Antimicrobial activity and synergism of ursolic acid 3-O-α-L-arabinopyranoside with oxacillin against methicillin-resistant Staphylococcus aureus

Abstract

The objective of the present study was to investigate the antibacterial activity of a single constituent, ursolic acid 3-O-α-L-arabinopyranoside (URS), isolated from the leaves of Acanthopanax henryi (Oliv.) Harms, alone and in combination with oxacillin (OXA) against methicillin-resistant Staphylococcus aureus (MRSA). A broth microdilution assay was used to determine the minimal inhibitory concentration (MIC). The synergistic effects of URS and OXA were determined using a checkerboard dilution test and time-kill curve assay. The mechanism of action of URS against MRSA was analyzed using a viability assay in the presence of a detergent and an ATPase inhibitor. Morphological changes in the URS-treated MRSA strains were evaluated via transmission electron microscopy (TEM). In addition, the producing penicillin-binding protein 2a (PBP2a) protein level was analyzed using western blotting. The MIC value of URS against MRSA was found to be 6.25 µg/ml and there was a partial synergistic effect between OXA and URS. The time-kill growth curves were suppressed by OXA combined with URS at a sub-inhibitory level. Compared to the optical density at 600 nm (OD600) value of URS alone (0.09 µg/ml), the OD600 values of the suspension in the presence of 0.09 µg/ml URS and 0.00001% Triton X-100 or 250 µg/ml N,N'-dicyclohexylcarbodiimide reduced by 56.6 and 85.9%, respectively. The TEM images of MRSA indicated damage to the cell wall, broken cell membranes and cell lysis following treatment with URS and OXA. Finally, an inhibitory effect on the expression of PBP2a protein was observed when cells were treated with URS and OXA compared with untreated controls. The present study suggested that URS was significantly active against MRSA infections and revealed the potential of URS as an effective natural antibiotic.

Staphylococcus aureus colonisation in patients from a primary regional hospital

“…Another factor that argues against cross-transmission is the large number of different strains discovered ( 28 ). The effect of specific antibiotics on MRSA strains has been previously analysed ( 29 ). It was shown that the resistance level of MRSA in patients who received antibiotic therapy was 2-fold compared to that in those who did not undergo antibiotic treatment ( 30 ).…”

Isolation of Phytochemical Constituents from Hunteria umbellata K. Schum

“…ursolic acid (1) and oleanolic acid (2) have already exhibited antimicrobial properties and its mechanism is established. 21,22 Oleanolic acid has also exhibited anti-tubercular activity. 23 The derivatives of oleanolic acid have been reported for the treatment of pancreatic cancer, 24 and oleanolic acid saponins have shown significant antimicrobial properties, 25 and the combination of oleanolic acid with hypocrellin A has been reported for the treatment of hepatocellular carcinoma diseases, 26 and oleanolic acid derivative SZC014 has exhibited anticancer activity.…”

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“…ursolic acid (1) and oleanolic acid (2) have already exhibited antimicrobial properties and its mechanism is established. 21,22 Oleanolic acid has also exhibited anti-tubercular activity. 23 The derivatives of oleanolic acid have been reported for the treatment of pancreatic cancer, 24 and oleanolic acid saponins have shown significant antimicrobial properties, 25 and the combination of oleanolic acid with hypocrellin A has been reported for the treatment of hepatocellular carcinoma diseases, 26 and oleanolic acid derivative SZC014 has exhibited anticancer activity.…”