Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans

Lv, Quanzhen; Yan, Lan; Feng, Jian; Qiu, Lijuan; Cui, Wen; Qin, Yanghua; Jiang, Yuanying

doi:10.1128/spectrum.03209-22

Cited by 4 publications

(13 citation statements)

References 44 publications

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“…The formation of hyphae in C. albicans is closely linked to its pathogenicity, which enables tissue invasion and drug resistance. , Thus, we investigated the effect of compound 7 , which was selected as a representative of the isolated sphingolipids because of its significant activity and high production, on hyphal formation. As shown in Figure , hyphal lengths decreased with increasing concentrations of compound 7 , and when C.…”

Section: Resultsmentioning

confidence: 99%

“…To elucidate the antifungal mechanisms of the discovered sphingolipids, transcriptome analysis was employed . The expression levels of genes in C.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, the cell concentration was adjusted to 3 × 10 5 cells/mL using RPMI 1640 medium before treatment with 1 × MIC, 2 × MIC or 5 × MIC of compound 7 , as well as methanol (control). After being incubated at 37 °C and 150 rpm for 5 h, the cells were observed using a microscope …”

Section: Methodsmentioning

confidence: 99%

“…To elucidate the antifungal mechanisms of the discovered sphingolipids, transcriptome analysis was employed. 28 The expression levels of genes in C. albicans cells treated with compound 7, as a representative of sphingolipids, or methanol, as a negative control, were assessed. Overall, a total of 341 genes were downregulated, and 72 genes were upregulated (|log 2 FC| ≥ 1 and FDR ≤ 0.05) in the cells treated with compound 7.…”

Section: Evaluation Of Antimicrobialmentioning

confidence: 99%

“…After being incubated at 37 °C and 150 rpm for 5 h, the cells were observed using a microscope. 28 Table 1. 1 H (500 MHz) and 13 The NMR data of compounds 2 and 3 were measured using DMSOd 6 and CD 3 OD, respectively.…”

Section: ■ Introductionmentioning

confidence: 99%

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Discovery of New Antimicrobial Metabolites in the Coculture of Medicinal Mushrooms

Ji,

Tan,

Shang

et al. 2024

J. Agric. Food Chem.

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Bioactivity screening revealed that the antifungal activities of EtOAc extracts from coculture broths of Trametes versicolor SY630 with either Vanderbylia robiniophila SY341 or Ganoderma gibbosum SY1001 were significantly improved compared to that of monocultures. Activity-guided isolation led to the discovery of five aromatic compounds (1−5) from the coculture broth of T. versicolor SY630 and V. robiniophila SY341 and two sphingolipids (6 and 7) from the coculture broth of T. versicolor SY630 and G. gibbosum SY1001. Tramevandins A−C (1−3) and 17-ene-1-deoxyPS ( 6) are new compounds, while 1-deoxyPS ( 7) is a new natural product. Notably, compound 2 represents a novel scaffold, wherein the highly modified p-terphenyl bears a benzyl substituent. The absolute configurations of those new compounds were elucidated by X-ray diffraction, ECD calculations, and analysis of physicochemical constants. Compounds 1, 2, and 5−7 exhibited different degrees of antimicrobial activity, and the antifungal activities of compounds 6 and 7 against Candida albicans and Cryptococcus neoformans are comparable to those of fluconazole, nystatin, and sphingosine, respectively. Transcriptome analysis, propidium iodide staining, ergosterol quantification, and feeding assays showed that the isolated sphingolipids can extensively downregulate the late biosynthetic pathway of ergosterol in C. albicans, representing a promising mechanism to combat antibiotic-resistant fungi.

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Section: Resultsmentioning

confidence: 99%

“…To elucidate the antifungal mechanisms of the discovered sphingolipids, transcriptome analysis was employed . The expression levels of genes in C.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Evaluation Of Antimicrobialmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Discovery of New Antimicrobial Metabolites in the Coculture of Medicinal Mushrooms

Ji,

Tan,

Shang

et al. 2024

J. Agric. Food Chem.

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Biocontrol potential of Burkholderia gladioli STPT16 on postharvest decay of litchi fruit caused by Peronophythora litchii and Colletotrichum fructicola

Xu,

Niu,

Gao

et al. 2025

Food Control

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Discovery of Antifungal Norsesquiterpenoids from a Soil-Derived Streptomyces microflavus: Targeting Biofilm Formation and Synergistic Combination with Amphotericin B against Yeast-like Fungi

Cao,

Tan,

Zhang

et al. 2024

J. Agric. Food Chem.

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Thirty-five norsesquiterpenoids were isolated from the fermentation broth of Streptomyces microflavus from the forest soil of Ailaoshan in China. The structures of new compounds (1–5, 10–26) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra, as well as Mosher’s reagent derivatives method. Norsesquiterpenoids showed different levels of antifungal activity with MIC80 values ranging from 25 to 200 μg/mL against Candida albicans, Candida parapsilosis, and Cryptococcus neoformans. The combining isolated norsesquiterpenoids with amphotericin B resulted in a synergistic interaction against test yeast-like fungi with a fractional inhibitory concentration index < 0.5. Compound 33 significantly inhibited biofilm formation and destroyed the preformed biofilm of fungi. Moreover, 33 downregulated the expression of adhesion-related genes HWP1, ALS1, ALS3, ECE1, EAP1, and BCR1 to inhibit the adhesion of C. albicans. Findings from the current study highlight the potential usage of norsesquiterpenoids from soil-derived Streptomyces for antifungal leads discovery.

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Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans

Cited by 4 publications

References 44 publications

Discovery of New Antimicrobial Metabolites in the Coculture of Medicinal Mushrooms

Discovery of New Antimicrobial Metabolites in the Coculture of Medicinal Mushrooms

Biocontrol potential of Burkholderia gladioli STPT16 on postharvest decay of litchi fruit caused by Peronophythora litchii and Colletotrichum fructicola

Discovery of Antifungal Norsesquiterpenoids from a Soil-Derived Streptomyces microflavus: Targeting Biofilm Formation and Synergistic Combination with Amphotericin B against Yeast-like Fungi

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