Mammea B/BA Isolated From the Seeds of Mammea americana L. (Calophyllaceae) is a Potent Inhibitor of Methicillin-Resistant Staphylococcus aureus

Abstract

Staphylococcus aureus remains a pathogen of high concern in public health programs worldwide due to antibiotic resistance and emergence of highly virulent strains. Many phytochemicals have demonstrated activity against S. aureus and other Gram-positive bacteria, but the minimum inhibitory concentration (MIC) values comparable to commonly used antibiotics are needed. In the present study, bio-guided fractionation of the ethanol extract of seeds of Mammea americana L. (Calophyllaceae) throughout the antibacterial activity, against S. aureus strains that are sensitive and resistant to methicillin, led to the isolation of four coumarins identified as mammea B/BA, mammea B/BC, mammea A/AA cyclo D and mammea A/AA cyclo F, and a mixture of mammea B/BA cyclo F plus mammea B/BD cyclo F. The extract inhibited the growth of S. aureus with MIC values of 2–4 μg/ml and Mammea B/BA (MaBBA) presented MIC values in a range between 0.5 and 1.0 μg/ml in six methicillin-sensitive strains and eight methicillin-resistant strains evaluated. We consider MaBBA the most potent of all mammea coumarins reported to date, according to the literature review carried out at the time of writing of this article. Toxicity assessment in vivo against the nematode Caenorhabditis elegans and in vitro against human fibroblasts of the extract and the compound MaBBA indicated that both had low toxicity.

Antibacterial Effect of Ethanolic Extracts of Dodonaea viscosa L. Jacq. and Mammea americana L. against Staphylococci Isolated from Skin Lesions

“…Manjulatha [ 36 ] mentioned an MBC ranging from 125 μ g/mL to 500 μ g/mL using the ethanolic seed extracts of M. americana against Streptococcus mutans ATCC 25175 (gram-positive bacteria). Similarly, Pajaro-Gonzalez et al [ 12 ] report MBC higher than 64 μ g/mL (>64 μ g/mL) establishing in their investigation a bacteriostatic effect of the extract. Interestingly, the ethanolic extract of the aerial part of M. americana presented greater activity against S. epidermidis strains (91 μ g/mL to 540 μ g/mL) followed by the MBC of isolated and ATCC strains of S. aureus (625 μ g/mL and 650 μ g/mL, respectively) and finally by S. saprophyticus (1750 μ g/mL).…”

“…Regarding this, a significant number of reports highlight the biological activities of M. americana , such as potential source of natural antioxidants, antimicrobial and even for the treatment of skin diseases [ 10 , 11 ]). Furthermore, a recent study by Pajaro-Gonzalez et al [ 12 ] reported antibacterial activity at low concentrations of the ethanol extract of the seeds of M. americana against S. aureus (ATCC and clinical) strains that are sensitive and resistant to methicillin. Regarding D. viscosa , several reports of its antibacterial activity can be found in the literature.…”

Plant antibacterials: The challenges and opportunities

“…Schneid 0.5–8 μg/mL against Gram-positive bacteria, 2 μg/mL E . coli, < 1 μg/mL against M. smegmatis [ 69 , 70 ] 4 Mammea B/BA Mammea americana L. 0.5–1 μg/mL against methicillin-sensitive and methicillin-resistant S. aureus strains [ 74 , 77 ] 5 Cannabinoids (e.g., cannabidiol, cannabigerol) Cannabis sativa L. 1–4 μg/mL against MRSA , multi-drug resistant Streptococcus pneumoniae, Enterococcus faecalis , and Clostridioides difficile [ 85 , 86 ] 6 27- epi -Scutianine N Scutia buxifolia Reissek 1.56 μg/mL against Enterobater aerogenes [ 126 ] 7 Berberine Hydrastis canadensis. L , Coptis chinensis Franch.…”

“…Coumarins in the genus Mammea have been chemically categorized into 4-(phenyl)coumarins, 4-(alkyl)coumarins and 4-(1-acetoxypropyl)coumarins [ 76 ]; Mammea B/BA is a 4-(alkyl)coumarin. In a recent bio-guided fractionation study, Pájaro-González et al (2022) reported the isolation of mamey coumarin-type Mammea B/BA from the ethanol seed extract of Mammea americana (mamey), and its anti- Stapylococcal activity [ 77 ].…”

“…Mammea B/BA showed significant activity against strains of methicillin-sensitive S. aureus ATCC 29213 (MIC, 1 μg/mL); and methicillin-resistant S. aureus ATCC 33591 (MIC, 0.5 μg/mL), ATCC 43300 (MIC, 0.5 μg/mL), and USA300-0114 (MIC, 1 μg/mL). The antibacterial activity of Mammea B/BA (MIC 0.5–1 μg/mL) was comparable to that of vancomycin (MIC, 1 μg/mL) and gentamicin (MIC, 0.25–>8 μg/mL) [ 77 ]. Pájaro-González et al (2022) proposed that the antibacterial activity of Mammea B/BA is due to the presence of a prenyl group at its position C6 and acyl group at position C8.…”