Dataset Information

Synergistic Effects and Mechanisms of Combined Treatment With Harmine Hydrochloride and Azoles for Resistant Candida albicans.

ABSTRACT: Several studies have demonstrated the significant antiviral, antimicrobial, antiplasmodial, antioxidative, antifungal, antimutagenic, and antitumor properties of harmine hydrochloride (HMH). The main objective of the present study was to investigate the antifungal effects and underlying mechanisms of HMH when combined with azoles to determine whether such combinations act in a synergistic manner. As a result, we found that HMH exhibits synergistic antifungal effects in combination with azoles against resistant Candida albicans (C. albicans) planktonic cells, as well as resistant C. albicans biofilm in the early stage. Antifungal potential of HMH with fluconazole was also explored in vivo using an invertebrate model. Our results suggest that HMH combined with azoles is synergistic against resistant C. albicans in vitro and in vivo. No synergy is seen with azole sensitive C. albicans strains nor with other Candida species. Such synergistic mechanisms on resistance C. albicans are involved in increasing intracellular azoles, inhibiting hyphal growth, disturbing cytosolic calcium concentration, and inducing apoptosis of resistant C. albicans cells.

SUBMITTER: Li X

PROVIDER: S-EPMC6843067 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Synergistic Effects and Mechanisms of Combined Treatment With Harmine Hydrochloride and Azoles for Resistant <i>Candida albicans</i>.

Li Xiuyun X Wu Xuexin X Gao Yan Y Hao Lina L

Frontiers in microbiology 20191015

Several studies have demonstrated the significant antiviral, antimicrobial, antiplasmodial, antioxidative, antifungal, antimutagenic, and antitumor properties of harmine hydrochloride (HMH). The main objective of the present study was to investigate the antifungal effects and underlying mechanisms of HMH when combined with azoles to determine whether such combinations act in a synergistic manner. As a result, we found that HMH exhibits synergistic antifungal effects in combination with azoles ag ...[more]

PMID: 31749766

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Project description:Resistance to azole antifungals continues to be a significant problem in the common fungal pathogen Candida albicans. Many of the molecular mechanisms of resistance have been defined with matched sets of susceptible and resistant clinical isolates from the same strain. Mechanisms that have been identified include alterations in the gene encoding the target enzyme ERG11 or overexpression of efflux pump genes including CDR1, CDR2, and MDR1. In the present study, a collection of unmatched clinical isolates of C. albicans was analyzed for the known molecular mechanisms of resistance by standard methods. The collection was assembled so that approximately half of the isolates were resistant to azole drugs. Extensive cross-resistance was observed for fluconazole, clotrimazole, itraconazole, and ketoconazole. Northern blotting analyses indicated that overexpression of CDR1 and CDR2 correlates with resistance, suggesting that the two genes may be coregulated. MDR1 overexpression was observed infrequently in some resistant isolates. Overexpression of FLU1, an efflux pump gene related to MDR1, did not correlate with resistance, nor did overexpression of ERG11. Limited analysis of the ERG11 gene sequence identified several point mutations in resistant isolates; these mutations have been described previously. Two of the most common point mutations in ERG11 associated with resistance, D116E and E266D, were tested by restriction fragment length polymorphism analysis of the isolates from this collection. The results indicated that the two mutations occur frequently in different isolates of C. albicans and are not reliably associated with resistance. These analyses emphasize the diversity of mechanisms that result in a phenotype of azole resistance. They suggest that the resistance mechanisms identified in matched sets of susceptible and resistant isolates are not sufficient to explain resistance in a collection of unmatched clinical isolates and that additional mechanisms have yet to be discovered.

Dataset Information

Synergistic Effects and Mechanisms of Combined Treatment With Harmine Hydrochloride and Azoles for Resistant Candida albicans.

Publications

Synergistic Effects and Mechanisms of Combined Treatment With Harmine Hydrochloride and Azoles for Resistant <i>Candida albicans</i>.

Similar Datasets

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