Persister bacteria manipulate intracellular pH for surviving antibiotic treatment

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

Scientists at the University of Exeter 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.

The Exeter University research team 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.

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."

Dr Stefano Pagliara, Biophysicist in the Living Systems Institute, University of Exeter

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.

Source:
Journal reference:

Goode, O., et al. (2021) Persister Escherichia coli Cells Have a Lower Intracellular pH than Susceptible Cells but Maintain Their pH in Response to Antibiotic Treatment. mBio. doi.org/10.1128/mBio.00909-21.

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