Repurposing the Ionophore, PBT2, for Treatment of Multidrug-Resistant Neisseria gonorrhoeae Infections

Freda E-C Jen; Jennifer L Edwards; Ibrahim M El-Deeb; Mark J Walker; Mark von Itzstein; Michael P Jennings

doi:10.1128/aac.02318-21

Repurposing the Ionophore, PBT2, for Treatment of Multidrug-Resistant Neisseria gonorrhoeae Infections

Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0231821. doi: 10.1128/aac.02318-21. Epub 2022 Aug 18.

Authors

Freda E-C Jen¹, Jennifer L Edwards², Ibrahim M El-Deeb¹, Mark J Walker³, Mark von Itzstein¹, Michael P Jennings¹

Affiliations

¹ Institute for Glycomics, Griffith Universitygrid.1022.1, Gold Coast Campus, Queensland, Australia.
² The Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children's Hospital and The Department of Pediatrics, The Ohio State University, Ohio, USA.
³ School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queenslandgrid.1003.2, Queensland, Australia.

Abstract

Multidrug-resistant (MDR) N. gonorrhoeae is a current public health threat. New therapies are urgently needed. PBT2 is an ionophore that disrupts metal homeostasis. PBT2 administered with zinc is shown to reverse resistance to antibiotics in several bacterial pathogens. Here we show that both N. meningitidis and MDR N. gonorrhoeae are sensitive to killing by PBT2 alone. PBT2 is, thus, a candidate therapeutic for MDR N. gonorrhoeae infections.

Keywords: Neisseria gonorrhoeae; Neisseria meningitidis; PBT2; antibiotic resistance; gonorrhoea; ionophore.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Gonorrhea* / drug therapy
Gonorrhea* / microbiology
Humans
Ionophores / pharmacology
Ionophores / therapeutic use
Microbial Sensitivity Tests
Neisseria gonorrhoeae
Neisseria meningitidis*
Zinc

Substances

Anti-Bacterial Agents
Ionophores
Zinc