1887

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Volume 63, Issue 7

Synergistic mechanism for tetrandrine on fluconazole against through the mitochondrial aerobic respiratory metabolism pathway Free

Abstract

We found that tetrandrine (TET) can reverse the resistance of to fluconazole (FLC) and that this interaction is associated with the inhibition of drug efflux pumps. Mitochondrial aerobic respiration, which plays a major role in metabolism, is the primary source of ATP for cellular processes, including the activation of efflux pumps. However, it was unclear if TET exerts its synergistic action against via its impact on the mitochondrial aerobic respiratory metabolism. To investigate this mechanism, we examined the impact of FLC in the presence or absence of TET on two strains obtained from a single parental source (FLC-sensitive strain CA-1 and FLC-resistant strain CA-16). We analysed key measures of energy generation and conversion, including the activity of respiration chain complexes I and III (CI and CIII), ATP synthase (CV) activity, and the generation of reactive oxygen species (ROS), and studied intracellular ATP levels and the mitochondrial membrane potential (ΔΨ), which has a critical impact on energy transport. Mitochondrial morphology was observed by confocal microscopy. Our functional analyses revealed that, compared with strains treated only with FLC, TET+FLC increased the ATP levels and decreased ΔΨ in CA-1, but decreased ATP levels and increased ΔΨ in CA-16 (<0.05). Additionally, CI, CIII and CV activity decreased by 23–48 %. The production of ROS increased by two- to threefold and mitochondrial morphology was altered in both strains. Our data suggested that TET impacted mitochondrial aerobic respiratory metabolism by influencing the generation and transport of ATP, reducing the utilization of ATP, and resulting in the inhibition of drug efflux pump activity. This activity contributed to the synergistic action of TET on FLC against .

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© 2014 The Authors
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2014-07-01
2024-04-18
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Synergistic mechanism for tetrandrine on fluconazole against Candida albicans through the mitochondrial aerobic respiratory metabolism pathway
J. Med. Microbiol. 63, 988 (2014); https://doi.org/10.1099/jmm.0.073890-0
/content/journal/jmm/10.1099/jmm.0.073890-0
/content/journal/jmm/10.1099/jmm.0.073890-0
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