adaptation mechanism of pathogenic fungi, and provides new ideas for the development of new anti-Candococ drugs.
research has been published in the international journal PLoS Genetics, associate researcher Tao Li is the first author of the article, researcher Huang Guanghuahua communications author.
the research was funded by the National Natural Science Foundation of China's "Face Project", "Yu qing", "Jie Qing" project and the Chinese Academy of Sciences Youth Innovation Promotion Association.
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