Vancomycin resistance reversal in enterococci by flavonoids

Abstract

The development of clinical vancomycin-resistant strains of enterococci (VRE) is a major cause for concern. Here we show that a combination of galangin or 3,7-dihydroxyflavone with vancomycin may be used to sensitize resistant strains of Enterococcus faecalis and Enterococcus faecium to the level of vancomycin-sensitive strains. Minimum inhibitory concentrations (MICs) and viable counts were determined in Iso-sensitest broth using a microtitre method. MICs of vancomycin against 67% of resistant clinical isolates and a type strain of enterococci were lowered from > 250 microg mL(-1) to < 4 microg mL(-1) in the presence of galangin (12.5 microg mL(-1)) or 3,7-dihydroxyflavone (6.25 microg mL(-1)). Viable counts for type culture E. faecalis ATCC 51299 showed the flavonoids alone significantly lowered numbers of colony forming units (CFUs). CFUs were maintained at low levels (< 10(3) CFU mL(-1)) for 24 h by vancomycin/flavone combinations. This combinational action in reversing vancomycin resistance of enterococci highlights novel drug targets and has importance in the design of new therapeutic regimes against resistant pathogens.

Galbanic Acid from Ferula szowitsiana Enhanced the Antibacterial Activity of Penicillin G and Cephalexin against Staphylococcus aureus

“…4,5) In this regard, interest has increased in plant-based natural products to combat infectious diseases. [6][7][8] The natural product reserpine is known to inhibit the multidrug transporter NorA and to enhance the activity of fluoroquinolone antibiotic norfloxacin. 9) In our program's search we have been screening various plants for their ability to decrease bacterial resistance to penicillin G and cephalexin, which are extensively used to treat infections caused by bacteria.…”

Antibacterial activity of phytochemicals isolated from Erythrina zeyheri against vancomycin‐resistant enterococci and their combinations with vancomycin

“…Sato et al (1995b) reported that the combination of 5,7,2′,4′-tetrahydroxy-8-lavandulyl-flavanone (sophoraflavanone G) from Sophora exigua with vancomycin, minocycline, rifampicin or trimethoprim-sulfamethoxazole acts synergistically against the growth of MRSA strains. It was shown by Liu et al (2001) that 67% of clinically isolated VRE strains demonstrated a noticeable reduction in their resistance to vancomycin when combined with galangin (12.5 µg/mL) or 3,7-dihydroxyflavone (6.25 µg/mL), whereas neither flavonoid alone inhibited these strains at 250 µg/mL. In our investigation of the effect of combining of erybraedin A or eryzerin C with vancomycin on the growth of VRE and MRSA strains, FIC indices revealed that all combinations either act synergistically or act additively against both bacterial species, and that eryzerin C had a higher synergistic effect with vancomycin than did erybraedin A with vancomycin.…”

Sophoraflavanone G from Sophora pachycarpa Enhanced the Antibacterial Activity of Gentamycin against Staphylococcus aureus

“…This approach has the advantage of extending the usefulness of antibiotics with known pharmacological, toxicological and treatment properties (Renau et al, 1998;Wright, 2000). In this regard, interest has increased in plant-based natural products to combat infectious diseases (Cowan, 1999;Liu et al, 2001;Oumzil et al, 2002;Mimica-Dukic et al, 2003;Shahverdi et al, 2004). The natural product reserpine is known to inhibit the multidrug transporter NorA and to enhance the activity of the fluoroquinolone antibiotic norfloxacin (Markham and Neyfakh, 1996).…”