Researchers discover a new way to reverse the antibiotic resistance

Feeding overcrowded bacteria showed to increase antibiotic susceptibility

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Researchers from the Massachusetts Institute of Technology (MIT) have recently published promising results regarding reversing antibiotic resistance in Molecular Cell. Arnaud Gutierrez and colleagues showed that the activation of cellular respiration is sufficient to sensitize antibiotic refractory bacteria at high densities to drugs targeting DNA topoisomerases (quinolones). This drug class fail to kill bacteria that have grown to high density; yet, the mechanistic basis for this persistence is not clear. The authors reveal that the supplementation of stationary-phase cultures with glucose and a suitable terminal electron acceptor to stimulate respiratory metabolism is sufficient to sensitize cells to quinolone killing, proposing that the nutrient environment and the metabolic state are key components of bacterial persistence phenotypes. This approach was effective to sensitize high-density populations of Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis to quinolones.

Antibiotic resistance is one of the greatest challenges facing mankind, present in every country. Common infections or minor injuries can become fatal, induce longer hospital stays and higher medical costs. Some infections are already no longer treatable with current drugs, since being caused by highly drug-resistant bacteria or fungi. Resistance in E. coli fluoroquinolone antibiotics is highy prevalent. There are several countries where this treatment is now ineffective in more than half of patients (World Health Organization).

Around 700,000 people die each year around the world as a result of antibiotic resistance.

By 2050, some studies predict that this number will rise to 10 million.

Paper highlights:

  • Quinolone antibiotics fail to kill bacterial populations at high density
  • Exhaustion of OXPHOS substrates drives bacterial persistence
  • Carbon and electron acceptor supplementation restores antibiotic activity
  • Metabolic priming of OXPHOS reverses tolerance in diverse bacterial species

Reference: Gutierrez et al., Understanding and Sensitizing Density-Dependent Persistence to Quinolone Antibiotics, Molecular Cell (2017),


Celia Fortuna Rodrigues

PharmD, PhD , University of Porto