scholarly journals The fungicidal activity of amphotericin B requires autophagy-dependent targeting to the vacuole under a nutrient-starved condition in Saccharomyces cerevisiae

Microbiology ◽  
2016 ◽  
Vol 162 (5) ◽  
pp. 848-854 ◽  
Author(s):  
Michiru Yoshioka ◽  
Keiichi Yamada ◽  
Yoshihiro Yamaguchi ◽  
Akira Ogita ◽  
Ken-ichi Fujita ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amphotericin B ◽  
Fungicidal Activity

Visualization analysis of the vacuole-targeting fungicidal activity of amphotericin B against the parent strain and an ergosterol-less mutant of Saccharomyces cerevisiae

Microbiology ◽  
2013 ◽  
Vol 159 (Pt_5) ◽  
pp. 939-947 ◽  
Author(s):  
Chang-Kyung Kang ◽  
Keiichi Yamada ◽  
Yoshinosuke Usuki ◽  
Akira Ogita ◽  
Ken-ichi Fujita ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amphotericin B ◽  
Parent Strain ◽  
Fungicidal Activity ◽  
Visualization Analysis

Stable Phenotypic Resistance of CandidaSpecies to Amphotericin B Conferred by Preexposure to Subinhibitory Levels of Azoles

1998 ◽  
Vol 36 (9) ◽  
pp. 2690-2695 ◽  
Author(s):  
Jose A. Vazquez ◽  
Maria T. Arganoza ◽  
Dina Boikov ◽  
Stephanie Yoon ◽  
Jack D. Sobel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Clinical Setting ◽  
Fungicidal Activity ◽  
No Reduction ◽  
Growth Conditions ◽  
In Vitro Assays ◽  
In Vitro Susceptibility ◽  
Phenotypic Resistance ◽  
Time Period

The fungicidal activity of amphotericin B (AmB) was quantitated for several Candida species. Candida albicans andC. tropicalis were consistently susceptible to AmB, with less than 1% survivors after 6 h of exposure to AmB. C. parapsilosis and variants of C. lusitaniae andC. guilliermondii were the most resistant, demonstrating 50 to 90% survivors in this time period and as high as 1% survival after a 24-h exposure time. All Candida species were killed (<1% survivors) after 24 h of exposure to AmB. In contrast, overnight exposure to either fluconazole or itraconazole resulted in pronounced increases in resistance to subsequent exposures to AmB. Most dramatically, C. albicans was able to grow in AmB cultures after azole preexposure. Several other Candida species did not grow in AmB but showed little or no reduction in viability after up to 24 h in AmB. Depending on the growth conditions,Candida cells preexposed to azoles may retain AmB resistance for days after the azoles have been removed. If this in vitro antagonism applies to the clinical setting, treatment of patients with certain antifungal combinations may not be beneficial. The ability of some Candida isolates to survive transient exposures to AmB was not reflected in the in vitro susceptibility changes as measured by standard MIC assays. This finding should be considered in studies attempting to correlate patient outcome with in vitro susceptibilities of clinical fungal isolates. Patients who fail to respond to AmB may be infected with isolates that are classified as susceptible by standard in vitro assays but that may be resistant to transient antifungal exposures which may be more relevant in the clinical setting.

scholarly journals Assessment of Candida auris Response to Antifungal Drugs Using Time–Kill Assays and an Animal Model

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S73-S73 ◽  
Author(s):  
Ronen Ben-Ami ◽  
Liat Ashkenazi ◽  
Judith Berman ◽  
Nuphar Korolker ◽  
Anna Novikov
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity ◽  
Antifungal Drugs ◽  
Rank Test ◽  
Infection Model ◽  
Candida Auris ◽  
Fungistatic Activity ◽  
Kill Curve ◽  
Time Kill

Abstract Background Candida auris is an emerging nosocomial pathogen that is resistant to Fluconazole and variably susceptible to other systemic drug classes. Treatment with echinocandins has been recommended based on MICs in the susceptible range, but supporting in vivo data is lacking. Methods We tested the MIC of C. auris strains (n = 12) to fluconazole, voriconazole, posaconazole. anidulafungin, amphotericin B and flucytosine. Representative C. auris strains from Israel and South Africa, and a reference C. albicans strain were analysed using time–kill curve assays. Fungicidal activity was defined as reduction of ≥3 log from baseline CFU/ml. Response to caspofungin treatment was assessed in BALB/c mice immunosuppressed with cyclophosphamide and inoculated with 7 × 107C. auris cells by tail vein injection. Mice were treated from day +1 to day +7 with caspofungin (IP) at doses of 1 or 5 mg/kg and compared with sham-treated controls. Survival was assessed daily. Kaplan-Meier survival analyses were performed and treatment arms were compared using the log-rank test. Results Drug susceptibility results (MIC50 and MIC90) were: fluconazole, 64 and 128 mg/l; voriconazole, 0.5 and 24 mg/l; posaconazole, 0.5 and 27 mg/l; anidulafungin, 0.03 and 0.06 mg/l; amphotericin B, 2 and 8 mg/l; flucytosine, 0.3 and 1 mg/l. Time–kill curve analyses showed log reduction from baseline CFU concentration of −3.0 to −2.8 for fluconazole (MIC ×1), 5.6–6.1 for amphotericin B (MIC ×4) and −0.4 to −0.9 for caspofungin (MIC ×16), consistent with fungicidal activity of amphotericin B and weak fungistatic activity of caspofungin. In the mouse model, survival rate was similar with sham treatment (33%) and treatment with caspofungin 1 mg/kg/day (44%) and 5 mg/kg/day (22%), P = 0.7. Conclusion Despite generally low MIC, caspofungin has only mild fungistatic activity on C. auris and no effect on survival in a mouse infection model. Amphotericin B has fungicidal activity against C. auris. Disclosures All authors: No reported disclosures.

A comparison of the fungicidal activity of amphotericin B and posaconazole against Zygomycetes in vitro

2009 ◽  
Vol 63 (4) ◽  
pp. 361-364 ◽  
Author(s):  
Suganthini Krishnan-Natesan ◽  
Elias K. Manavathu ◽  
George J. Alangaden ◽  
Pranatharthi H. Chandrasekar
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity

Enhancement of the Fungicidal Activity of Amphotericin B by Allicin: Effects on Intracellular Ergosterol Trafficking

Planta Medica ◽  
2008 ◽  
Vol 75 (03) ◽  
pp. 222-226 ◽  
Author(s):  
Akira Ogita ◽  
Ken-ichi Fujita ◽  
Toshio Tanaka
Keyword(s):  
Amphotericin B ◽  
Fungicidal Activity
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