Antimicrobials Are a Photodynamic Inactivation Adjuvant for the Eradication of Extensively Drug-Resistant Acinetobacter baumannii

Agata Wozniak; Aleksandra Rapacka-Zdonczyk; Nico T. Mutters; Mariusz Grinholc

doi:10.3389/fmicb.2019.00229

Frontiers in Microbiology (Feb 2019)

Antimicrobials Are a Photodynamic Inactivation Adjuvant for the Eradication of Extensively Drug-Resistant Acinetobacter baumannii

Agata Wozniak,
Aleksandra Rapacka-Zdonczyk,
Nico T. Mutters,
Mariusz Grinholc

Affiliations

Agata Wozniak: Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
Aleksandra Rapacka-Zdonczyk: Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
Nico T. Mutters: Institute for Infection Prevention and Hospital Epidemiology, Medical Center – Faculty of Medicine, University of Freiburg, Freiburg, Germany
Mariusz Grinholc: Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland

DOI: https://doi.org/10.3389/fmicb.2019.00229
Journal volume & issue: Vol. 10

Abstract

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The worldwide emergence of extensively drug resistant (XDR) Acinetobacter baumannii has reduced the number of antimicrobials that exert high bactericidal activity against this pathogen. This is the reason why many scientists are focusing on investigations concerning novel non-antibiotic strategies such as antimicrobial photodynamic inactivation (aPDI) or the use of antimicrobial blue light (aBL). Therefore, the aim of the current study was to screen for antimicrobial synergies of routinely used antibiotics and phototherapies, including both aPDI involving exogenously administered photosensitizing molecules, namely, rose bengal, and aBL, involving excitation of endogenously produced photoactive compounds. The synergy testing was performed in accordance with antimicrobial susceptibility testing (AST) standards, including various methodological approaches, i.e., antibiotic diffusion tests, checkerboard assays, CFU counting and the evaluation of postantibiotic effects (PAEs). We report that combining antimicrobials and aPDI/aBL treatment led to a new strategy that overcomes drug resistance in XDR A. baumannii, rendering this pathogen susceptible to various categories of antibiotics. Sublethal aPDI/aBL treatment in the presence of sub-MIC levels of antimicrobials effectively killed A. baumannii expressing drug resistance to studied antibiotics when treated with only antibiotic therapy. The susceptibility of XDR A. baumannii to a range of antibiotics was enhanced following sublethal aPDI/aBL. Furthermore, 3′-(p-aminophenyl) fluorescein (APF) testing indicated that significantly increased reactive oxygen species production upon combined treatment could explain the observed synergistic activity. This result represents a conclusive example of the synergistic activity between photodynamic inactivation and clinically used antimicrobials leading to effective eradication of XDR A. baumannii isolates and indicates a potent novel therapeutic approach.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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