03 Oct 2023
Global non-profit CARB-X awards more than AUD$2.6 million to University of Melbourne’s Doherty Institute to fight antibiotic resistance
University of Melbourne researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) are developing a world-first treatment for antibiotic-resistant community-acquired bacterial pneumonia (CABP). The AUD$2.68M (US$1.75M) award by Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) will help accelerate the pathway for the development of this new therapeutic through lead optimisation studies, with further support for preclinical studies and human clinical trials, if it proves successful.
People who contract CABP struggle to breathe as their lungs fill with fluid, which can result in hospitalisation and intensive care treatment. This bacterial disease and other lower respiratory tract infections are among the world’s deadliest communicable diseases. In 2019, drug-resistant bacterial lower respiratory tract infections were responsible for more than 400,000 deaths around the world. In the US, treatment failure occurs in 22 per cent of all CABP cases due to antibiotic resistance.
University of Melbourne’s Professor Christopher McDevitt, Head of Research in the Department of Microbiology and Immunology and co-Lead of the Bacterial and Parasitic Infections Theme at the Doherty Institute, is leading the research into an innovative therapeutic approach that will target the bacteria that most commonly cause CABP – Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis – with the goal of disrupting their ability to resist antibiotic treatment.
In collaboration with colleagues at the University of Queensland, Professor McDevitt and his team aim to improve CABP treatment outcomes and deliver valuable insights into developing new approaches to combatting antimicrobial resistance – one of the most serious threats to global public health.
“Restoring the susceptibility of these pathogens to drug treatment will rescue the effectiveness of commonly used frontline antibiotics,” said Professor McDevitt.
CARBX is a global non-profit partnership dedicated to building a pipeline of high-impact products by supporting innovative, antibacterial development. Led by Boston University and funded by a consortium of governments and foundations, it supports innovative therapeutics, preventatives and rapid diagnostics. CARB-X focuses on infections, and the antibiotic-resistant bacterial pathogens that cause them, that result in the greatest morbidity and mortality globally.
Professor McDevitt explained that, in the century that has nearly passed since antibiotics in the form of penicillin were first discovered, bacteria, including those causing CABP, have developed resistance. As a result, many of the drugs commonly used in clinical settings have become substantially less effective.
“Research to develop new drugs is underway, but we’re aiming to restore the effectiveness of frontline antibiotics whose ability to treat infections has been reduced by resistance. This is a crucial part of a long-term strategy to deal with CABP and other bacterial infections by aiming to preserve the usefulness of our existing antimicrobial defences,” he said.
The CARB-X award to Professor McDevitt supports the development of PBT2, a therapeutic originally developed as a treatment for neurodegenerative disorders including Alzheimer’s and Huntington’s diseases. Although PBT2 did not progress as a treatment for neurodegenerative diseases, studies by Professor McDevitt and his collaborators discovered that PBT2 had the potential to disarm the pathways by which bacteria resist key frontline antibiotics, including amoxicillin and doxycycline.
McDevitt Lab staff working at the bench at the Doherty Institute
Professor McDevitt said his team will develop these findings into a therapeutic strategy to use PBT2 to break drug-resistance and restore the ability of common antibiotics to effectively eliminate those bacteria.
University of Melbourne Laureate Professor Sharon Lewin, Director of the Doherty Institute, said CARB-X’s generous support to take this research from lab benches to market is an important milestone.
“Thanks to CARB-X’s support, Professor McDevitt and his team will be able to accelerate the development of this new therapeutic which will go a long way in improving outcomes for CAPB patients and addressing the global challenge that is antimicrobial resistance,” said Professor Lewin.
Research reported in this article is supported by CARB-X. CARB-X’s funding for this project is provided in part with federal funds from the US Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; under agreement number: 75A50122C00028, and by awards from Wellcome (WT224842), Germany’s Federal Ministry of Education and Research (BMBF), the UK Global Antimicrobial Resistance Innovation Fund (GAMRIF) funded by the UK Government Department of Health and Social Care (DHSC), and the Bill & Melinda Gates Foundation. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders.