Research sheds new light on antibiotic resistance

02 August 2023

Antimicrobial resistance (AMR) is one of the top ten global public health threats facing humanity today according to WHO. New research from Magdalen Fellow by Examination Dr Rachel Wheatley sheds new light on this increasingly deadly problem.

Australian Prime Minister Sir Robert Menzies said that in terms of world well-being, the pharmacologist, pathologist, and Magdalen Fellow Howard Walter Florey ‘was the most important man ever born in Australia’. By isolating and purifying penicillin for general clinical use – building on the work of Sir Alexander Fleming with whom he shared the Nobel Prize in 1945 along with Ernst Chain – Florey is estimated to have saved over 80 million lives.

Since that time, antibiotics, as well as other antimicrobials including antivirals, antifungals and antiparasitics, have become increasingly ineffective as drug-resistance has spread across the globe. The problem is now so serious that the World Health Organisation has declared antimicrobial resistance (AMR) one of the top ten global public health threats facing humanity alongside air pollution and climate change.

However, new research by Dr Rachel Wheatley, the George Grosvenor Freeman Fellow by Examination at Magdalen, and a team at the Department of Biology along with COMBACTE colleagues has shed new light on the development of AMR with the promise of new treatments in the future.

Dr Rachel Wheatley

This is an exciting piece of research for advancing our understanding of antibiotic resistance

Dr Rachel Wheatley

Rachel and the team took samples from 35 Intensive Care Unit patients infected with a species of pathogenic bacteria called Pseudomonous aeruginosa, which can cause serious infections in the lungs. As respiratory infections are one of the largest causes of death as a result of AMR, the team were keen to look for changes in the pathogen’s genome and antibiotic resistance.

In the past, scientists had thought that antibiotic resistance often occurs as a result of new mutations that happen when a single pathogen strain multiplies over the course of an infection, and because of this, clinical microbiology often only looks at one sample per patient. However, in this new study, Rachel and the team took multiple samples (6-12 samples), which revealed something interesting: many patients had multiple strains of Pseudomonous aerPseudomonous aeruginosa in their lungs.

Importantly, they found that resistance to antibiotic treatment increased faster for patients with multiple strains. Antimicrobial resistance increased by ~20% more when patients were infected by multiple strains, and this was due to selection for pre-existing resistant strains rather than selection on new mutations.

“This is an exciting piece of research for advancing our understanding of antibiotic resistance evolution during acute respiratory infections,” said Rachel. “First, we show that mixed strain populations of the pathogen Pseudomonous aeruginosa are surprisingly common in the lungs of ICU patients.

“Then, we show that this has important implications for the emergence of antibiotic resistance. This work has made us think about how many patients we need to be sampling, and how measurements of diversity may be useful in predicting the emergence of resistance.”

You can read ‘Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients’ in Nature Communications.