Hyphal Morphology and Elongation Alterations in Aspergillus nidulans Provoked by the Diterpene Kaurenoic Acid

Kaurenoic acid (KA), a kaurane-type diterpene extracted from leaves of Mikania hirsutissima, was previously reported as an inhibitor of vascular contractility mainly by blocking extracellular Ca2+ influx. The compound is known for several other biological activities such as antiparasitic, antispasmodic and antibacterial activity. The aim of the present study was to investigate the effect of KA on Aspergillus nidulans. KA (0.3 mM) showed fungistatic activity against A. nidulans with visible hyphal elongation and morphology damage. These effects were reverted by CaCl2 addition showing that KA interferes with intracellular Ca2+ gradient in A. nidulans. This is the first report on the mechanism of action of KA involving calcium levels by altering the elongation of fungi hyphae.

[1]  E. Käfer.  Meiotic and mitotic recombination in Aspergillus and its chromosomal aberrations. , 1977, Advances in Genetics.

[2]  A. M. de Oliveira,et al.  Analysis of the mechanisms underlying the vasorelaxant action of kaurenoic acid in the isolated rat aorta. , 2004, European journal of pharmacology.

[3]  F. D. da Costa,et al.  Antimicrobial Activity of Kaurane Diterpenes against Oral Pathogens , 2008, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[4]  R. Lew,et al.  Calcium gradient dependence of Neurospora crassa hyphal growth. , 2003, Microbiology.

[5]  S. Said,et al.  The Difference in Calcium Levels in Aspergillus nidulans Grown on Glucose or Pectin , 2012 .

[6]  A. M. de Oliveira,et al.  Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility. , 2006, Life sciences.

[7]  J. López-Barneo,et al.  Metabotropic Regulation of RhoA/Rho-Associated Kinase by L-type Ca2+ Channels: New Mechanism for Depolarization-Evoked Mammalian Arterial Contraction , 2011, Circulation research.

[8]  W. Cunha,et al.  Evaluation of ent-Kaurenoic Acid Derivatives for their Anticariogenic Activity , 2011, Natural product communications.

[9]  Hua Wei,et al.  Osmotic stabilizer-coupled suppression of NDR defects is dependent on the calcium-calcineurin signaling cascade in Aspergillus nidulans. , 2011, Cellular signalling.

[10]  A. Pomilio,et al.  ent‐Kaur‐16‐en‐19‐oic acid, a KB cells cytotoxic diterpenoid from Elaeoselinum foetidum , 2002, Phytotherapy research : PTR.

[11]  A. Ram,et al.  Functional characterization of Rho GTPases in Aspergillus niger uncovers conserved and diverged roles of Rho proteins within filamentous fungi , 2011, Molecular microbiology.

[12]  D. G. Lee,et al.  In vitro candidacidal action of Korean red ginseng saponins against Candida albicans. , 2008, Biological & pharmaceutical bulletin.

[13]  E. Chiari,et al.  Synthesis and trypanocidal activity of ent-kaurane glycosides. , 2007, Bioorganic & medicinal chemistry.

[14]  S. Said,et al.  Evidence for carbon source regulated protein kinase A and protein kinase C signaling in the duplication cycle, polarization and septum formation in Aspergillus nidulans. , 2002, Microbiological research.

[15]  E. Ghisalberti.  The biological activity of naturally occurring kaurane diterpenes , 1997 .

[16]  S. Harris,et al.  Regulation of hyphal morphogenesis by cdc42 and rac1 homologues in Aspergillus nidulans , 2007, Molecular microbiology.

[17]  David J. Newman.  Natural Products as Leads to Potential Drugs: An Old Process or the New Hope for Drug Discovery? , 2008 .

[18]  Dionéia C. R. Oliveira,et al.  Kaurene diterpenes and other chemical constituents from Mikania stipulacea (M. Vahl) willd , 2001 .

[19]  H. Chokshi,et al.  Separation of Diterpenoid Alkaloid Mixtures Using Vacuum Liquid Chromatography , 1986 .