Pterostilbene Enhanced Anti-Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Activity of Oxacillin

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a deadly pathogen that initially was limited to hospital and healthcare facilities but has gradually became a growing problem in healthy children and adults. Pterostilbene belongs to the phenylpropanoid phytoalexin which is involved in plant response to various pathogen and herbivores attack. The aim of this study is to evaluate the anti-MRSA action of pterostilbene in combination with selected antibiotics; vancomycin, linezolid and oxacillin against ATCC 43300 and ATCC 33591. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and fractional inhibitory concentration (FIC) index values were determined. Microbroth dilution technique and microdilution checkerboard (MDC) assay were employed. The MIC and MBC of pterostilbene against ATCC 33591 was 31.25 and 62.50 µg mL −1 , respectively. While for ATCC 43300, the MBC value was also twice (62.50 µg mL −1 ) its MIC value of 31.25 µg mL −1 . This indicated that pterostilbene was bacteriostatic against both MRSA strains. Our MIC/MBC study also showed that linezolid exhibited bacteriostatic action but, oxacillin and vancomycin were bactericidal. MDC study showed that pterostilbene-oxacillin combination exhibited lowest FIC value (0.56) against both MRSA strains which indicated partial synergistic interaction. On the other hand, pterostilbene was additive (FIC 1.00) in combination with vancomycin whereas pterostilbene-linezolid combination displayed indifference effect with FIC of 1.25 against both MRSA strains. Pterostilbene in combination with oxacillin partially enhanced anti-MRSA activity with twofold reduction in MIC of oxacillin by acting at different site at the bacterial cell wall from that of oxacillin but more specific to the site of action of vancomycin.

Pterostilbene Reduced Post-Antibiotic Effect Time of Linezolid against Methicillin-Resistant Staphylococcus aureus

“…According to Sopirala et al [32] if the MIC of an antibiotic changed within a one-fold dilution, the result was considered as insignificant but because the decreased in the MIC of linezolid in this study was four-fold, the interaction could not possibly be indifference. However, the current FIC data was supported by our previous literature [23] that pterostilbene lacked interaction with linezolid despite the change in the MIC value of linezolid against both MRSA strains.…”

“…Pterostilbene was unique in that it showed lasting suppression of bacterial regrowth, but when employed with linezolid, the combination effect reduced its PAE. Based on the data in this study, we can postulate that pterostilbene could possibly have the same mechanism of action as that of linezolid as proposed in our previous finding [23] that pterostilbene could target the cell wall different from where oxacillin acts. Further studies to confirm that pterostilbene targets the bacterial protein different from the penicillin-binding protein where oxacillin acts are clearly needed to validate this hypothesis.…”

“…A high content of these phenylpropanoid compounds, notably resveratrol and its analogue pterostilbene, identified in Vitis vinifera leaves [15] , heartwood of sandalwood Pterocarpus marsupium [16] and in some species of Vaccinium berries [17] are known to have diverse pharmacological activities [18] . Pterostilbene possesses potent antioxidant activity [19] , anticancer property [20] , anti-antiinflammatory [21] , antifungal [22] and to date, possess antibacterial activity against MRSA [23] .…”

Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria

“…In comparison with gentamicin used as broad spectrum therapy against Gram-positive and Gram-negative infections, pterostilbene still showed 16 times lower antimicrobial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli O157 and four times less inhibitory potency against Pseudomonas aeruginosa ATCC 15442. The same phenomenon was seen in the anti-MRSA effect of pterostilbene whereby both MRSA ATCC and clinical strains are less susceptible to pterostilbene compared to standard antibiotics [ 25 ]. On the other hand, the killing kinetics of Pseudomonas aeruginosa ATCC 15442 demonstrated bacteriostatic activity with less than 3 log 10 CFU/mL reductions in colony count at 24 h compared with the starting inoculum.…”

The relationship between structure and in vitro antistaphylococcal effect of plant-derived stilbenes

“…In previous studies, antimicrobial effect of model stilbene resveratrol and its related structures (e.g., piceatannol, pterostilbene, trans-piceid, and trans-ε-viniferin) has been reported against various food and human pathogenic microorganisms, such as Acetobacter aceti, Acetobacter oeni, Bacillus cereus, Bacillus subtilis, Dekkera bruxellensis, Escherichia coli, Listeria innocua, Listeria monocytogenes, Pseudomonas fluorescens, Pseudomonas aeruginosa, Streptococcus spp., Zygosaccharomyces bailii, and Zygosaccharomyces rouxii [11][12][13][14][15]. The in vitro growth-inhibitory effect of (E)-3-hydroxy-5-methoxystilbene, oxyresveratrol, pterostilbene, and resveratrol has also previously been described against S. aureus and Staphylococcus epidermidis [15][16][17][18].…”