As a former microbiologist, with a strong interest in bacterial cell walls and antibiotics, it has been interesting to observe how the topic of antimicrobial resistance (AMR) has ebbed and flowed in research, and public consciousness over the years; on both a national and global scale. World AMR Awareness Week a few weeks ago prompted me to reflect on where we are now, and where we’ve come from.
Most antibiotics are based on naturally occurring compounds, produced by fungi or bacteria themselves. These chemicals are part of a panel of approaches that many microorganisms use to establish and maintain their niche in whatever environment they favour, dealing with other species trying to invade their territory by releasing antibiotics to counter them. So when Alexander Fleming first discovered penicillin in 1928, what he had captured on an agar plate was the ongoing fungal-bacterial warfare that has surrounded us all for thousands of years.
This discovery, and the work that followed it, led to the identification of a whole range of antibiotics based on naturally produced substances. For example, around a third of clinically relevant antibiotics, including streptomycin and chloramphenicol, are derived from species of the bacteria Streptomyces.
The emergence of these drugs has had a massive impact on the world, creating (for those who had the wealth to afford them) treatment options for a range of diseases that were previously deadly. But the natural source of antibiotics comes with one major downside. As much as fungi and bacteria have a range of innate weaponry to defend their positions; other fungi and bacteria also have a range of defence mechanisms aka ‘antimicrobial resistance’ that can make them impervious to these weapons. In the natural world, whether by a thermal vent or on the soil surface, the balance between attack and defence, simply maintains the ecological status quo – giving discrete bacterial communities defined niches with perhaps the odd skirmish around the periphery. But once some of these bacteria are on, or in, the human body, it can be a very different story.
In many ways it is perhaps surprising that AMR did not become a widespread challenge sooner. Bacteria have a tough life, and having AMR genes should provide a strong competitive advantage. But perhaps you’re not competing against a species that produces antibiotics; or perhaps the burden of maintaining those AMR genes as part of your one bacterial chromosome isn’t worth it.
The issue arises when bacteria, AMR, and humans using antibiotics, meet. As antibiotic use increased exponentially in the Global North after the second world war, not only for humans but also for animals (including as growth promoters), the identification of AMR also rose. From the golden age of the 1950s when penicillin was still a relative novelty, right through the 1980s – AMR continued to rise, gradually affecting more and more people and their health outcomes. Today the World Health Organisation (WHO) reports that AMR has been directly responsible for over one million deaths, and contributed to almost five million deaths, in just a single year.
Researching vancomycin resistance in enterococci in the early 2000s for my PhD, certainly didn’t feel like working on a key health challenge of global significance. Although the AMR research community was regularly raising the risks of over-prescription of antibiotics in primary care settings, the risks of antibiotic use to boost the outputs of industrial-scale farming, and the risks of hospital-acquired infections for even previously healthy individuals – the response to this from funders, governments and public health organisations, appeared to be ambiguous at best.
As the need for new classes and types of antibiotics appeared to decline, this was matched by a downturn in investment from big pharma; and the gaps this was leaving in our drug development pipelines, and the implications for global health, were not seen to be significant.
However, in 2024, for many reasons, we find ourselves in a different world. If the Covid-19 pandemic has taught us (including global political and health leaders) anything, it’s that national borders cannot address global health emergencies. And that is very much what AMR is.
The WHO have recently issued a political declaration stating that AMR “is one of the most urgent global health threats and development challenges and demands immediate action to safeguard our ability to treat human, animal, and plant diseases, as well as to enhance food safety, food security and nutrition, foster economic development, equity and a healthy environment”.
In the UK, much of this recognition was driven by Dame Sally Davies, the government’s Chief Medical Officer between 2010-2019, and currently the UK’s Special Envoy of Antimicrobial Resistance. Her voice on this matter catalysed the transformation of AMR from something only those with a strong interest in cell walls and peptidoglycan precursors (NB other modes of antibiotic action are available) were concerned about; to a topic that was on our national health agenda.
It was recently World AMR Awareness Week. The relevance of AMR joining Stars Wars Day or Cat Appreciation Week in the ‘calendar of things’, that is mostly driven by the internet and/or product marketing, is an open question. But in terms of profile-raising for a global issue, I view it as a notable marker.
Our work across Wellcome Connecting Science, within the Wellcome Sanger Institute, and with our funders Wellcome, are all part of the forward momentum to address the challenge of AMR. In Connecting Science our focus is on understanding how we can support effective identification, monitoring and surveillance (particularly in Global South locations) through building capacity, skills and knowledge.
Collaborating with research leaders in the Institute’s Parasites and Microbes programme ensures that there is an established pathway for translating new and emerging AMR knowledge into formats that can be shared with relevant research, policy, and public health communities. Our outputs here range from online courses with broad global reach; to targeted, hands-on, intensive training for defined groups of regional health professionals. Working with Wellcome-funded global networks such as ACORN brings our training expertise directly to those who are best placed to understand where they can apply new approaches with the most impact – you can hear from some of our course collaborators and participants here. And partnering with organisations such as WHO, via the International Pathogen Surveillance Network, enables us to understand and analyse training gaps at both strategic and grassroots levels.
AMR is not a linear challenge; addressing it will require complex actions spanning from behaviour change to creating new R&D models, which will all need to flex and adapt based on regional needs and perspectives. But it’s probably worth remembering that resistance to vancomycin is caused by a change to one, single hydrogen bond. Vancomycin-resistant enterococci are a real world example of how a small change can ultimately lead to major downstream consequences. Whether these consequences are positive or negative, is really up to us.