How the human pathogen fungus White Candide regulates the new mechanism of symbia in the host intestine through mitochondrial complex I.

On June 1st, the international academic journal PLOS Pathogens published online the latest research by Chen Changbin of the Pasteur Institute in Shanghai, Chinese Academy of Sciences.
This study describes how the human pathogen fungus White Candina regulates the metabolism of non-fermented carbon sources through mitochondrial complex I to promote mycelium growth, biofilm formation, and new mechanisms of symbia in the host intestine.
In recent years, with the widespread use of immunosuppressants, broad-spectrum antibiotics and corticosteroid hormones, the widespread clinical development of technologies such as catheters, intrinsic tubes and organ transplantation, and the growing prevalence of various diseases, including AIDS, malignant blood diseases, diabetes and autoimmune diseases, the incidence of pathogenic fungal infections has increased dramatically, with candida albicans infections dominating.
This common human-conditional pathogenic fungus is commonly present in healthy populations as symbic bacteria on the surface of the body's mucous membranes (e.g. pharynx, gastrointestinal tract and genitourinary tract) and is not pathogenic, but white candococsis occurs when the body's immune system is inhibited by damage or normal microbiomes interact with each other Can be transformed from symbic bacteria into pathogenic bacteria, infecting almost all organs of the human body leading to serious candococcal disease, including shallow infection (mucosal candococcal disease such as thrush, keratitis, vaginitis, etc.) and deep infection (internal and central neurological candococcal disease such as sepsis).
because of the complexity of white Candide adhesion infection, multiple antifungal drug resistance and the side effects of antifungal drugs, the treatment of this fungal infection has become a clinical difficulty.
In China, white candococ infection accounts for 81.59 percent of all fungal infections, and despite the treatment of antifungal drugs, the death rate of Candococemia is still as high as 40%-80%, of which the death rate of deep white Candococ infection is 68.9%.
because of this high fatality rate, it is an increasingly urgent task to develop new ways to prevent and treat white Candide infection.
studying the molecular mechanism of white candella symbiotic implantation in different habitats of the host (niches) is of great significance for understanding the pathological development process of the bacteria from non-pathogenic symbiotic bacteria to pathogenic bacteria.
Unlike fermented carbon sources such as glucose, which are commonly used in laboratory cultures, the human gut is an extremely poor environment for glucose, and the carbon sources available to microorganisms in the gut are mainly non-fermented carbon sources, such as amino acids, lactic acids, glyceric acid, N-acetyl glucosamine and glycol.
therefore, the effective absorption and utilization of non-fermented carbon sources is very important for white candococ to plant and symbia in the host intestine, but the relevant molecular regulatory mechanism has not been clear.
Huang Xinhua, research assistant of Chen Changbin Research Group at Pasteur Institute in Shanghai, Chen Xiaoqing and He Yongming, master's students, discovered for the first time the important role of mitochondrial complex I in regulating the perception of white Candide and the use of non-fermented carbon source glycol.
the results of the study found that the absence of nuo2, which encodes the ubiquinone redoxase in compound I, led to a decrease in the level of NAD-plus produced by the enzyme catalytic, resulting in the effect of THE-plus-dependent glycol dehydrogenase activity on inhibiting the conversion of glycol to glycol.
the closed sugar enzyme pathway mediated by glucosaccharides causes the electron transfer of the respiratory chain to be blocked, producing a large amount of reactive oxygen (Reactive Oxygen Species; ROS).
the production of ROS causes the activation of glycol-specific signaling pathways, including phosphorylation induction of Hog1 MAPK and reduced transcription factor Brg1 expression.
the expression of Brg1 inhibits transcriptional expression of mycelium-specific genes such as HWP1 and ALS3, which in turn seriously affects the growth of white Candococ filament and biofilm formation.
Further experiments on infection in mice found that the lack of function of mitochondrial complex I led to defects in the intestinal symbonic capacity of white Candide bacteria, while artificial supplementation of fermented carbon source glucose can significantly improve the intestinal implantation of compound I mutant strains, fully demonstrating that the ability of white candococ to utilize non-fermented carbon sources is essential for its symbational planting in the host intestinal environment, and mitochondrial complex I plays a key regulatory role.
Mitochondrial complex I through the regulation of non-fermented carbon sources to promote the growth of white Candococ filament, biofilm formation and host intestinal symbia molecular mechanism pattern map research work has been the Chinese Academy of Sciences Institute of Zoology researcher Zhan Xiangjiang, The Institute of Microbiology Epidemiology of the Academy of Military Medical Sciences researcher Zhou Dongsheng, Tongji University Medical College affiliated Oriental Hospital Inspection Department Professor Wu Wenxuan, Second Military Medical University affiliated Changhai Hospital dermatology professor Wu Jianhua strong support and collaboration.
the study was supported by the National Natural Science Foundation of China, the Chinese Academy of Sciences' 100-person program, the Ministry of Science and Technology project and the Shanghai Natural Science Foundation.
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