scholarly journals Dependence of vacuole disruption and independence of potassium ion efflux in fungicidal activity induced by combination of amphotericin B and allicin against Saccharomyces cerevisiae

2010 ◽  
Vol 63 (12) ◽  
pp. 689-692 ◽  
Author(s):  
Akira Ogita ◽  
Masahiro Yutani ◽  
Ken-ichi Fujita ◽  
Toshio Tanaka
Microbiology ◽  
2013 ◽  
Vol 159 (Pt_5) ◽  
pp. 939-947 ◽  
Author(s):  
Chang-Kyung Kang ◽  
Keiichi Yamada ◽  
Yoshinosuke Usuki ◽  
Akira Ogita ◽  
Ken-ichi Fujita ◽  
...  

Microbiology ◽  
2016 ◽  
Vol 162 (5) ◽  
pp. 848-854 ◽  
Author(s):  
Michiru Yoshioka ◽  
Keiichi Yamada ◽  
Yoshihiro Yamaguchi ◽  
Akira Ogita ◽  
Ken-ichi Fujita ◽  
...  

1998 ◽  
Vol 36 (9) ◽  
pp. 2690-2695 ◽  
Author(s):  
Jose A. Vazquez ◽  
Maria T. Arganoza ◽  
Dina Boikov ◽  
Stephanie Yoon ◽  
Jack D. Sobel ◽  
...  

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.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S73-S73 ◽  
Author(s):  
Ronen Ben-Ami ◽  
Liat Ashkenazi ◽  
Judith Berman ◽  
Nuphar Korolker ◽  
Anna Novikov

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.


1999 ◽  
Vol 181 (22) ◽  
pp. 6876-6881 ◽  
Author(s):  
Andreas Anton ◽  
Cornelia Große ◽  
Jana Reißmann ◽  
Thomas Pribyl ◽  
Dietrich H. Nies

ABSTRACT The Czc system of Ralstonia sp. strain CH34 mediates resistance to cobalt, zinc, and cadmium through ion efflux catalyzed by the CzcCB2A cation-proton antiporter. The CzcD protein is involved in the regulation of the Czc system. It is a membrane-bound protein with at least four transmembrane α-helices and is a member of a subfamily of the cation diffusion facilitator (CDF) protein family, which occurs in all three domains of life. The deletion ofczcD in a Ralstonia sp. led to partially constitutive expression of the Czc system due to an increased transcription of the structural czcCBA genes, both in the absence and presence of inducers. The czcD deletion could be fully complemented in trans by CzcD and two other CDF proteins from Saccharomyces cerevisiae, ZRC1p and COT1p. All three proteins mediated a small but significant resistance to cobalt, zinc, and cadmium in Ralstonia, and this resistance was based on a reduced accumulation of the cations. Thus, CzcD appeared to repress the Czc system by an export of the inducing cations.


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

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