Chemosensitization of fungal pathogens to antimicrobial agents using benzo analogs

Kim, Jong H.; Mahoney, Noreen; Chan, Kathleen L.; Molyneux, Russell J.; May, Gregory S.; Campbell, Bruce

doi:10.1111/j.1574-6968.2008.01072.x

Cited by 35 publications

(51 citation statements)

References 37 publications

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“…However, when ROS defense system be weakened or inactivated, the same amount ZnO NPs could exhibit higher toxicity to fungi cells. The mode of thiram action was thought to be a complex process, one of its fungicide effects was considered as the depletion of glutathione (GSH)44 and intracellular inactivation of glutathione reductase45 due to the disulfide bridge in the thiram structure. GSH plays an important role in cellular life-activity, it has been reported to protect cells against the destructive effects of oxidative stress caused by ROS46.…”

Section: Discussionmentioning

confidence: 99%

A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

Xue

Luo

et al. 2014

Sci Rep

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Here we reported a residue-free green nanotechnology which synergistically enhance the pesticides efficiency and successively eliminate its residue. We built up a composite antifungal system by a simple pre-treating and assembling procedure for investigating synergy. Investigations showed 0.25 g/L ZnO nanoparticles (NPs) with 0.01 g/L thiram could inhibit the fungal growth in a synergistic mode. More importantly, the 0.25 g/L ZnO NPs completely degraded 0.01 g/L thiram under simulated sunlight irradiation within 6 hours. It was demonstrated that the formation of ZnO-thiram antifungal system, electrostatic adsorption of ZnO NPs to fungi cells and the cellular internalization of ZnO-thiram composites played important roles in synergy. Oxidative stress test indicated ZnO-induced oxidative damage was enhanced by thiram that finally result in synergistic antifungal effect. By reducing the pesticides usage, this nanotechnology could control the plant disease economically, more significantly, the following photocatalytic degradation of pesticide greatly benefit the human social by avoiding negative influence of pesticide residue on public health and environment.

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Section: Discussionmentioning

confidence: 99%

A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

Xue

Luo

et al. 2014

Sci Rep

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“…For example, increased activity of amphotericin B against Aspergillus fumigatus could be achieved by coincubation with thymol, the latter acting on the osmotic/oxidative stress mitogen-activated protein kinase (MAPK) pathway via SakA (6). Additionally, increased activity of fludioxonil, strobilurin, and antimycin A (antifungals targeting the oxidative and osmotic stress response systems) against various yeasts and filamentous fungi was obtained using certain benzaldehydes and benzoic acids (7). In Saccharomyces cerevisiae, tolerance to 2,3-dihydroxybenzaldehyde or 2,3-dihydroxybenzoic acid was found to rely upon mitochondrial superoxide dismutase (SOD2) or glutathione reductase (GLR1), respectively (7).…”

Section: Discussionmentioning

confidence: 99%

Superoxide Dismutases Are Involved in Candida albicans Biofilm Persistence against Miconazole

Bink

Vandenbosch

Coenye

et al. 2011

Antimicrob Agents Chemother

109

104

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We investigated the cellular mechanisms responsible for the occurrence of miconazole-tolerant persisters in Candida albicans biofilms. Miconazole induced about 30% killing of sessile C. albicans cells at 75 M. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2%. Since miconazole induces reactive oxygen species (ROS) in sessile C. albicans cells, we focused on a role for superoxide dismutases (Sods) in persistence and found the expression of Sod-encoding genes in sessile C. albicans cells induced by miconazole compared to the expression levels in untreated sessile C. albicans cells. Moreover, addition of the superoxide dismutase inhibitor N,N-diethyldithiocarbamate (DDC) to C. albicans biofilms resulted in an 18-fold reduction of the miconazole-tolerant persister fraction and in increased endogenous ROS levels in these cells. Treatment of biofilms of C. albicans clinical isolates with DDC resulted in an 18-fold to more than 200-fold reduction of their miconazole-tolerant persister fraction. To further confirm the important role for Sods in C. albicans biofilm persistence, we used a ⌬sod4 ⌬sod5 mutant lacking Sods 4 and 5. Biofilms of the ⌬sod4 ⌬sod5 mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels compared to biofilms of the isogenic wild type (WT). In conclusion, the occurrence of miconazole-tolerant persisters in C. albicans biofilms is linked to the ROS-detoxifying activity of Sods. Moreover, Sod inhibitors can be used to potentiate the activity of miconazole against C. albicans biofilms.

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“…This generally entails the use of recognized antifungal agents for which complementary mechanisms of action have been proven (8,12). In recent years, however, the concept of chemosensitization of fungal organisms to standard antifungal agents (e.g., azoles) by exposure to biological agents or nontraditional partner drugs, such as nitric oxide, cyclosporine, benzo analogues, or recombinant antibodies, has emerged (13,15,18,19,23). Each of these agents may alter the ability of fungal cells to respond or adapt to the insult of a specific antifungal exposure.…”

Section: Resultsmentioning

confidence: 99%

Activity of MGCD290, a Hos2 Histone Deacetylase Inhibitor, in Combination with Azole Antifungals against Opportunistic Fungal Pathogens

Pfaller¹,

Messer²,

et al. 2009

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We report on the in vitro activity of the Hos2 fungal histone deacetylase (HDAC) inhibitor MGCD290 (MethylGene, Inc.) in combination with azoles against azole-resistant yeasts and molds. Susceptibility testing was performed by the CLSI M27-A3 and M38-A2 broth microdilution methods. Testing of the combinations (MGCD290 in combination with fluconazole, posaconazole, or voriconazole) was performed by the checkerboard method. The fractional inhibitory concentrations were determined and were defined as <0.5 for synergy, >0.5 but <4 for indifference, and >4 for antagonism. Ninety-one isolates were tested, as follows: 30 Candida isolates, 10 Aspergillus isolates, 15 isolates of the Zygomycetes order, 10 Cryptococcus neoformans isolates, 8 Rhodotorula isolates, 8 Fusarium isolates, 5 Trichosporon isolates, and 5 Scedosporium isolates. MGCD290 showed modest activity when it was used alone (MICs, 1 to 8 g/ml) and was mostly active against azoleresistant yeasts, but the MICs against molds were high (16 to >32 g/ml).

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Chemosensitization of fungal pathogens to antimicrobial agents using benzo analogs

Cited by 35 publications

References 37 publications

A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

Superoxide Dismutases Are Involved in Candida albicans Biofilm Persistence against Miconazole

Activity of MGCD290, a Hos2 Histone Deacetylase Inhibitor, in Combination with Azole Antifungals against Opportunistic Fungal Pathogens

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