Publication:
CINNAMOMUM, ITS ANTIBACTERIAL EFFECTS AND CINNAMOMUM IMPRESSICOSTATUM, IDENTIFICATION OF BIOACTIVE CONSTITUENTS AND POSSIBLE MECHANISMS OF ACTION AGAINST METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS

Date
2014-03
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International Medical University
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Abstract
The emergence of Methicillin Resistant Staphylococcus aureus (MRSA) which is resistant to many available antibacterial agents, especially the β-lactam antibiotics, has become a major threat to the health sector worldwide, giving impetus to the search for novel antibacterial agents efficacious against this bacterium. Four (4) Cinnamomum species i.e. C.iners, C.altissimum, C.impressicostatum and C. porrectum were investigated against a range of multidrug resistant bacteria, including Methicillin Resistant Staphylococcus aureus, our main subject of interest, for potential antibacterial activity and elucidation of their modes and mechanisms of action. Characterisations of their bioactive fractions were performed using bioassay guided isolation techniques. C.impressiscostatum stem-bark extract recorded the highest zone of inhibition and lowest minimum inhibitory concentration against MRSA. The presence of salt enhanced the killing efficiency of the plant extract against MRSA. Cellular materials leaked from MRSA after treatment with the plant extract and this was concomitant with marked cell wall damage, as observed using scanning electron microscopy (SEM). A total of 136 genes were found to be differentially regulated by C. impressicostatum stem-bark extract. Amongst these, 73 genes were upregulated and 63 genes were downregulated. The MRSA genes that fluctuated in expression when treated with the plant extract involved various pathways, such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, nucleotide metabolism, membrane transport, metabolism of cofactors and vitamins, metabolism of terpenoids and polyketides, biosynthesis of secondary metabolites, energy metabolism, folding, sorting and degradation, glycan metabolism, pathways in pathogenesis, replication and repair, signal transduction, transcription, translation, translational ribosomal structure and biogenesis and xenobiotic degradation and metabolism. The possible mechanisms underlying the killing action of C.impressicostatum active fraction of water extract against MRSA are via inhibition of biofilm formation, inhibition of nucleotide metabolism as well as DNA replication and repair, downregulation of the mismatch repair mechanism, thereby enabling maintenance of deleterious and lethal mutations, ultimately causing cell death, induction of increased cellular vulnerability to the effects of reactive oxygen and nitrogen species, inhibition of essential lipid biosynthesis required for cellular structure and metabolism as well as the induction of apoptosis.
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Cinnamomum, Anti-Bacterial Agents, Methicillin-Resistant Staphylococcus aureus, Drug Resistance, Multiple, Bacterial
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