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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Multiform antimicrobial resistance from a metabolic mutation.

Sarah M Schrader1, Hélène Botella1,2, Robert Jansen1,3

  • 1Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.

Science Advances
|August 28, 2021
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Summary
This summary is machine-generated.

Scientists found a way to identify bacterial mutants that survive antibiotics. A single gene change in arginine biosynthesis in mycobacteria led to resistance against multiple antibiotics, mediated by WhiB7.

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Area of Science:

  • Microbiology
  • Infectious Diseases
  • Genetics

Background:

  • Bacterial infections pose a significant challenge due to antibiotic resistance mechanisms like persistence and tolerance.
  • Understanding the genetic basis of bacterial high survival is crucial for developing effective treatments.

Purpose of the Study:

  • To develop a novel forward-genetic method for isolating bacterial mutants with high survival rates.
  • To investigate the mechanisms underlying antibiotic resistance, persistence, and tolerance in bacteria.

Main Methods:

  • Developed a forward-genetic screening approach applicable to any culturable bacterial species.
  • Induced mutations in an essential metabolic pathway (arginine biosynthesis) in a mycobacterium.
  • Assessed the survival and resistance profiles of generated mutants against various antibiotics.

Main Results:

  • A single base change in a metabolic pathway gene conferred multiple forms of antibiotic resistance.
  • Perturbation of arginine biosynthesis led to distinct resistance phenotypes mediated by WhiB7 induction.
  • Observed high persistence/tolerance to kanamycin, high survival to rifampicin, and shifted resistance to clarithromycin.

Conclusions:

  • A single genetic alteration can induce broad-spectrum antibiotic resistance and resilience in bacteria.
  • The mediator of multiform resistance, WhiB7, is a potential therapeutic target.
  • Findings offer insights into how sub-lethal antibiotic exposure can drive resistance to multiple drugs.