Morphological transformation plays an important role in the rapid adaptation of pathogenic fungi to the host's changing microenvironment. Candida albicans (Candida albicans) is an important opportunistic fungus in the human body, usually symbiotic in healthy people does not cause any adverse reactions, but in immunocompromised people may cause organ mucosal infection and life-threatening blood infection. In recent years, due to the widespread use of broad-spectrum antibiotics, the application of new medical technologies such as cancer chemotherapy and organ transplantation, the prevalence of AIDS and the aging of the population, fungal infections mainly caused by Candida albicans have become an increasingly serious clinical problem .
Candida albicans is both a symbiotic human body and a two-sided pathogen. It is determined by its unique biological characteristics and is the result of a long-term co-evolution of interaction with the host. The pathogenicity of Candida albicans is closely related to its morphogenesis and sexual reproduction. In the 1980s, the Soll laboratory in the United States discovered for the first time that Candida albicans could undergo a reversible and heritable morphological transformation, namely "white fungus-gray fungus morphological transformation". White fungus and gray fungus cells differ in many aspects such as morphology, toxicity, sensitivity to host immune cells and mating ability. For a long time, it has been considered that only a small number of strains (less than 8%) can undergo white-gray fungus morphological transformation in clinic. These strains are homozygous (MTL, a / a or α / α). While the clinically dominant MTL heterozygous (a / α) strain, although its genome contains all the genes necessary for morphological transformation, the conversion of white bacteria to gray fungus has never been found before.
Recently, the research team of Huang Guanghua and Bai Fengyan of the Institute of Microbiology of the Chinese Academy of Sciences found that under simulated host environment conditions, Candida albicans MTL heterozygous strains and homozygous strains can also undergo white fungus-gray fungus morphological transformation. The gray bacteria colonies and cell morphology of MTL heterozygous strains are similar to those of homozygous strains, and the toxicity of gray bacteria and white bacteria in different mouse infection models is significantly different. Further studies have found that transcription factors Rfg1, Brg1 and Efg1 are used as negative regulatory factors, and Wor1, Wor2 and Czf1 are used as positive regulatory factors, synergistically regulating the expression of WOR1, a key gene for morphological transformation of white fungus and gray fungus, thereby determining MTL hybrid strains The form is built. This study reveals the general characteristics of Candida albicans morphological transformation of white fungus and gray fungus, improves the understanding of the microenvironment adaptation, pathogenicity and sexual reproduction of the host, and modifies the regulation of morphological transformation of white fungus and gray fungus Theory, and provide new ideas for the prevention and treatment of candidiasis, has important clinical significance.
The research was completed under the support of the "Hundred Talents Program" and related projects of the National Natural Science Foundation of China and was supported by Zhang Lixin's research group at the Institute of Microbiology and the Sandy Johnson Laboratory at the University of California, San Francisco. Related research results were recently published in the international journal PLoS Biology.
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