Global non-profit CARB-X invests US$1.75 million to fight antibiotic resistance

The Global non-profit consortium CARB-X is investing US$1.75 million in the University of Melbourne’s Doherty Institute to fight antibiotic resistance.

The funds will support researchers from the Peter Doherty Institute for Infection and Immunity who are developing a world-first treatment for community-acquired bacterial pneumonia (CABP) that works by overcoming antibiotic resistance.  The Doherty Institute is a joint venture  between the University of Melbourne and the Royal Melbourne Hospital.

The innovative therapeutic will target the bacteria that most commonly cause pneumonia – Streptococcus pneumoniaeHaemophilus influenzae, and Moraxella catarrhalis, by disrupting their ability to resist antibiotic treatment. Making the bacteria susceptible to the drugs will restore the effectiveness of frontline antibiotics.

University of Melbourne’s Professor Christopher McDevitt, Head of Research in the Department of Microbiology and Immunology at the Doherty Institute, along with his team and in collaboration with colleagues at the University of Queensland, is heading the project which could lead to improved treatment outcomes and may provide valuable insights into developing strategies to combat other antibiotic-resistant infections.

CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) has awarded the equivalent of AU$2.68 million to the Doherty Institute to support development of this therapeutic through preclinical studies and, if it proves successful, human clinical trials.

CARB-X is a global non-profit partnership dedicated to supporting early-stage antibacterial research and development. It supports innovative therapeutics, preventatives and rapid diagnostics, is led by Boston University and funded by a consortium of governments and foundations. CARB-X funds only projects that target drug-resistant bacteria highlighted on the US Centers for Disease Control and Prevention Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the World Health Organisation.

Lower respiratory tract infections, including CABP, are among the world’s most deadly communicable diseases. They are estimated to have killed 2.6 million people in 2019 globally, and they cause a substantial mortality, morbidity and economic burden for vulnerable people in low-income countries, where they are the second leading cause of death. Patients with CABP struggle to breathe as their lungs fill with pus and fluid, and they can require hospitalisation and intensive care treatment.

Professor McDevitt says in the century that has almost passed since 1928 when antibiotics in the form of penicillin were developed, changes to the specific bacteria that cause CABP mean the drugs have become significantly less effective.

“Research to develop new drugs is underway, but we’re also seeking to reactivate the workhorse antibiotics whose potency has been reduced by resistance as part of the strategy to deal with CABP and other bacterial diseases,” he says.

More than 400,000 people globally died in 2019 due to lower respiratory tract infections attributable to drug-resistant bacteria, and even in a high-income country like the US, 22 per cent of CABP cases result in treatment failure due to antibiotic resistance.

The CARB-X award supports the development of PBT2, an ionophore therapeutic originally pursued as a potential treatment to restore brain activity in patients with neurodegenerative disorders, including Alzheimer’s and Huntington’s diseases. (Ionophores are chemical compounds that reversibly bind and transport ions through biological membranes).

Studies found that PBT2 is also able to disarm key pathways involved in mechanisms by which bacteria become resistant to frontline antibiotics, like amoxicillin and doxycycline.

Professor McDevitt says his team aim to use the effects of PBT2 on drug-resistant bacteria to restore the ability of common antibiotics to effectively eliminate those bacteria.

Director of the University of Melbourne’s Doherty Institute Laureate Professor Sharon Lewin says CARB-X’s generous support to take this research from lab benches to market is an important milestone. “CARB-X’s support accelerates the pathway for the development of this new therapeutic,” she says.

CARB-X funding for this research is supported by federal funds from: the United States Department of Health and Human Services’ Administration for Strategic Preparedness and Response Biomedical Advanced Research and Development Authority (BARDA), and by awards from Wellcome and Germany’s Federal Ministry of Education and Research (BMBF), the UK Department of Health and Social Care Global Antimicrobial Resistance Innovation Fund (GAMRIF) and the Bill and Melinda Gates Foundation.

First published on 4 October 2023.

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