Rethinking Antibiotics: Phages, TB Vaccines, and New Antimicrobial Resistance Strategies

Antimicrobial resistance is rising globally, threatening modern medicine. This Naked Scientists episode surveys how researchers tackle AMR with innovative strategies—from mining old antibiotic pathways for stronger compounds to engineering bacteriophages and developing a next-generation TB vaccine. The discussion explains how resistance emerges, why new antibiotics face economic hurdles, and how novel incentives could accelerate drug development. It also highlights breakthroughs in phage design and a TB vaccine approach that aims to prime the immune system to recognize infected cells, offering fresh hope against TB, a disease that still claims thousands of lives daily. Listeners learn about stewardship, global collaboration, and how lab discoveries may translate into clinical tools.

Introduction and AMR Context

The Naked Scientists podcast examines antimicrobial resistance (AMR) during Antibiotic Awareness Week, highlighting rising resistant infections in England and globally. The discussion sets AMR as a critical, ongoing health crisis that demands new strategies beyond traditional antibiotics. Experts emphasize that resistance emerges as bacteria adapt to antibiotic pressure, underscoring the need for targeted use and smarter stewardship to prolong drug effectiveness.

"antibiotics, when used to kill bacteria, almost by nature challenge those bacteria to find ways to become resistant." - Colin Brown, infectious diseases consultant, UK Health Security Agency

Roadblocks to New Antibiotics

The programme explores why there is an empty antibiotic pipeline despite demand. Economic incentives to develop last-resort drugs are misaligned because doctors aim to preserve new antibiotics for worst-case scenarios. The UK NICE/NHS subscription model is discussed as a pioneering approach to provide steady, long-term incentives to manufacturers, with other jurisdictions eyeing similar schemes. Yet consensus and robust, cross-border adoption remain challenging, meaning the AMR problem will persist for some time.

Mining the Old for the New: Upstream Antibiotics

Scientists are looking upstream in existing manufacturing pathways for novel antibiotic strategies. A case study on methylinomycin A shows that blocking a biosynthetic step in Streptomyces can reveal intermediates with far greater antibacterial activity, sometimes with little chance of resistance developing in test strains. Researchers explain that many antibiotics are produced by soil bacteria, and decoding these pathways can uncover powerful, previously untapped molecules. Lona Alkallaf of Warwick University highlights that understanding the production line may enable the discovery of new active compounds by reconfiguring enzymes and assembly steps.

"the best place to look for the new ones is where you found the old ones." - Lona Alkallaf, University of Warwick

Bacteriophages: Designer Viruses as Therapeutics

Phage therapy is revisited as a viable complement or alternative to antibiotics. Graham Hatful of the University of Pittsburgh discusses synthetic bacteriophages designed through DNA synthesis and assembly technologies. The ability to create designer phages expands the toolkit beyond naturally occurring phages, potentially enabling broader, more effective antibacterial action. The interview traces how synthetic biology platforms enable rapid phage design and testing, with the potential to address stubborn Mycobacteria and other difficult infections.

"the power of being able to do that engineering is really, I think, quite enormous. It feels like the sky's the limit." - Graham Hatful, University of Pittsburgh

TB Vaccines: A New Immune Signal

The episode shifts to vaccine science, presenting advances in tuberculosis (TB) vaccination. MIT researcher Brian Bryson describes a strategy to improve on the century-old BCG vaccine by reintroducing key TB proteins and immune barcodes that infected cells display on their surface. Animal data show that delivering these proteins can reduce bacterial load in mice, suggesting a path toward vaccines that protect adolescents and adults more effectively than BCG. Ongoing head-to-head comparisons with BCG and broader preclinical work are highlighted as essential steps toward clinical translation.

"The best offense is a good defense." - Brian Bryson, MIT

Outlook

The program closes with an optimistic view of the multifaceted approach to AMR, combining stewardship, economic reform, and bold scientific innovations—from engineered phages to expanded vaccine antigens. While immediate clinical impact remains to be proven, these developments illustrate how research can reimagine the antibiotic arsenal and improve outcomes for patients facing drug-resistant infections.