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Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies
Authors:Michio Kurosu  Katsuhiko Mitachi  Junshu Yang  Edward V. Pershing  Bruce D. Horowitz  Eric A. Wachter  John W. Lacey  III  Yinduo Ji  Dominic J. Rodrigues
Affiliation:1.Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA;2.Department of Veterinary and Biomedical Sciences, University of Minnesota, 205 VSB, 1971 Commonwealth Avenue, Saint Paul, MN 55108, USA; (J.Y.); (Y.J.);3.Provectus Biopharmaceuticals, Inc., 10025 Investment Drive, Suite 250, Knoxville, TN 37932, USA; (E.V.P.); (B.D.H.); (E.A.W.); (J.W.L.III); (D.J.R.)
Abstract:Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80–95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01–3.13 μg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10−13). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal’s bactericidal activity under dark conditions.
Keywords:rose bengal (RB)   high-purity form of rose bengal (HP-RB)   antibacterial activity   drug-resistant gram-positive pathogens   multidrug-resistant bacteria   methicillin-resistant Staphylococcus aureus   vancomycin resistant Enterococcus faecium   biofilms   whole genome analyses
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