As antibiotic resistance continues to rise worldwide, a Stellenbosch University scientist is helping to pioneer a radically new way to fight some of the world’s deadliest bacteria.
Prof Erick Strauss from Stellenbosch University (SU) has been selected to lead one of only two African research teams participating in a major US$60 million global consortium focused on transforming antibiotic discovery.
The initiative targets Gram-negative bacteria, particularly Klebsiella pneumoniae — one of the leading causes of antimicrobial-resistance (AMR) deaths globally — and represents a significant international investment in new approaches to drug development.
A Global Consortium with a New Model
The funding was announced by the Gates Foundation, Novo Nordisk Foundation and Wellcome, which together committed US$60 million over three years to support 18 research projects across 17 countries.
The projects form part of the Gram-Negative Antibiotic Discovery Innovator (Gr-ADI), a first-of-its-kind consortium designed to accelerate antibiotic discovery through open collaboration. Participating teams will share data, tools and findings rather than working in isolation.
Gr-ADI is also the first investment of a broader US$300 million global health research and development partnership launched by the three philanthropic organisations in 2024.
Why New Antibiotics Are Urgently Needed
Traditional antibiotics work by blocking processes that bacteria need to survive, such as building cell walls or making proteins. When used correctly, these drugs can stop bacteria from multiplying, giving the immune system time to clear the infection.
However, many Gram-negative bacteria have developed resistance to existing antibiotic classes, making infections increasingly difficult to treat. This has created an urgent need for therapies that work in fundamentally different ways, reducing the likelihood that resistance will emerge again.
Klebsiella pneumoniae is a particular concern, as it is a major driver of AMR-related deaths worldwide.
Turning Bacteria Against Themselves
Strauss’s team will explore a novel strategy inspired by advances in cancer research: targeted protein degradation. Instead of merely inhibiting a harmful protein, this approach hijacks a cell’s natural protein-degradation machinery and forces it to destroy the target protein entirely.
This is achieved using specially designed bifunctional molecules called PROTACs. When applied to bacteria, they are known as BacPROTACs — molecules that cause pathogenic bacteria to degrade their own essential proteins.
While PROTACs have been studied as cancer therapies for more than two decades, BacPROTACs were only first described as potential treatments for mycobacterial infections, including tuberculosis, in 2022.
In 2023, a team led by Strauss received Gates Foundation and LifeArc funding to apply this strategy to multi-drug-resistant tuberculosis through the Grand Challenges African Drug Discovery Accelerator.
One potential advantage of BacPROTACs is that the drug is not consumed in the process. Strauss compares it to a “fishing rod with a baited hook”, suggesting lower doses may be effective and that the effects could be longer lasting.
Building African Drug-Discovery Capacity
Strauss’s Gr-ADI team includes collaborators from SU, Rhodes University, the University of Ghana, and the Ersilia Open-Source Initiative in Spain. The second African project is led by Prof Stephen Dela Ahator of the University of Ghana.
The work will begin with Klebsiella pneumoniae, with the longer-term aim of developing a workflow that can be adapted to other validated bacterial drug targets.
For SU, the grant marks a significant investment in its capacity to develop novel therapeutic drugs — and places African science firmly within a global effort to tackle one of modern medicine’s most pressing challenges.
