Amphotericin B, Solubilized

- Overview
  - Amphotericin B, Solubilized is a polyene macrolide aminoglycoside broad-spectrum antimycotic. This bioactive natural product was isolated from soil collected from Orinoco River (Venezuela) in 1955 and identified as Streptomyces nodosus by Squibb Institute for Medical Research. It is used to control contamination from fungi, viruses and protozoa and a common media selective agent to inhibit the growth of background fungi. It also has immunomodulatory properties. The product is formulated with sodium deoxycholate to maximize the solubility.
    In the face of the global COVID-19 pandemic, the Centers for Disease Control (CDC) Standard Operating Procedure (SOP) DSR-052-04 includes the addition of Amphotericin B to viral transport media for SARS-CoV2 samples.
    
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    Background
    
    Amphotericin B associates with membrane sterols (ergosterol in fungal cell membranes, and cholesterol in mammalian cell membranes). Amphotericin B forms a pore in these membranes resulting in leakage of essential ions and ultimately cell death.
    Acquired resistance is very low, but is achieved indifferent ways. Some studies with biofilms have found it is due to decrease in ergosterol content and changes in the cell wall.
    Amphotericin B can modulates the immune system. It also induces the accumulation of nitric oxide and ROIs.
- Properties
  - CAS Number
    
    1397-89-3 (Amphotericin B)
    
    Molecular Formula
    
    C47H73NO17 (Amphotericin B)
    
    Molecular Weight
    
    924.08 (Amphotericin B)
    
    Appearance
    
    Yellow or orange powder
    
    Solubility
    
    0.05% in H2O: hazy yellow solution
    
    Other Properties
    
    Source: Streptomyces nodosus
    Assay: (As Is): ≥240 µg/mg
    
    Storage
    
    2-8°C
    
    * For research use only
- Applications
  - Application Description
    
    Spectrum: Amphotericin B is active against mammalian cells, fungi, viruses, and protozoa. Amphotericin B is not toxic to bacteria or viruses due to their lack of sterols.
    
    Microbiology Applications: Amphotericin B is used as an antimycotic selective agent in several routinely used selective media formulations to inhibit the growth of background fungal growth.
    According to the CDC SOP (DSR-052-04) for Viral Transport Medium (VTM), Amphotericin B is used at a final concentration of 0.5 µg/ml. Stock solution concentration is 250 µg/ml.
    While the toxicity of Amphotericin B in mammalian cells is associated with an increase in intracellular calcium, in Candida albicans, it is not dependent on increased movement of calcium across the cell membrane or the presence of extracellular calcium (Rogers et al, 2003).
    The isolation of influenza A and B viruses can be dramatically enhanced by adding Amphotericin B to the culture medium. It promotes viral uptake and endocytic processing of the virus particles (Roethl E et al (2011).
    The following represents MIC susceptibility data for Amphotericin B against common fungal pathogens:
    Candida albicans - 0.001 - 321 μg/ml
    Candida krusei - 0.001 - 16 μg/ml
    Coccidioides immitis - 0.0625 - 2 μg/ml
    Cryptococcus neoformans - 0.2 - 39 μg/ml
    Fusarium oxysporum - 0.75 - 125 μg/ml
    
    Plant Biology Applications: Amphotericin B can be used to inhibit phytopathogenic fungi in vitro
    
    Eukaryotic Cell Culture Applications: Amphotericin B can be used in eukaryotic cell culture to control or prevent contamination from fungi, viruses, and protozoa. Amphotericin B can be toxic to cell lines at high concentrations and should not be used at concentrations greater than 2.50 µg/mL. Amphotericin B has been used in vitro to inhibit the generation of the scrapie isoform of the prion protein when studying transmissible spongiform encephalopathies (Mangé et al 2000).
    Amphotericin B stimulates transcription and production of multiple mediators of the immune system (such as cytokines, chemokines, and prostaglandins) and ICAM-1 in murine and human cells (Arango et al, 2012).