Virtual Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2022

A drug candidate for Alzheimer's and Huntington's disease, PBT2, can be repurposed to render Neisseria gonorrhoeae susceptible to cationic antimicrobial peptides. (82527)

Freda Jen 1 , Ibrahim El-Deeb 1 , Arun Everest-Dass 1 , Sanjesh Singh 1 , Thomas Haselhorst 1 , Yaramah Zalucki 1 , Jennifer Edwards 2 , Mark Walker 3 , Mark von Itzstein 1 , Michael Jennings 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, 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, Columbus, OH, USA
  3. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia

Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea, which has a global incidence of 106 million cases per year. No vaccine is available to prevent the disease, and the emergence of multidrug resistant (MDR) strains makes N. gonorrhoeae an immediate public health threat. Here, we show that the chemical synergy between an ionophore, PBT2 and zinc can reverse the intrinsic resistance of N. gonorrhoeae to cationic antibiotic peptides polymyxin B or colistin.  PBT/zinc can also increase the susceptibility of N. gonorrhoeae to two cationic antimicrobial peptides, LL-37 and PG-1, which are naturally present in mammals. The emergence of bacterial strains that are resistant to available antimicrobials is a current health emergency. Treatment with PBT2/zinc to sensitize the bacterium to antimicrobial peptides may represent a new strategy to treat MDR N. gonorrhoeae infections and reinvigorate the use of currently available antibiotics.