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Bacterial evolution of antibiotic hypersensitivity.

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Collateral sensitivity, where antibiotic resistance increases susceptibility to other drugs, is common. Mutations reducing proton-motive force (PMF) in E. coli cause resistance and hypersensitivity to other antibiotics.

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genetics

Background:

  • Antibiotic resistance often leads to cross-resistance, increasing susceptibility to multiple drugs.
  • Collateral sensitivity, where resistance to one antibiotic enhances sensitivity to others, is poorly understood.

Purpose of the Study:

  • To investigate the frequency and mechanisms of collateral sensitivity during antibiotic resistance evolution.
  • To explore the genetic basis of collateral sensitivity in Escherichia coli.

Main Methods:

  • Large-scale laboratory evolution experiments using Escherichia coli.
  • Whole-genome sequencing of evolved strains to identify resistance mechanisms.
  • Fitness assays in the presence of various antibiotics.

Main Results:

  • Collateral sensitivity frequently occurs during antibiotic resistance evolution.
  • Populations adapted to aminoglycosides showed significantly reduced fitness with other antibiotics.
  • Identified mutations affecting proton-motive force (PMF) as a mechanism for aminoglycoside resistance and collateral sensitivity.

Conclusions:

  • Genetic adaptations conferring antibiotic resistance can paradoxically increase sensitivity to other antimicrobial agents.
  • Reduced PMF and its impact on efflux pumps are key mechanisms driving collateral sensitivity.
  • Understanding these trade-offs provides insights into the evolution of antimicrobial resistance.