Synergistic Effect between Cryptotanshinone and Antibiotics against Clinic Methicillin and Vancomycin‐Resistant Staphylococcus aureus

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 μg/mL; for MSSA 1-2 from 16 to 32 μg/mL and 64 to 128 μg/mL; for VRSA 1-2 from 2 to 4 μg/mL and 4 to 16 μg/mL, respectively. The range of MIC50 and MIC90 of CT was 0.5–8 μg/mL and 4–64 μg/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.

Synergistic Effect between Fucoidan and Antibiotics against Clinic Methicillin-Resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt;

“…In Gram-negative bacteria, the outer membrane acts as a barrier to many environmental substances including antibiotics [32]. Combinations of some herbal materials and different antibiotics might affect the inhibitory effect of these antibiotics [11] [27] [28] [30] [33]. The combination of oxacillin and fucoidan resulted in a reduction in the MICs/MBCs for tested all bacteria, with the MICs/MBCs of 16/32 or 128/256 μg/mL and for oxacillin becoming 2 -128/4 -256 μg/mL and reduced by ≥4-fold in most of tested MRSA, evidencing a synergistic effect as defined by a FICI of ≤0.5 except MRSA 1, 5, 7, 16, and 19 and by a FBCI of ≤0.5 except MRSA 5, 7, 9, 16, and 19 ( Table 2).…”

“…The antimicrobial activities of fucoidan against clinical isolates MRSA 20 and reference strains were determined via the broth dilution method [28]. The minimum inhibitory concentration (MIC) was recorded as the lowest concentration of test samples resulting in the complete inhibition of visible growth.…”

“…The synergistic combinations were investigated in the preliminary checkerboard method performed using the MRSA 1 -20 of clinical isolate strains via MIC and MBC determination [6] [28]. The fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) are the sum of the FICs and FBCs of each of the drugs, which were defined as the MIC and MBC of each drug when used in combination divided by the MIC and MBC of each drug when used alone.…”

Bacteriocins and their position in the next wave of conventional antibiotics

“…Examples of more recent synthetic chemical efforts include high-throughput screening of Page 6 of 40 A c c e p t e d M a n u s c r i p t chemical libraries and targeted structure-guided experiments [23,24]. In addition, there are groups devoted to isolating and screening various natural and naturederived sources.…”

Phytochemical and biological research of Salvia medicinal resources

“…The antibacterial action of cryptotanshinone (CT) may be associated with its action as active oxygen radical generator (Feng et al, 2009); Staphylococcus aureus undergoes an oxygen-limiting state upon exposure to CT. CT and antibiotics had synergistic effect against clinical methicillin-and vancomycin-resistant Staphylococcus aureus (Cha et al, 2014). 7-(2-Oxohexyl)-taxodione, a novel taxodione derivative of S. austriaca, has antimicrobial and antibiofilm properties (Kuźma et al, 2012a).…”