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Bioactive Compounds / Food Microbiology  |  Bioactive compounds and Physiological properties

Microbiol. Biotechnol. Lett. 2020; 48(4): 429-438

https://doi.org/10.48022/mbl.2002.02006

Received: February 13, 2020; Accepted: April 11, 2020

Sclerotiorin: a Novel Azaphilone with Demonstrated Membrane Targeting and DNA Binding Activity against Methicillin-Resistant Staphylococcus aureus

Chakradhar Dasagrandhi1*, Anup Pandith2, 3 and Khalid Imran1

1Krupanidhi Degree College, Varthur (Hobli), Off Sarjapur Road, Carmelaram Post, Bangalore, India-560035, 2Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Vietnam, 3Faculty of Applied Science, Ton Duc Thang University, Ho Chi Minh City, Vietnam

Correspondence to :
Chakradhar Dasagrandhi
dasagrandhichakradhar@gmail.com

The emergence of multi-drug resistant, pathogenic methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health and has created a need for novel functional therapeutic agents. In this study, we evaluated the underlying mechanisms of the anti-MRSA effect of an azaphilone pigment, sclerotiorin (SCL) from Penicillium sclerotiorum. The antimicrobial activity of SCL was evaluated using agar disc diffusion, broth microdilution, time-kill assays and biophysical studies. SCL exhibits selective activity against Gram positive bacteria including MRSA (range, MIC = 128-1028 μg/ml) and exhibited rapid bactericidal action against MRSA with a > 4 log reduction in colony forming units within three hours of administration. Biophysical studies, using fluorescent probes and laser or electron microscopy, demonstrated a SCL dose-dependent alternation in membrane potential (62.6 ± 5.0.4% inhibition) and integrity (> 95 ± 2.3%), and the release of UV260 absorbing materials within 60 min (up to 3.2 fold increase, p < 0.01) of exposure. Further, SCL localized to the cytoplasm and hydrolyzed plasmid DNA. While in vitro checkerboard studies revealed that SCL potentiated the antimicrobial activity of topical antimicrobials such as polymixin, neomycin, and bacitracin (Fractional Inhibitory Concentration Index range, 0.26-0.37). Taken together these results suggest that SCL targets the membrane and DNA of MRSA to facilitate its anti- MRSA antimicrobial effect.

Keywords: Azaphilones, sclerotiorin, antimicrobial agents, MRSA, membrane action, synergy

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