Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis
David M. P. De Oliveira, Lisa Bohlmann, Trent Conroy, Freda E.‐C. Jen, Arun Everest‐Dass, Karl A. Hansford, Raghu Bolisetti, Ibrahim M. El‐Deeb, Brian M. Forde, Minh‐Duy Phan, Jake A. Lacey, Aimee Tan, Tania Rivera-Hernández, Stephan Brouwer, Nadia Keller, Timothy J. Kidd, Amanda J. Cork, Michelle J. Bauer, Gregory M. Cook, Mark R. Davies, Scott A. Beatson, David L. Paterson, Alastair G. McEwan, Jian Li, Mark A. Schembri, Mark A. T. Blaskovich, Michael P. Jennings, Christopher A. McDevitt, Mark von Itzstein, Mark J. Walker
Abstract
mutation, we successfully demonstrated the efficacy of PBT2 + polymyxin (colistin or FADDI-287) for the treatment of Gram-negative sepsis in immunocompetent mice. In comparison to polymyxin alone, the combination of PBT2 + polymyxin improved survival and reduced bacterial dissemination to the lungs and spleen of infected mice. These data present a treatment modality to break antibiotic resistance in high-priority polymyxin-resistant Gram-negative pathogens.