The Urgent Global Crisis of Antimicrobial Resistance

Antimicrobial resistance (AMR), often referred to as the silent pandemic, poses one of the greatest threats to modern medicine. Bacteria that no longer respond to standard antibiotics are causing infections that were once easily treatable to become deadly. Globally, AMR directly led to 1.27 million deaths in 2019, with projections estimating up to 10 million annual deaths by 2050 if unchecked. In low- and middle-income countries like those in Africa, the burden is disproportionately heavy, with resistance rates to key antibiotics exceeding 70% in some regions for Gram-negative pathogens.

In South Africa, the situation is particularly alarming. Recent data indicates around 8,500 deaths directly attributed to AMR in 2021 alone, with hospital-acquired infections driving much of the toll. Common bacteria such as Klebsiella pneumoniae, a Gram-negative superbug, top the list of priority pathogens due to their multi-drug resistance profiles. These organisms thrive in healthcare settings, complicating treatments for pneumonia, bloodstream infections, and urinary tract infections.

Gram-Negative Bacteria: Why They Are So Hard to Kill

Gram-negative bacteria, named for their staining properties under a microscope, feature a double membrane structure that acts as a formidable barrier. The outer membrane blocks most antibiotics from entering the cell, while efflux pumps actively expel any that penetrate. This makes them inherently more resistant than Gram-positive bacteria, which have a single membrane.

Klebsiella pneumoniae exemplifies this challenge. Responsible for a significant portion of AMR-related deaths worldwide, it has evolved resistance to carbapenems—the last-resort antibiotics. In South African hospitals, resistance rates to third-generation cephalosporins exceed 50%, underscoring the need for entirely new therapeutic strategies.

Prof Erick Strauss: A Pioneer in Chemical Biology at Stellenbosch University

At the forefront of this battle is Professor Erick Strauss, Head of the Department of Biochemistry at Stellenbosch University (SU) and co-director of the Africa Centre for Therapeutic Innovation (ACTI). A chemical biologist with a track record in drug discovery, Strauss has shifted focus from traditional inhibitors to groundbreaking protein degradation techniques. His prior work on multi-drug-resistant tuberculosis, funded by the Gates Foundation, laid the groundwork for tackling Gram-negative threats.

SU, one of South Africa's premier research institutions, provides the ideal ecosystem. Located in the Western Cape, it boasts world-class facilities and interdisciplinary collaboration, positioning it as a hub for therapeutic innovation in Africa. For aspiring researchers, opportunities abound in research jobs within biochemistry and microbiology at institutions like SU.

The Revolutionary BacPROTAC Approach Explained

Strauss's innovation centers on Bacterial PROteolysis TArgeting Chimeras (BacPROTACs), adapted from PROTACs used in cancer therapy. Traditional antibiotics inhibit bacterial processes like protein synthesis or cell wall building, but bacteria quickly mutate to evade them. BacPROTACs, however, force bacteria to destroy their own essential proteins.

• Step 1: Design a bifunctional molecule—one end binds a specific bacterial target protein, the other recruits the bacterium's own degradation machinery, such as the ClpXP protease complex.
• Step 2: The proximity triggers ubiquitination-like tagging and subsequent degradation of the target protein inside the bacterial cell.
• Step 3: The BacPROTAC molecule is released and recycled, acting repeatedly like a 'fishing rod with bait' to catch more targets, potentially requiring lower doses and offering prolonged effects.

This mechanism circumvents resistance by not blocking processes but eliminating critical components, reducing the likelihood of evolutionary escape.

Gr-ADI Consortium: A $60 Million Global Collaboration

The Gram-Negative Antibiotic Discovery Innovator (Gr-ADI) is a landmark US$60 million initiative funded by the Bill & Melinda Gates Foundation, Novo Nordisk Foundation, and Wellcome over three years. Launched as part of a $300 million partnership, it unites 18 projects across 17 countries, with teams sharing data to accelerate discovery.

Strauss leads one of two African teams, alongside collaborators from SU's Medical Microbiology (Prof Andrew Whitelaw), Rhodes University (Prof Adrienne Edkins), University of Ghana, and Spain's Ersilia Open-Source Initiative. Prof Willem van Otterlo at SU handles synthesis. This first-of-its-kind consortium emphasizes open collaboration to overcome siloed research.

African Leadership in the Fight Against AMR

Africa bears 25% of the global AMR burden despite comprising 18% of the population. Strauss's selection highlights the continent's rising research prowess. The other African team, led by Prof Stephen Dela Ahator at the University of Ghana, complements efforts, fostering pan-African synergy.

In South Africa, where HIV and TB co-infections exacerbate AMR, initiatives like ACTI at SU integrate drug discovery with clinical needs. This positions SA universities as key players, attracting global funding and talent.

Implications for South African Higher Education and Research

This funding validates SU's strategic investments in science faculties, enhancing postgraduate training and postdoctoral opportunities. Postdoc positions in infectious disease research are increasingly vital, offering pathways for early-career scientists to contribute to global health.

The Gr-ADI project will build local capacity, from chemical synthesis to AI-driven modeling via Ersilia, empowering SA's higher education sector. Explore university jobs in South Africa to join this momentum.

Real-World Case Studies and Statistics

In South Africa, a 2025 WHO report noted 1 in 5 infections resistant in the African region, with Klebsiella topping hospital lists. A KwaZulu-Natal outbreak saw 40% mortality from carbapenem-resistant strains. Strauss's approach targets these exact vulnerabilities.

Globally, Tufts and Oxford teams in Gr-ADI pursue complementary strategies, but Africa's focus on high-burden pathogens ensures equitable solutions.

Challenges, Solutions, and Future Outlook

Challenges include scaling synthesis for Gram-negative delivery and clinical translation. Solutions lie in Gr-ADI's shared platform and prior TB successes. Over three years, expect lead compounds entering preclinical testing, potentially revolutionizing treatments by 2030.

For South African higher ed, this cements SU's leadership, inspiring similar grants. Students and faculty can engage via academic career advice.

Photo by Martijn Baudoin on Unsplash

Opportunities and Calls to Action

This initiative underscores the role of universities in solving global crises. Aspiring professors and researchers should explore professor jobs, higher ed jobs, and rate my professor for insights. Visit university jobs or post openings at post a job to connect with talent driving change.