Experimental evolution of Pseudomonas aeruginosa to colistin in spatially confined microdroplets identifies evolutionary trajectories consistent with adaptation in microaerobic lung environments

mBio. 2023 Dec 19;14(6):e0150623. doi: 10.1128/mbio.01506-23. Epub 2023 Oct 17.

Abstract

Antibiotic resistance remains one of the great challenges confronting public health in the world today. Individuals with compromised immune systems or underlying health conditions are often at an increased for bacterial infections. Patients with cystic fibrosis (CF) produce thick mucus that clogs airways and provides a very favorable environment for infection by bacteria that further decrease lung function and, ultimately, mortality. CF patients are often infected by bacteria such as Pseudomonas aeruginosa early in life and experience a series of chronic infections that, over time, become increasingly difficult to treat due to increased antibiotic resistance. Colistin is a major antibiotic used to treat CF patients. Clinical and laboratory studies have identified PmrA/PmrB and PhoP/PhoQ as responsible for increased resistance to colistin. Both have been identified in CF patient lungs, but why, in some cases, is it one and not the other? In this study, we show that distinct evolutionary trajectories to colistin resistance may be favored by the microaerobic partitioning found within the damaged CF lung.

Keywords: Pseudomonas aeruginosa; colistin; cystic fibrosis; experimental evolution; microfluidics.

MeSH terms

  • Adaptation, Physiological
  • Aerobiosis
  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Colistin* / pharmacology
  • Cystic Fibrosis* / microbiology
  • Drug Resistance, Bacterial*
  • Humans
  • Lung* / microbiology
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa* / drug effects
  • Pseudomonas aeruginosa* / genetics

Substances

  • Colistin
  • Anti-Bacterial Agents
  • Bacterial Proteins