Transcription-associated mutation of lasR in Pseudomonas aeruginosa

DNA Repair (Amst). 2016 Oct:46:9-19. doi: 10.1016/j.dnarep.2016.09.001. Epub 2016 Sep 13.


Pseudomonas aeruginosa is an opportunistic pathogen which infects cystic fibrosis and cancer patients with compromised immune systems. LasR is a master regulator which controls the virulence of P. aeruginosa in response to bacterial cell-density and host signals. During infection, lasR is frequently mutated, conferring P. aeruginosa a growth advantage in hosts and enhances resistance to widely used antibiotics. However, the mechanistic basis of lasR mutation is not well understood. We have tested here the hypothesis that transcription strength is a contributory determinant of lasR mutagenesis. P. aeruginosa strains with different lasR transcription strengths were therefore engineered and the lasR mutations were monitored unbiasedly using next-generation sequencing technology. Our results suggest that the strength of transcription could be one of the deterministic factors that drive the mutagenesis of lasR in P. aeruginosa, shedding new insights into bacterial infection and antibiotic resistance.

Keywords: Miseq; Next generation sequencing; Pseudomonas aeruginosa; Quorum sensing; Transcription-associated mutation.

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Colony Count, Microbial
  • Drug Resistance, Bacterial
  • Gene Expression Regulation, Bacterial*
  • Genetic Fitness
  • High-Throughput Nucleotide Sequencing
  • Mutation*
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / metabolism
  • Quorum Sensing
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription, Genetic*


  • Bacterial Proteins
  • LasI protein, Pseudomonas aeruginosa
  • LasR protein, Pseudomonas aeruginosa
  • Repressor Proteins
  • Trans-Activators
  • rsaL protein, Pseudomonas aeruginosa