Transcription-associated mutation of lasR in Pseudomonas aeruginosa
Chao Wang1, John R McPherson2, Lian-Hui Zhang3
1Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 169610, Singapore.
Abstract:
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.
Insights
Transcription strength influences mutations in the Pseudomonas aeruginosa lasR gene, a key virulence regulator. This finding offers new insights into how this opportunistic pathogen develops antibiotic resistance during infections.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen affecting immunocompromised individuals, such as cystic fibrosis and cancer patients.
- The lasR gene regulates P. aeruginosa virulence in response to environmental cues and is frequently mutated during infection.
- Mutations in lasR provide a growth advantage and increase antibiotic resistance, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the hypothesis that transcription strength is a contributing factor in lasR mutagenesis.
- To explore the mechanistic basis of lasR mutations in P. aeruginosa.
Main Methods:
- Engineered P. aeruginosa strains with varying lasR transcription strengths.
- Utilized next-generation sequencing for unbiased monitoring of lasR mutations.
Main Results:
- Demonstrated that transcription strength is a significant factor influencing lasR mutagenesis.
- Identified a potential mechanism driving the evolution of antibiotic resistance in P. aeruginosa.
Conclusions:
- Transcription strength plays a deterministic role in the mutagenesis of the lasR gene in P. aeruginosa.
- Findings provide novel insights into bacterial pathogenesis and the development of antibiotic resistance.
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