Ciprofloxacin induction of a susceptibility determinant in Pseudomonas aeruginosa

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• Limited novel antimicrobials and increasing antibiotic resistance pose significant threats to public health.
• Understanding global antibiotic-host interactions is crucial for developing effective therapies.
• Pseudomonas aeruginosa is an intrinsically resistant bacterium often treated with fluoroquinolones.

Purpose of the Study:

• To globally characterize the gene expression response of Pseudomonas aeruginosa to ciprofloxacin.
• To identify specific genetic regions involved in bacterial response and resistance to fluoroquinolones.

Main Methods:

• Custom DNA microarrays were employed to analyze differential gene expression.
• Real-time PCR and lux reporter mutants were used to confirm pyocin gene expression.
• Transmission electron microscopy visualized pyocin-like particles.

Main Results:

• Ciprofloxacin treatment (0.3x and 1x MIC) significantly altered the expression of 941 genes in P. aeruginosa.
• The bacteriophage-like R2/F2 pyocin region showed dramatic up-regulation (7- to 19-fold) with ciprofloxacin exposure.
• Mutants lacking the R2/F2 pyocin region exhibited an 8-fold increase in resistance to ciprofloxacin and other fluoroquinolones.

Conclusions:

• The R2/F2 pyocin region acts as a susceptibility determinant for fluoroquinolones in P. aeruginosa.
• This region, variably present in clinical isolates, represents a potential target for novel antimicrobial strategies.
• The R2/F2 pyocin region is a critical factor mediating fluoroquinolone susceptibility in this pathogen.