Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies

Michio Kurosu; Katsuhiko Mitachi; Junshu Yang; Edward V. Pershing; Bruce D. Horowitz; Eric A. Wachter; John W. Lacey; Yinduo Ji; Dominic J. Rodrigues

doi:10.3390/molecules27010322

Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies

Michio Kurosu, Katsuhiko Mitachi, Junshu Yang, Edward V. Pershing, Bruce D. Horowitz, Eric A. Wachter, John W. Lacey, Yinduo Ji, Dominic J. Rodrigues

Veterinary and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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 multidrugresistant (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.

Original language	English (US)
Article number	322
Journal	Molecules
Volume	27
Issue number	1
DOIs	https://doi.org/10.3390/molecules27010322
State	Published - Jan 1 2022

Bibliographical note

Funding Information:
Acknowledgments: The authors M.K. and K.M. are grateful to Provectus Biopharamceuticals for financial support.

Funding Information:
The MraY inhibitor and some bacteria and mammalian cell lines used in this study were generated or acquired by the NIH-funded program (R01GM114611).The authors M.K. and K.M. are grateful to Provectus Biopharamceuticals for financial support.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Antibacterial activity
Biofilms
Drugresistant gram-positive pathogens
High-purity form of rose bengal (HP-RB)
Methicillin-resistant Staphylococcus aureus
Multidrug-resistant bacteria
Rose bengal (RB)
Vancomycin resistant Enterococcus faecium
Whole genome analyses

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules27010322

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title = "Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies",

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 multidrugresistant (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{\textquoteright}s bactericidal activity under dark conditions.",

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author = "Michio Kurosu and Katsuhiko Mitachi and Junshu Yang and Pershing, {Edward V.} and Horowitz, {Bruce D.} and Wachter, {Eric A.} and Lacey, {John W.} and Yinduo Ji and Rodrigues, {Dominic J.}",

note = "Funding Information: Acknowledgments: The authors M.K. and K.M. are grateful to Provectus Biopharamceuticals for financial support. Funding Information: The MraY inhibitor and some bacteria and mammalian cell lines used in this study were generated or acquired by the NIH-funded program (R01GM114611).The authors M.K. and K.M. are grateful to Provectus Biopharamceuticals for financial support. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/molecules27010322",

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T2 - An Application of a Synthetic Dye in Antibacterial Therapies

AU - Kurosu, Michio

AU - Mitachi, Katsuhiko

AU - Yang, Junshu

AU - Pershing, Edward V.

AU - Horowitz, Bruce D.

AU - Wachter, Eric A.

AU - Lacey, John W.

AU - Ji, Yinduo

AU - Rodrigues, Dominic J.

N1 - Funding Information: Acknowledgments: The authors M.K. and K.M. are grateful to Provectus Biopharamceuticals for financial support. Funding Information: The MraY inhibitor and some bacteria and mammalian cell lines used in this study were generated or acquired by the NIH-funded program (R01GM114611).The authors M.K. and K.M. are grateful to Provectus Biopharamceuticals for financial support. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - 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 multidrugresistant (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.

AB - 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 multidrugresistant (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.

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KW - Rose bengal (RB)

KW - Vancomycin resistant Enterococcus faecium

KW - Whole genome analyses

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Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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