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Inhibitory and Resistance-Modifying Potential of Plant-Based Alkaloids Against Methicillin-Resistant Staphylococcus aureus (MRSA)

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Abstract

Increased prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat to the health sector worldwide due to their virulence, limited therapeutic options and their distribution in both hospital and community settings. Discovery and development of new anti-MRSA agents as alternatives to the very few antibiotics left in the armamentarium are, thus, urgently required. Recently, an efflux mechanism in MRSA has been identified as one of the main contributors of resistance towards various structurally unrelated antibiotics. The potential of reserpine (a phytoalkaloid) as efflux pump inhibitor (EPI) against various microbes remains limited as the concentration needed for inhibition is toxic to humans. This study therefore aimed to evaluate 13 alkaloid compounds as potential inhibitory agents and/or potential EPIs against a panel of three MRSA isolates which not only differ in their susceptibility to vancomycin (amongst the last drugs available to treat serious MRSA infection), but also exhibited active efflux activity. Results indicated berberine’s moderate inhibitiory activity against two MRSA isolates scoring a minimum inhibitory concentration (MIC) value of 125 μg/ml. Notable efflux inhibitory activity (ranging from two- to eightfold Ethidium Bromide MIC reduction) meanwhile was detected from quinine, piperine and harmaline using reserpine as the positive control. Findings from this study support the opinion that a vast number of potential phytocompounds with pharmacological potential await discovery. Therapeutic application of these compounds, however, warrants further investigation to ascertain their pharmacodynamics and safety aspects.

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Acknowledgments

The authors acknowledge the funding support provided by the Forest Research Institute Malaysia (TGP - 40-300-40-3007), and Ministry of Science, Technology and Innovation, Malaysia (eIRPA - 30-300-40-3010), and thank Mrs. Hannan Abdul Wahab and Mr. Izanudin Zakaria for their technical assistance.

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Authors and Affiliations

  1. Antimicrobial Laboratory, Medicinal Plants Programme, Forest Biotechnology Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia

    Mastura Mohtar, Saiful Azmi Johari & Mazurah Mohamed Isa

  2. Chemistry Unit, Medicinal Plants Programme, Forest Biotechnology Division, Forest Research Institute Malaysia, Kepong, Selangor, Malaysia

    Abdul Rashid Li

  3. Department of Microbiology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

    Shuhaimi Mustafa

  4. Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

    Abdul Manaf Ali

  5. Department of Biomedicine, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Dayang Fredalina Basri

Authors
  1. Mastura Mohtar
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  2. Saiful Azmi Johari
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  3. Abdul Rashid Li
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  4. Mazurah Mohamed Isa
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  5. Shuhaimi Mustafa
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  6. Abdul Manaf Ali
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  7. Dayang Fredalina Basri
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Corresponding author

Correspondence to Mastura Mohtar.

Additional information

This study was supported by the FRIM’s Young Scientist Grant No. 40-300-40-3007 and the Intensified Research in Priority Areas (IRPA) Grant No. 30-300-40-3010 from the Ministry of Science, Technology and Innovation, Malaysia.

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Mohtar, M., Johari, S.A., Li, A.R. et al. Inhibitory and Resistance-Modifying Potential of Plant-Based Alkaloids Against Methicillin-Resistant Staphylococcus aureus (MRSA). Curr Microbiol 59, 181–186 (2009). https://doi.org/10.1007/s00284-009-9416-9

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  • DOI: https://doi.org/10.1007/s00284-009-9416-9

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