Abstract
Four 2-alkyl-4-hydroxyquinoline derivatives (1–4) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC50 value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans.
Highlights
Candida albicans is an important human fungal pathogen that can reversibly transition between two distinct morphological forms: yeast and filamentous hypha [1,2]
MBLG13 led to the isolation of 2-alkyl-4-hydroxyquinoline derivatives (1–4)
Compound 1 was earlier isolated from Pseudomonas aeruginosa and had antibacterial activity against Gram-positive bacteria [14]
Summary
Candida albicans is an important human fungal pathogen that can reversibly transition between two distinct morphological forms: yeast and filamentous hypha [1,2]. The morphological transition ability of the organism contributes to its virulence [3], and hyphal development is closely associated with the dissemination of, and tissue invasion by, C. albicans. C. albicans is triggered by various in vitro environmental signals such as neutral pH, nutrient-poor media, high temperatures, a high ratio of CO2 , and serum exposure [4]. In addition to environmental signals, the morphological transition of C. albicans is controlled by a complex network of signaling pathways, including the Cph1-mediated MAPK pathway and the Efg1-mediated cAMP pathway. Ras likely acts upstream of both pathways as an important regulator of hyphal development [2].
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