UGA35, A New Factor That Regulates The Alkalinization Of The External Environment PH By Candida Albicans

In recent years,due to the increasing number of AIDSpatients and immunosuppressive therapy widely used in clinical,immunocompromised population increased year by year.In immunocompromised patients,Candida albicans may disseminate into bloodstream,causing life-threaterning systemic candidiasis.The associated mortality rates of systemic infection are reported to be greater than 30%,highlighting the potential critical impact of C.albicans.Candidiasis is a fungal disease,caused by candida genus,especially by Candida albicans,frequently leading immuno-compromised patient to superficial mucosal and skin infection,as well as the severe disease of deep systematic infection.C.albicans can survive as multiple forms existing in the organism,containing yeast,hypha and pseudohypha.They have the ability to switch among each other and the ability of switching reversibly between budding yeast and hypha is highly associated with virulence.The factors that affect the transformation of Candida albicans include carbon dioxide,serum,37 DEG C and medium.In this study,we screened the C.albicans gene knockout Library in laboratory,we found that when C.albicans deletion of transcription factor UGA35,there are se alkaline pH rious defects in the alkaline environment pH.At the same time,we also found that the uga35A strain could not absorb the amino acids in the external environment,which resulted in severe growth defects.Previous reports have shown that the transcription factor STP2 plays a very important role in the process of pH.In order to further study the role of UGA35 in pH,we further studied the relationship between UGA35 and STP2.The study found UGA35 promoted Stp2 protein N end cutting.By infecting macrophages,the ability of macrophages to escape UGA35 was decreased,and the survival rate of C.albicans was decreased in uga35A.Furthermore,it was found that the virulence of the mice infected by systemic infection was decreased,and the survival rate of mice was greatly improvedIn recently years,with plenty use of antibiotics,hormone,immunosuppressive agents,the morbidity and mortality of fungal infection present rising trend,especially in C.albicans infections,which highlights the fact that C.albicans must have formed a unique set of strategies to enhance drug tolerance and reduce antifungal susceptibility.So it is meaningful for us to find drug target genes and design novel drugs that are vital for prevent against fungal infection.The research has laid a solid foundation of potential therapeutic targets for treating infections theoretically.We hope to design a novel drug to inhibit Uga35 protein’s functions and expressions,preventalkaline the enviernment pH,and reduce virulence and inhibit C.albicans infections eventually.