Chemical Synergy between Ionophore PBT2 and Zinc Reverses Antibiotic Resistance

Author:

Bohlmann Lisa1,De Oliveira David M. P.1,El-Deeb Ibrahim M.2,Brazel Erin B.3ORCID,Harbison-Price Nichaela4,Ong Cheryl-lynn Y.1,Rivera-Hernandez Tania1,Ferguson Scott A.4,Cork Amanda J.1,Phan Minh-Duy1ORCID,Soderholm Amelia T.1,Davies Mark R.5ORCID,Nimmo Graeme R.6,Dougan Gordon7,Schembri Mark A.1ORCID,Cook Gregory M.4,McEwan Alastair G.1,von Itzstein Mark2ORCID,McDevitt Christopher A.3ORCID,Walker Mark J.1

Affiliation:

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

2. Institute for Glycomics, Griffith University, Brisbane, QLD, Australia

3. Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia

4. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand

5. Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia

6. Pathology Queensland Central Laboratory, Brisbane, QLD, Australia

7. Wellcome Trust Sanger Institute, Hinxton, United Kingdom

Abstract

The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore, Streptococcus pyogenes , a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, “On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you.”

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference37 articles.

1. World Health Organization. 2017. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. World Health Organization, Geneva, Switzerland. http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf?ua=1.

2. EARS-Net. 2018. European Antimicrobial Resistance Surveillance Network (EARS-Net). http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/Pages/index.aspx.

3. Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA. https://www.cdc.gov/drugresistance/biggest_threats.html.

4. Center for Disease Dynamics, Economics & Policy. 2015. The state of the world’s antibiotics, 2015. Center for Disease Dynmics, Economics & Policy, Washington, DC. https://cddep.org/sites/default/files/swa_2015_final.pdf.

5. A review of global initiatives to fight antibiotic resistance and recent antibiotics׳ discovery

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