title: Lysine enhances the effect of amphotericin B against Candida albicans in vitro.
abstract: Amphotericin B (AmB) is a polyene antibiotic produced by Streptomyces nodosus and has been used for >50 years in the treatment of acute systemic fungal infections. In the present study, we demonstrated that lysine, an essential amino acid, could enhance the effect of AmB against Candida albicans in vitro, although lysine itself did not exert a fungicidal effect. In addition, the combination of AmB with lysine could provide an enhanced action against Candida parapsilosis and Cryptococcus neoformans compared with AmB alone. Lysine could also enhance the antifungal effect of caspofungin or nystatin. An enhanced effect of the combination of lysine with AmB was observed for the prevention of biofilm and hypha formation. Furthermore, our results demonstrated that lysine-mediated oxidative damage, such as the generation of endogenous reactive oxygen species, may be the mechanism underlying the enhancing effect of lysine on AmB. Our results also showed that CaMCA1 gene plays an important role in increasing the sensitivity of C. albicans cells upon AmB treatment. Using AmB together with lysine may be a promising strategy for the therapy of disseminated candidiasis.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China Pharmacy Department, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Liuya
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Liao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China 13761571578@163.com caoyingying608@163.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China 13761571578@163.com caoyingying608@163.com.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D058365:Candidiasis, Invasive / Q000188:drug therapy; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D005800:Genes, Fungal / Q000187:drug effects; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D066298:In Vitro Techniques; D008239:Lysine / Q000008:administration & dosage*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D017382:Reactive Oxygen Species; D000666:Amphotericin B; D008239:Lysine
keywords: Candida albicans; amphotericin B; biofilm; lysine; reactive oxygen species