Insertion sequences drive the emergence of a highly adapted human pathogen

Area of Science:

• Microbiology
• Genetics
• Pathogen Adaptation

Background:

• Pseudomonas aeruginosa is an opportunistic pathogen causing severe lung infections.
• Environmental taxonomic outliers of P. aeruginosa are increasingly causing human infections.
• Fatal hemorrhagic pneumonia cases highlight the need to understand P. aeruginosa adaptation.

Purpose of the Study:

• To perform the first genome-wide analysis of a P. aeruginosa outlier causing fatal pneumonia.
• To investigate the role of mobile genetic elements in virulence and antibiotic resistance.
• To understand the adaptation mechanisms of environmental P. aeruginosa to human hosts.

Main Methods:

• Comparative genome, proteome, and transcriptome analyses of sequential patient isolates (CLJ1 and CLJ3).
• Insertion sequence (ISL3-family) characterization and its impact on gene expression.
• Assessment of virulence in the Galleria mellonella larvae model.

Main Results:

• ISL3 insertions disrupted genes for flagella, pili, O-antigens, and hydrogen cyanide production.
• Increased ISL3 insertions in the later isolate (CLJ3) correlated with altered antibiotic susceptibility.
• Disruptions in OprD and AmpD genes affected antibiotic resistance.
• CLJ1 exhibited higher virulence in the Galleria mellonella model.

Conclusions:

• Insertion sequences are key drivers in enhancing the pathogenic potential of P. aeruginosa outliers.
• These mobile genetic elements modulate both virulence and antimicrobial resistance.
• The study elucidates bacterial adaptation from environmental niches to human hosts.