Growth of Candida albicans hyphae

Sudbery, Peter E.

doi:10.1038/nrmicro2636

Cited by 934 publications

(1,033 citation statements)

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“…Real‐time PCR analysis showed that exogenous addition of the leading compound 28e inhibited the expression levels of CDC35, EFG1, TEC1 and HWP1, which are regulators involved in the cAMP‐PKA pathways (Fig. 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.…”

Section: Resultsmentioning

confidence: 99%

(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: 99%

(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 FLZ interferes with the ergosterol pathway and ergosterol is necessary for hyphae formation, the presence of FLZ inhibits the transition from yeast to hypha [48], even in a culture medium that promotes C. albicans filamentous morphology. Thus, taking into consideration that hypha is the invasive form of C. albicans [49], the reduction of its size in both CaS and CaR is an important result in the decrease of the virulence of this strain. In addition, FLZ significantly reduced the CFU/mL in CgS and CgR (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

Panariello

Klein

Mima

et al. 2018

Journal of Oral Microbiology

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Background: Fluconazole (FLZ) is a drug commonly used for the treatment of Candida infections. However, β-glucans in the extracellular matrices (ECMs) hinder FLZ penetration into Candida biofilms, while extracellular DNA (eDNA) contributes to the biofilm architecture and resistance. Methods: This study characterized biofilms of FLZ-sensitive (S) and -resistant (R) Candida albicans and Candida glabrata in the presence or absence of FLZ focusing on the ECM traits. Biofilms of C. albicans American Type Culture Collection (ATCC) 90028 (CaS), C. albicans ATCC 96901 (CaR), C. glabrata ATCC 2001 (CgS), and C. glabrata ATCC 200918 (CgR) were grown in RPMI medium with or without FLZ at 5× the minimum inhibitory concentration (37°C/48 h). Biofilms were assessed by colony-forming unit (CFU)/mL, biomass, and ECM components (alkali-soluble polysaccharides [ASP], water-soluble polysaccharides [WSP], eDNA, and proteins). Scanning electron microscopy (SEM) was also performed. Data were analyzed by parametric and nonparametric tests (α = 0.05). Results: In biofilms, FLZ reduced the CFU/mL of all strains (p < 0.001), except for CaS (p = 0.937). However, the ASP quantity in CaS was significantly reduced by FLZ (p = 0.034), while the drug had no effect on the ASP levels in other strains (p > 0.05). Total biomasses and WSP were significantly reduced by FLZ in the ECM of all yeasts (p < 0.001), but levels of eDNA and proteins were unaffected (p > 0.05). FLZ affected the cell morphology and biofilm structure by hindering hyphae formation in CaS and CaR biofilms, by decreasing the number of cells in CgS and CgR biofilms, and by yielding sparsely spaced cell agglomerates on the substrate. Conclusion: FLZ impacts biofilms of C. albicans and C. glabrata as evident by reduced biomass. This reduced biomass coincided with lowered cell numbers and quantity of WSPs. Hyphal production by C. albicans was also reduced.

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“…The success of C. albicans as a major fungal pathogen of humans relies on a number of pathogenic traits, among which its capacity to grow and switch between at least three distinctive morphological forms: budding yeast, pseudohyphae and hyphae [2][3][4][5]. The morphogenetic transition has been commonly described as a critical trait for survival and virulence in the host, even though the analysis of a wide array of C. albicans knock-out mutants suggests that pathogenesis can be dissociated to some extent from morphological switching [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

A comprehensive functional portrait of two heat shock factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence

Znaidi

Nesseir

Chauvel

et al. 2013

Journal de Mycologie Médicale

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Sfl1p and Sfl2p are two homologous heat shock factor-type transcriptional regulators that antagonistically control morphogenesis in Candida albicans, while being required for full pathogenesis and virulence. To understand how Sfl1p and Sfl2p exert their function, we combined genome-wide location and expression analyses to reveal their transcriptional targets in vivo together with the associated changes of the C. albicans transcriptome. We show that Sfl1p and Sfl2p bind to the promoter of at least 113 common targets through divergent binding motifs and modulate directly the expression of key transcriptional regulators of C. albicans morphogenesis and/or virulence. Surprisingly, we found that Sfl2p additionally binds to the promoter of 75 specific targets, including a high proportion of hyphal-specific genes (HSGs; HWP1, HYR1, ECE1, others), revealing a direct link between Sfl2p and hyphal development. Data mining pointed to a regulatory network in which Sfl1p and Sfl2p act as both transcriptional activators and repressors. Sfl1p directly represses the expression of positive regulators of hyphal growth (BRG1, UME6, TEC1, SFL2), while upregulating both yeast form-associated genes (RME1, RHD1, YWP1) and repressors of morphogenesis (SSN6, NRG1). On the other hand, Sfl2p directly upregulates HSGs and activators of hyphal growth (UME6, TEC1), while downregulating yeast form-associated genes and repressors of morphogenesis (NRG1, RFG1, SFL1). Using genetic interaction analyses, we provide further evidences that Sfl1p and Sfl2p antagonistically control C. albicans morphogenesis through direct modulation of the expression of important regulators of hyphal growth. Bioinformatic analyses suggest that binding of Sfl1p and Sfl2p to their targets occurs with the co-binding of Efg1p and/or Ndt80p. We show, indeed, that Sfl1p and Sfl2p targets are bound by Efg1p and that both Sfl1p and Sfl2p associate in vivo with Efg1p. Taken together, our data suggest that Sfl1p and Sfl2p act as central ''switch on/off'' proteins to coordinate the regulation of C. albicans morphogenesis.

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Growth of Candida albicans hyphae

Cited by 934 publications

References 139 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

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

A comprehensive functional portrait of two heat shock factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence

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