An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii

Authors:

David M.P. De Oliveira1 and Mark J. Walker1

doi: 10.15698/mic2022.03.772
Volume 9, pp. 69 to 71, published 15/02/2022.

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Affiliations:

1 The University of Queensland, School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, Brisbane, QLD, Australia.

Keywords: 

ionophore, PBT2, antimicrobial resistance, Acinetobacter baumannii, tetracyclines

Corresponding Author(s):

Prof. Mark Walker, School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, QLD 4072, Australia; Tel: +61-7-33461623; Fax: +61-7-33654273; mark.walker@uq.edu.au

Conflict of interest statement:

MJW holds an intellectual property interest in this work (PCT/AU2018/051116).

Please cite this article as:

David M.P. De Oliveira and Mark J. Walker (2022). An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii. Microbial Cell 9(3): 69-71. doi: 10.15698/mic2022.03.772

© 2022 De Oliveira and Walker. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

Within intensive care units, multi-drug resistant Acinetobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multi-drug resistant A. baumannii infections.