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Sci Rep. 2018 Nov 20;8(1):17130. doi: 10.1038/s41598-018-35594-y.

Antimicrobial Photodynamic Inactivation Mediated by Tetracyclines in Vitro and in Vivo: Photochemical Mechanisms and Potentiation by Potassium Iodide.

Xuan W1,2,3, He Y2,4, Huang L2,3,5, Huang YY2,3, Bhayana B2, Xi L4,6, Gelfand JA7, Hamblin MR8,9,10.

Author information

1
Department of Otorhinolaryngology, Head and Neck Surgery, First Clinical Medical College and Hospital, Guangxi University of Chinese Medicine, Nanning, China.
2
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
3
Department of Dermatology, Harvard Medical School, Boston, MA, USA.
4
Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
5
Department of Infectious Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, China.
6
Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, China.
7
Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. JGELFAND@mgh.harvard.edu.
8
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA. Hamblin@helix.mgh.harvard.edu.
9
Department of Dermatology, Harvard Medical School, Boston, MA, USA. Hamblin@helix.mgh.harvard.edu.
10
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. Hamblin@helix.mgh.harvard.edu.

Abstract

Tetracyclines (including demeclocycline, DMCT, or doxycycline, DOTC) represent a class of dual-action antibacterial compounds, which can act as antibiotics in the dark, and also as photosensitizers under illumination with blue or UVA light. It is known that tetracyclines are taken up inside bacterial cells where they bind to ribosomes. In the present study, we investigated the photochemical mechanism: Type 1 (hydroxyl radicals); Type 2 (singlet oxygen); or Type 3 (oxygen independent). Moreover, we asked whether addition of potassium iodide (KI) could potentiate the aPDI activity of tetracyclines. High concentrations of KI (200-400 mM) strongly potentiated (up to 5 logs of extra killing) light-mediated killing of Gram-negative Escherichia coli or Gram-positive MRSA (although the latter was somewhat less susceptible). KI potentiation was still apparent after a washing step showing that the iodide could penetrate the E. coli cells where the tetracycline had bound. When cells were added to the tetracycline + KI mixture after light, killing was observed in the case of E. coli showing formation of free molecular iodine. Addition of azide quenched the formation of iodine but not hydrogen peroxide. DMCT but not DOTC iodinated tyrosine. Both E. coli and MRSA could be killed by tetracyclines plus light in the absence of oxygen and this killing was not quenched by azide. A mouse model of a superficial wound infection caused by bioluminescent E. coli could be treated by topical application of DMCT and blue light and bacterial regrowth did not occur owing to the continued anti biotic activity of the tetracycline.

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