Effect of Tetrandrine against Candida albicans Biofilms

Zhao, Lijie; Li, Dedong; Hu, Dandan; Hu, Guang; Yan, Lan; Wang, Yan; Jiang, Yuanying

doi:10.1371/journal.pone.0079671

Cited by 58 publications

(56 citation statements)

References 73 publications

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“…6C and D) (Sudbery, 2011). In addition, some regulators of the MAPK cascade (Zhao et al ., 2013), such as HST7, CEK1 and CPH1, were also downregulated by the exogenous addition of compound 28e (Fig. 6C and D).…”

Section: Resultsmentioning

confidence: 85%

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

Zhao

Huang

Sun

et al. 2018

Microbial Biotechnology

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SummaryClinical treatment of Candida albicans infections has become more difficult due to the limited development of antifungal agents and the rapid emergence of drug resistance. In this study, we demonstrate the synthesis of a series of piperazine derivatives and the evaluation of their inhibitory activity against C. albicans virulence. Thirty‐four (1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives, including 25 new compounds, were synthesized and assessed for their efficacy against the physiology and pathogenesis of C. albicans. Several compounds strongly inhibited the morphological transition and virulence of C. albicans cells, although they did not influence the growth rate of the fungal pathogen. A leading novel compound, (1‐(4‐ethoxyphenyl)‐4‐(1‐biphenylol‐2‐hydroxypropyl)‐piperazine), significantly attenuated C. albicans virulence by interfering with the process of hyphal development, but it showed no cytotoxicity against human cells at a micromolar level. These findings suggest that (1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives could potentially be developed as novel therapeutic agents for the clinical treatment of C. albicans infections by interfering with morphological transition and virulence.

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Section: Resultsmentioning

confidence: 85%

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

Zhao

Huang

Sun

et al. 2018

Microbial Biotechnology

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“…Since SAN could inhibit adhesion and hypha formation, we detected the expression of some well-known genes (18,19) involved in adhesion and filamentation (Fig. 5A).…”

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confidence: 99%

Activity of Sanguinarine against Candida albicans Biofilms

Zhong

et al. 2017

Antimicrob Agents Chemother

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Candida albicans biofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process of C. albicans infections. New antifungal agents against C. albicans biofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity against Candida albicans biofilms and explore the underlying mechanism. The MIC 50 of SAN was 3.2 g/ ml, while Ն0.8 g/ml of SAN could suppress C. albicans biofilms. Further study revealed that Ն0.8 g/ml of SAN could decrease cellular surface hydrophobicity (CSH) and inhibited hypha formation. Real-time reverse transcription-PCR (RT-PCR) results indicated that the exposure of C. albicans to SAN suppressed the expression of some adhesion-and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, including ALS3, HWP1, ECE1, HGC1, and CYR1. Consistently, the endogenous cAMP level of C. albicans was downregulated after SAN treatment, and the addition of cAMP rescued the SAN-induced filamentation defect. In addition, SAN showed relatively low toxicity to human umbilical vein endothelial cells, the 50% inhibitory concentration (IC 50 ) being 7.8 g/ml. Collectively, the results show that SAN exhibits strong activity against C. albicans biofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.

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“…After treatment with hexamethyldisilazane (Polysciences Europe GmbH, Eppelheim, Germany), the samples were dried overnight. The specimens were coated with gold and observed through a Carl Zeiss SEM (EVO LS10) in high-vacuum mode (27,74).…”

Section: Methodsmentioning

confidence: 99%

“…Cellular surface hydrophobicity (CSH) was measured by using a water-hydrocarbon two-phase assay as described earlier (28,74). In brief, the preformed C. albicans biofilms were removed from the flask surface to obtain a cell suspension (OD 600 , 1.0 in YPD medium).…”

Section: Methodsmentioning

confidence: 99%

In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans

Liu

Shang

et al. 2017

Antimicrob Agents Chemother

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Formyl-phloroglucinol meroterpenoids (FPMs) are important types of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the Eucalyptus robusta-derived FPMs, eucarobustol E (EE), exerted a strong inhibitory effect against Candida albicans biofilms at a concentration of 16 g/ml. EE was found to block the yeast-to-hypha transition and reduce the cellular surface hydrophobicity of the biofilm cells. RNA sequencing and real-time reverse transcription-PCR analysis showed that exposure to 16 g/ml of EE resulted in marked reductions in the levels of expressions of genes involved in hyphal growth (EFG1, CPH1, TEC1, EED1, UME6, and HGC1) and cell surface protein genes (ALS3, HWP1, and SAP5). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were downregulated, while the farnesol-encoding gene (DPP3) was upregulated, and these findings were in agreement with those from the quantification of ergosterol and farnesol. Combined with the obvious elevation of negative regulator genes (TUP1, NRG1), we speculated that EE's inhibition of carbon flow to ergosterol triggered the mechanisms of the negative regulation of hyphal growth and eventually led to biofilm inhibition.

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Effect of Tetrandrine against Candida albicans Biofilms

Cited by 58 publications

References 73 publications

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

(1‐aryloxy‐2‐hydroxypropyl)‐phenylpiperazine derivatives suppress Candida albicans virulence by interfering with morphological transition

Activity of Sanguinarine against Candida albicans Biofilms

In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans

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