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Antibacterial effect of rose bengal against colistin-resistant gram-negative bacteria

The Journal of Antibiotics volume 76, pages 416–424 (2023)Cite this article

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Abstract

Increasing drug resistance in Gram-negative bacteria presents significant health problems worldwide. Despite notable advances in the development of a new generation of β-lactams, aminoglycosides, and fluoroquinolones, it remains challenging to treat multi-drug resistant Gram-negative bacterial infections. Colistin (polymyxin E) is one of the most efficacious antibiotics for the treatment of multiple drug-resistant Gram-negative bacteria and has been used clinically as a last-resort option. However, the rapid spread of the transferable gene, mcr-1 which confers colistin resistance by encoding a phosphoethanolamine transferase that modifies lipid A of the bacterial membrane, threatens the efficacy of colistin for the treatment of drug-resistant bacterial infections. Colistin-resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae often reduce their susceptibility to other anti-Gram-negative bacterial agents. Thus, drugs effective against colistin-resistant strains or methods to prevent the acquisition of colistin-resistance during treatment are urgently needed. To perform cell-based screenings of the collected small molecules, we have generated colistin-resistant strains of E. coli, A. baumannii, K. pneumoniae, P. aeruginosa, and S. enterica Typhimurium. In-house MIC assay screenings, we have identified that rose bengal (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein) is the only molecule that displays unique bactericidal activity against these strains at low concentrations under illumination conditions. This article reports the antibacterial activity of a pharmaceutical-grade rose bengal against colistin-resistant Gram-negative bacteria.

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Acknowledgements

We MK and KM are grateful to Provectus Biopharmaceuticals for financial support. M. K. thanks UTRF (University of Tennessee Health Science Center) for generous financial support (Innovation award R079700292). The wild-type bacterial strains used here were obtained through BEI Resources, NIAID, NIH.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN, 38163, USA

    Michio Kurosu & Katsuhiko Mitachi

  2. Provectus Biopharmaceuticals, Inc., 800 S. Gay Street, Suite 1610, Knoxville, TN, 37929, USA

    Edward V. Pershing, Bruce D. Horowitz, Eric A. Wachter, John W. Lacey III & Dominic J. Rodrigues

  3. Department of Veterinary and Biomedical Sciences, University of Minnesota, 205 VSB, 1971 Commonwealth Avenue, St. Paul, MN, 55108, USA

    Yinduo Ji

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Correspondence to Michio Kurosu.

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Kurosu, M., Mitachi, K., Pershing, E.V. et al. Antibacterial effect of rose bengal against colistin-resistant gram-negative bacteria. J Antibiot 76, 416–424 (2023). https://doi.org/10.1038/s41429-023-00622-1

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