The Study Of Drug-Resistant Related Metabolites Of Candida Albicans By Comparative Metabolomics

Candida albicans is the most common fungal pathogen associated with Systemicfungal infections. C. albicans have emerged as a growing threat to human health,especially for an increasing number of immunocompromised patients who are at risk foropportunistic infections. In addition, candidiasis is frequently associated with biofilmformation on both inert and biological surfaces, and cells within these biofilms areintrinsically resistant to most antifungal agents and host defenses.The most effective classes of antifungal agents used to treat Candida infections are theazoles, polyenes, and echinocandins. These classes of antifungal agents represent a limitedarsenal of drugs used to combat Candida infections; moreover, these agents also havesignificant limitations that restrict their routine clinical use. The azole antifungals arefungistatic, are associated with drug-drug interactions, and are hindered by the emergenceof azole-resistant species of C. albicans. The polyene agents have adverse side effects,such as nephrotoxicity, renal failure, and infusion-related toxicity. The echinocandinantifungals are somewhat costly and have been associated with fever, thrombophlebitis,and hepatic toxicity. In the face of these limitations, the identification of novel antifungaltargets and the development of new antifungal agents are warranted for the effectivetreatment of Candida infections.Shikonin, a naphthoquinone isolated from the Chinese herbal plant Lithospermumerythrorhizon, has been broadly used for thousands of years in traditional Chinesemedicine for the treatment of burns, carbuncles, measles, macular eruptions, and sorethroats. Recent studies have demonstrated that shikonin has significant antitumor,antioxidants and anti-inflammatory drug potential. It has been shown that shikonin has theability to induce apoptosis, cell death and inhibit the cell growth. Our study also showed itcan be used as potential antifungal drug which have in vitro antifungal activity against C.albicans.Nowadays genomics and proteomics have done a lot of significant research, but toclarify the mechanism of biofilm formation, drug resistance in biofilm and the antifungalmechanisms is still necessary. Metabolomics, the systems biology approach of smallmolecules, has been widely used in the fields of microbiology, botany, disease diagnosisand commonly defined as “the quantitative measurement of the dynamic multiparametric response of a living system to pathophysiological stimuli or genetic manipulations”.Here, we present gas chromatography coupled to mass spectrometry (GC/MS)-basedmetabolomics study of the biofilm and planktonic mode of C. albicans growth，metabolomics study of with or without Amphotericin B or miconazole and the study ofshikonin. Our purpose is to analyze metabolite profiles between the biofilm and planktonicforms of C. albicans at each grown phase, metabolite profiles with C. albicans with orwithout Amphotericin B or miconazole and metabolite profiles with shikonin. Theycontributed to the elucidation of the complex pathogenic mechanism of C. albicans, whichmay shed new light upon C. albicans biofilm and the development of new antifungalagents.