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, 2014, 450572

Synergistic Effect Between Cryptotanshinone and Antibiotics Against Clinic Methicillin and Vancomycin-Resistant Staphylococcus Aureus

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Synergistic Effect Between Cryptotanshinone and Antibiotics Against Clinic Methicillin and Vancomycin-Resistant Staphylococcus Aureus

Jeong-Dan Cha et al. Evid Based Complement Alternat Med.

Abstract

Cryptotanshinone (CT), a major tanshinone of medicinal plant Salvia miltiorrhiza Bunge, demonstrated strong antibacterial activity against clinic isolated methicillin and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) in this experiment. The CT was determined against clinic isolated MRSA 1-16 with MIC and MBC values ranging from 4 to 32 and 8 to 128 μ g/mL; for MSSA 1-2 from 16 to 32 μ g/mL and 64 to 128 μ g/mL; for VRSA 1-2 from 2 to 4 μ g/mL and 4 to 16 μ g/mL, respectively. The range of MIC50 and MIC90 of CT was 0.5-8 μ g/mL and 4-64 μ g/mL, respectively. The combination effects of CT with antibiotics were synergistic (FIC index <0.5) against most of tested clinic isolated MRSA, MSSA, and VRSA except additive, MRSA 4 and 16 in oxacillin, MRSA 6, 12, and 15 in ampicillin, and MRSA 6, 11, and 15 in vancomycin (FIC index < 0.75-1.0). Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after 2-6 h of treatment with the 1/2 MIC of CT, regardless of whether it was administered alone or with ampicillin, oxacillin, or vancomycin. The results suggest that CT could be employed as a natural antibacterial agent against multidrug-resistant pathogens infection.

Figures

Figure 1
Figure 1
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with MIC50 of AMP or OXA, and VAN against VRSA 1 isolates and reference stains, MSSA ATCC 25923 and MRSA ATCC 33591. Bacteria were incubated with MIC of CT (●), AMP, OXA, and VAN, and 1/2 MIC of CT + 1/2 MIC of AMP (○), 1/2 MIC of CT + 1/2 MIC of OXA (), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 2
Figure 2
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against VRSA 2, MSSA 1, and MSSA 2 isolates. Bacteria were incubated with MIC of CT (●), AMP, OXA, and VAN, and 1/2 MIC of CT + 1/2 MIC of AMP (○), 1/2 MIC of CT + 1/2 MIC of OXA (), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 3
Figure 3
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against MRSA 1, 2, and 3 isolates. Bacteria were incubated with MIC of CT (●), AMP, OXA, and VAN, and 1/2 MIC of CT + 1/2 MIC of AMP (○), 1/2 MIC of CT + 1/2 MIC of OXA (), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 4
Figure 4
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against MRSA 4, 5, and 6 isolates. Bacteria were incubated with MIC of CT (●), AMP (○), OXA (), and VAN (), and 1/2 MIC of CT + 1/2 MIC of AMP (●), 1/2 MIC of CT + 1/2 MIC of OXA (○), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 5
Figure 5
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against MRSA 7, 8, and 9 isolates. Bacteria were incubated with MIC of CT (●), AMP (○), OXA (), and VAN (), and 1/2 MIC of CT + 1/2 MIC of AMP (●), 1/2 MIC of CT + 1/2 MIC of OXA (○), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 6
Figure 6
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against MRSA 10, 11, and 12 isolates. Bacteria were incubated with MIC of CT (●), AMP (○), OXA (), and VAN (), and 1/2 MIC of CT + 1/2 MIC of AMP (●), 1/2 MIC of CT + 1/2 MIC of OXA (○), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 7
Figure 7
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against MRSA 13, 14, and 15 isolates. Bacteria were incubated with MIC of CT (●), AMP (○), OXA (), and VAN (), and 1/2 MIC of CT + 1/2 MIC of AMP (●), 1/2 MIC of CT + 1/2 MIC of OXA (○), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.
Figure 8
Figure 8
Time-kill curves of MIC or 1/2 MIC of cryptotanshinone (CT), ampicillin (AMP), oxacillin (OXA), and vancomycin (VAN) alone and its combination with 1/2 MIC of AMP or OXA, and VAN against MRSA 16 isolate. Bacteria were incubated with MIC of CT (●), AMP (○), OXA (), and VAN (), and 1/2 MIC of CT + 1/2 MIC of AMP (●), 1/2 MIC of CT + 1/2 MIC of OXA (○), and 1/2 MIC of CT + 1/2 MIC of VAN () over time. CFU: colony-forming units.

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