Achyrofuran is an antibacterial agent capable of killing methicillin-resistant vancomycin-intermediate Staphylococcus aureus in the nanomolar range

• Published in: Phytomedicine (Stuttgart) Vol. 20; no. 2; pp. 133 - 138
• Main Authors: Casero, Carina, Estévez-Braun, Ana, Ravelo, Ángel G., Demo, Mirta, Méndez-Álvarez, Sebastián, Machín, Félix
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 15-01-2013; Urban & Fischer Verlag
• Subjects: Achyrocline - chemistry; Achyrocline satureioides; Achyrofuran; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibacterial agents; Antibiotics; Antimicrobial; Antimicrobial activity; Argentina; Care and treatment; Chemical properties; Compositae; Data processing; Dichloromethane; Dose-Response Relationship, Drug; Drug resistance; Drug Resistance, Bacterial - drug effects; Furans - isolation & purification; Furans - pharmacology; Health aspects; Hospitals; Infection; Medicinal plants; Medicine, Botanic; Medicine, Herbal; Methicillin Resistance - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Minimum inhibitory concentration; MRSA; Phytoalexins; Plant Components, Aerial - chemistry; Plant extracts; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Staphylococcus aureus; Staphylococcus aureus infections; Vancomycin Resistance - drug effects; Argentina; Spain; Antimicrobial; Achyrofuran; Phytoalexins; Achyrocline satureioides; Staphylococcus aureus; MRSA
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2012.11.003

Currently, there is a pressing need for novel antibacterial agents against drug-resistant bacteria, especially those which have been common in our communities and hospitals, such as methicillin-resistant Staphylococcus aureus (MRSA). The South American plant Achyrocline satureioides (“Marcela”) has been widely used in traditional medicine for a number of diseases, including infections. Several crude extracts from this plant have shown good antimicrobial activities in vitro. In the search for the active principle(s) that confers these antimicrobial activities, we have processed the dichloromethane extract from the aerial parts of the plant. One of the isolated compounds showed extraordinary antibacterial activities against a set of clinically relevant Gram-positive strains that widely differ in their antibiogram profiles. This compound was identified as achyrofuran on the basis of its spectroscopic and physical data. We determined the MIC to be around 0.1μM (0.07μg/ml) for the reference methicillin-resistant and vancomycin-intermediate S. aureus strain NRS402. Moreover, nanomolar concentrations of achyrofuran killed 106 bacteria within 12h. Based on the presence of the 2,2′-biphenol core, we further studied whether achyrofuran killed bacteria through a mechanism of action similar to that reported for the naturally occurring antibiotic MC21-A. Indeed, we found that achyrofuran was not bacteriolytic by itself although it greatly compromised membrane impermeability as determined by increased SYTOX Green uptake.