Antibacterial Activity and Mode of Action of Lactoquinomycin A from Streptomyces bacillaris
1
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea
2
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2021, 19(1), 7; https://doi.org/10.3390/md19010007
Received: 2 December 2020
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Revised: 19 December 2020
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Accepted: 23 December 2020
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Published: 24 December 2020
This study aims to isolate and identify the structure of antibacterial compounds having potent activity on methicillin-resistant Staphylococcus aureus (MRSA) from marine actinomycetes, and also to identify their mode of action. Lactoquinomycin A (LQM-A) (compound 1) and its derivatives (2–4) were isolated from marine-derived Streptomyces bacillaris strain MBTC38, and their structures were determined using extensive spectroscopic methods. These compounds showed potent antibacterial activities against Gram-positive bacteria, with MIC values of 0.06–4 μg/mL. However, the tested compounds exhibited weak inhibitory activity against Gram-negative bacteria, although they were effective against Salmonella enterica (MIC = 0.03–1 μg/mL). LQM-A exhibited the most significant inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC = 0.25–0.5 μg/mL), with a low incidence of resistance. An in vivo dual-reporter assay designed to distinguish between compounds that inhibit translation and those that induce DNA damage was employed to assess the mode of action of LQM-A. LQM-A-induced DNA damage and did not inhibit protein synthesis. The gel mobility shift assay showed that LQM-A switched plasmid DNA from the supercoiled to relaxed form in a time- and concentration-dependent manner. These data suggest that LQM-A intercalated into double-stranded DNA and damaged DNA repair.
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Keywords:
Streptomyces bacillaris; lactoquinomycins; methicillin-resistant Staphylococcus aureus; dual-reporter system; DNA intercalation
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MDPI and ACS Style
Chung, B.; Kwon, O.-S.; Shin, J.; Oh, K.-B. Antibacterial Activity and Mode of Action of Lactoquinomycin A from Streptomyces bacillaris. Mar. Drugs 2021, 19, 7. https://doi.org/10.3390/md19010007
AMA Style
Chung B, Kwon O-S, Shin J, Oh K-B. Antibacterial Activity and Mode of Action of Lactoquinomycin A from Streptomyces bacillaris. Marine Drugs. 2021; 19(1):7. https://doi.org/10.3390/md19010007
Chicago/Turabian StyleChung, Beomkoo, Oh-Seok Kwon, Jongheon Shin, and Ki-Bong Oh. 2021. "Antibacterial Activity and Mode of Action of Lactoquinomycin A from Streptomyces bacillaris" Marine Drugs 19, no. 1: 7. https://doi.org/10.3390/md19010007
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