Identification of New Antifungal Agents Targeting Chitin Synthesis by a Chemical-Genetic Method

Li, Yan; Sun, Hongmin; Zhu, Xiaofan; Bian, Cong; Wang, Yanchang; Si, Shuyi

doi:10.3390/molecules24173155

Cited by 17 publications

(10 citation statements)

References 40 publications

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“…It is nacetylglucosamine connected by β-(1,4). Chitin synthase is a key enzyme for biosynthesis of chitin (Li et al, 2019). The 1,3-β -glucan synthase, also known as 1,3-β -d-glucan -UDP glucosyltransferase, catalyzes the polymerization and elongation of glucose chains, thus forming cellulose (Aimanianda et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of the Erythritol High-Yielding Mutant Strain Yarrowia lipolytica Y44

Ren¹,

Ban²,

Huang³

et al. 2021

American Journal of Biochemistry and Biotechnology

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RNA-seq technique was used to analyze the transcriptomics ofYarrowia lipolytica control strain Po1g, an erythritol-producing natural isolate Yarrowia lipolytica Y 22 and an erythritol high-yielding mutant strain Y44 derived from Y 22. Functional annotation of genes and classification of metabolic pathways were carried out to identify Differentially Expressed Genes (DEGs). These DEGs were classified into related metabolic pathways to explain the molecular mechanism of high yield of erythritol production. The results showed that the upregulated genes in erythritol-producing natural isolate Y 22 and erythritol-producing mutant strain Y 44 were mainly involved in pentose phosphate pathway, Tricarboxylic Acid Cycle (TCA) and malic acid cycle. The downregulated genes were mainly involved in amino acid synthesis and oxycarboxylic acid metabolism. The synergistic regulation of the above metabolic pathways can increase the input and reduce the output of erythrose-4-P (E-4-P), which is the precursor of erythritol, promoting erythritol production. In addition, compared with the natural isolate Y 22, the genes related to cell wall synthesis were down-regulated and the expression of transmembrane transporter protein was up-regulated in high-yield mutant strain Y 44. In this way, the permeability of yeast cells is enhanced and the synthesized erythritol can be quickly transported to the outside of the cell, which reduces the decomposition of erythritol and further promotes its yield.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of the Erythritol High-Yielding Mutant Strain Yarrowia lipolytica Y44

Ren¹,

Ban²,

Huang³

et al. 2021

American Journal of Biochemistry and Biotechnology

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“…Chitin content in the cytoderm of C. albicans was assessed as previously described [28]. After staining with calcium fluorescent white (CFW) (GenMed Scientifics, Wilmington, DE, USA), BH-treated fungal cells were observed using a CLSM (excitation wavelength: 405 nm; LEICA TCS SP8 SR, Wetzlar, Germany), and a microplate reader was used to detect the fluorescent intensities of cells (excitation wavelength: 355 nm; emission wavelength: 440 nm).…”

Section: Methodsmentioning

confidence: 99%

Antifungal activity and potential mechanism of berberine hydrochloride against fluconazole-resistant Candida albicans

Huang

Zheng

Yong

et al. 2022

Journal of Medical Microbiology

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Introduction. The emergence of resistance to fluconazole in Candida albicans has made the clinical treatment of this microbe difficult. A potential strategy to address this problem involves diminishing fungal resistance to antimicrobial drugs. Hypothesis. Berberine hydrochloride (BH), the primary active ingredient of the traditional Chinese medicine (TCM) Coptis, inhibits the growth of fluconazole-resistant C. albicans through its action on the high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway. Aim. To examine the effect of BH on the HOG-MAPK pathway to assess the potential molecular mechanism by which BH inhibits fluconazole-resistant C. albicans. Methodology. The minimum inhibitory concentration (MIC) of BH to fluconazole-resistant C. albicans was measured using the broth microdilution approach to determine the concentration of effective drug intervention. Changes in physiological functions regulated by the HOG-MAPK pathway in response to BH treatment were measured, as well as the expression of central signalling pathway genes and key downstream factors by qRT-PCR and Western blotting, respectively. Results. BH inhibited fluconazole-resistant C. albicans and the sensitivity to fluconazole increased after BH treatment. At a concentration of 256 and 64 μg ml−1 BH may affect key downstream factors that regulate several physiological functions of C. albicans by upregulating the core genes expression of SLN1, SSK2, HOG1, and PBS2 in the HOG-MAPK pathway. Upregulation of GPD1, the key gene for glycerol synthesis, increased cell osmotic pressure. BH treatment increased the accumulation of reactive oxygen species by upregulating the expression of the key respiratory metabolism gene ATP11 and downregulating the expression of the superoxide dismutase gene SOD2. Furthermore, downregulation of mycelial-specific HWP1 hindered the morphological transformation of C. albicans and inhibition of the chitin synthase gene CHS3 and the β-(1,3) glucan synthase gene GSC1 impaired cytoderm integrity. Conclusion. BH affects multiple target genes in diminishing the resistance of C. albicans strains to fluconazole. This effect may be related to the action of BH on the HOG-MAPK pathway.

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“…A chemical-genetic method is an approach used to isolate (screen) antifungal agents that target chitin synthesis in fungal cells by impairing chitin synthesis ( Li et al, 2019 ). Two benzothiazoles (IMB-D10 and IMB-F4) ( Fig.…”

Section: Antifungal Treatment Strategiesmentioning

confidence: 99%

Prospects for anti-Candida therapy through targeting the cell wall: A mini-review

2021

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The impact of fungal infections on humans is a serious public health issue that has received much less attention than bacterial infection and treatment, despite ever-increasing incidence exacerbated by an increased incidence of immunocompromised individuals in the population. Candida species, in particular, cause some of the most prevalent hospital-related fungal infections. Fungal infections are also detrimental to the well-being of grazing livestock, with milk production in dairy cows, and body and coat condition adversely affected by fungal infections. Fungal cell walls are essential for viability, morphogenesis and pathogenesis: numerous anti-fungal drugs rely on targeting either the cell wall or cell membrane, but the pipeline of available bioactives is limited. There is a clear and unmet need to identify novel targets and develop new classes of anti-fungal agents. This mini review focuses on fungal cell wall structure, composition and biosynthesis in Candida spp., including C. auris . In addition, an overview of current advances in the development of cell wall targeted therapies is considered.

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Identification of New Antifungal Agents Targeting Chitin Synthesis by a Chemical-Genetic Method

Cited by 17 publications

References 40 publications

Transcriptomic Analysis of the Erythritol High-Yielding Mutant Strain Yarrowia lipolytica Y44

Transcriptomic Analysis of the Erythritol High-Yielding Mutant Strain Yarrowia lipolytica Y44

Antifungal activity and potential mechanism of berberine hydrochloride against fluconazole-resistant Candida albicans

Prospects for anti-Candida therapy through targeting the cell wall: A mini-review

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