2-Alkyl-4-hydroxyquinolines from a Marine-Derived Streptomyces sp. Inhibit Hyphal Growth Induction in Candida albicans

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.

A comparative study of N‐hydroxylating flavoprotein monooxygenases reveals differences in kinetics and cofactor binding

“…S1) additionally contain several genes encoding enzymes involved in fatty acid biosynthesis and redox enzymes, which may contribute to recruitment of the acyl moiety and/or tailoring of the AQ scaffold. In the light of antibacterial, antifungal and antialgal properties exhibited by members of this compound class [39][40][41][42][43][44], the perspective of discovering new bioactive AQs or derivatives thereof might encourage a more detailed analysis of the BGCs present in, for example, C. nematophagum, H. rubripertinctus or A. aurantiaca. Based on comparative analyses of BGCs and the detection of 2-ABA in C. nematophagum culture supernatants, we assumed its PqsL homolog WP_122547107.1 (termed PqsL Cn ) to be isofunctional to PqsL and HmqL and hence a suitable candidate for comparative analysis.…”

“…S1) additionally contain several genes encoding enzymes involved in fatty acid biosynthesis and redox enzymes, which may contribute to recruitment of the acyl moiety and/or tailoring of the AQ scaffold. In the light of antibacterial, antifungal and antialgal properties exhibited by members of this compound class [39–44], the perspective of discovering new bioactive AQs or derivatives thereof might encourage a more detailed analysis of the BGCs present in, for example, C . nematophagum , H .…”

Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus

“…This includes 2-alkyl-4-hydroxyquinoline antibiotics and antifungals produced by Streptomyces sp. strain MBTG13 isolated from sediments of Jeju Island, South Korea (Kim et al, 2019), polycyclic polyether compounds, terrosamycins A and B, produced by Streptomyces sp. RKND004 isolated from sediments of Prince Edward Island, Canada (Sproule et al, 2019), and oxazole-triene compound, inthomycin B, produced by Streptomyces sp.…”

A Perspective on Enzyme Inhibitors from Marine Organisms

“…Further, it was described to inhibit the growth of several Gram-positive bacteria, including Mycobacterium species [6]. Also, 2-alkyl-4-hydroxyquinoline derivatives from Streptomyces have bioactive capacities, as some can regulate hyphal growth of Candida [7]. These are only a few examples of natural products obtained from marine sources, however, they demonstrate the spectrum of applicability to some extent.…”