Amphotericin B

Amphotericin B, a polyene antifungal antibiotic, has been produced from a strain of Streptomyces nodosus with an IC50 of 0.028–0.290 μg/ml.

In vitro: Amphotericin B was the most effective drug for treating many life-threatening fungal infections. In cells expressing TLR2 and CD14, amphotericin B induced signal transduction and inflammatory cytokine release. In primary murine macrophages and human cell lines expressing TLR2, CD14, and the adapter protein MyD88, amphotericin induced NF-κB-dependent reporter activity and cytokine release, whereas cells deficient in any of these failed to respond. Cells with TLR4 mutation were less responsive to amphotericin B stimulation than cells expressing normal TLR4 [1]. Amphotericin B could interact with cholesterol, the major sterol of mammal membranes, thus limiting the usefulness of Amphotericin B due to its relatively high toxicity [2]. Low AmB concentrations (≤ 0.1 μM) induced a polarization potential in KCl-loaded liposomes suspended in an iso-osmotic sucrose solution, indicating K+ leakage. AmB (＞ 0.1 μM) allowed cations and anions movements. LPs suspended in an iso-osmotic NaCl solution and exposed to AmB (0.05 μM) exhibited a nearly total collapse of the negative membrane potential, indicated that Na+ entered into the cells [3].

In vivo: Amphotericin B prolonged the incubation time and decreased PrPSc accumulation in the hamster scrapie model. Amphotericin B markedly resulted in reduction of PrPSc levels in mice with transmissible subacute spongiform encephalopathies (TSSE) [4].

两性霉素B是一种多烯类抗真菌抗生素，由结节链霉菌菌株产生，其IC50为0.028–0.290μg/ml。

体外：两性霉素B是治疗许多危及生命的真菌感染最有效的药物。在表达TLR2和CD14的细胞中，两性霉素B诱导信号转导和炎性细胞因子释放。在表达TLR2、CD14和衔接蛋白MyD88的原代鼠巨噬细胞和人细胞系中，两性霉素诱导NF-κB依赖性报告基因活性和细胞因子释放，而缺乏任何这些的细胞都没有反应。与表达正常TLR4的细胞相比，具有TLR4突变的细胞对两性霉素B刺激的反应较弱[1]。两性霉素B可能与哺乳动物膜的主要固醇胆固醇相互作用，因此由于其相对较高的毒性而限制了两性霉素的用途[2]。

低AmB浓度（≤0.1μM）在悬浮于等渗蔗糖溶液中的KCl负载脂质体中诱导极化电位，表明K+渗漏。AmB（＞0.1μM）允许阳离子和阴离子运动。悬浮在等渗NaCl溶液中并暴露于AmB（0.05μM）的LPs表现出负膜电位几乎完全崩溃，表明Na+进入细胞[3]。

体内：两性霉素B延长了仓鼠瘙痒模型中的孵育时间并减少了PrPSc的积累。两性霉素B可显著降低传播性亚急性海绵状脑病（TSSE）小鼠的PrPSc水平[4]。

References:
[1]. Sau K1,Mambula SS,Latz E,Henneke P,Golenbock DT,Levitz SM.The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism.J Biol Chem.2003 Sep 26;278(39):37561-8. Epub 2003 Jul 14.
[2]. Barwicz J1,Tancrède P.The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers.Chem Phys Lipids.1997 Feb 28;85(2):145-55.
[3]. Ramos H1,Valdivieso E,Gamargo M,Dagger F,Cohen BE.Amphotericin B kills unicellular leishmanias by forming aqueous pores permeable to small cations and anions.J Membr Biol.1996 Jul;152(1):65-75.
[4]. Demaimay R1,Adjou K,Lasmézas C,Lazarini F,Cherifi K,Seman M,Deslys JP,Dormont D.Pharmacological studies of a new derivative of amphotericin B, MS-8209, in mouse and hamster scrapie.J Gen Virol.1994 Sep;75 ( Pt 9):2499-503.