Antibiotic resistance is one of the most pressing public health challenges and threatens the ability to effectively fight infectious diseases, with around 10 million people predicted to die annually of infections by 2050. 

Is bacterial acidity a key to tackle antimicrobial resistance?

Decreasing bacterial acidity could help reduce antimicrobial resistance by eliminating bacteria that can survive being treated with antibiotics.  

Scientists at the University of Exeter and the Defence Science and Technology Laboratory (Dstl) have developed a novel method, which allows users to measure the pH of individual bacteria before, during and after treatment with antibiotics. 

The research, published in the journal mBio, lays the foundation for understanding the special properties of bacteria that survive being treated with antibiotics, so that new ways of targeting them can be developed. 

This joint research found that even before antibiotic treatment, common infection causing Escherichia coli cells that can survive treatment have a more acidic intracellular pH compared to clonal cells that are eliminated by the antibiotic treatment. These surviving cells are called persisters because they are responsible for persistent bacterial infections and contribute to antibiotic resistance. 

Antibiotic resistance is one of the most pressing public health challenges and threatens the ability to effectively fight infectious diseases, with around 10 million people predicted to die annually of infections by 2050. 

The University of Exeter research team has discovered the mechanisms that permit persisters to have an acidic pH. By measuring the genetic properties of these cells, they found that two cellular processes, namely tryptophan metabolism and carboxylic acid catabolism, are responsible for the low pH measured in persister bacteria. 

Dr Stefano Pagliara, a biophysicist in the Living Systems Institute, leading this research at the University of Exeter, said: “Our findings indicate that the manipulation of the intracellular pH represents a bacterial strategy for surviving antibiotic treatment. Our new data suggest a strategy for developing antibiotics that interfere with key cellular components of persisters and decrease their acidity.” 

This work was funded by the Defence Science and Technology Laboratory [Dstl], the science inside UK Defence and Security. Dr Jonathan David, Dstl Scientist said: “The release of this paper is not only a step forward in our understanding of bacterial strategies to survive antibiotic treatment, but also demonstrates the utility of the microfluidic techniques of Dr Pagliara’s group to study individual bacterium under a range of stresses.  These techniques can be applied to a range of questions of interest to UK Defence and Security.”

The team is now working on expanding this research to find out whether cell acidity is key for antibiotic resistance in other critical bacterial pathogens such as Pseudomonas aeruginosa and Burkholderia pseudomallei and to identify drug molecules that can alter the pH of persister cells before antibiotic treatment. 

"Persister Escherichia coli Cells Have a Lower Intracellular pH than Susceptible Cells but Maintain Their pH in Response to Antibiotic Treatment" is published on Tuesday, July 20th 2021.

The Living Systems Institute is the University of Exeter flagship for fundamental research. The Institute combines biological and physical sciences to make discoveries that will transform future healthcare Living Systems Institute | Living Systems Institute | University of Exeter. 

Date: 20 July 2021