Mutations in 23S rRNA confer resistance against azithromycin in Pseudomonas aeruginosa

Area of Science:

• Microbiology
• Genetics
• Medical Science

Background:

• Antibiotic-resistant *Pseudomonas aeruginosa* poses a significant challenge in managing chronic airway infections, particularly in cystic fibrosis (CF) patients.
• Azithromycin is frequently used in CF patient treatment, making resistance a critical issue.

Purpose of the Study:

• To investigate the genetic basis of azithromycin resistance in clinical isolates of *Pseudomonas aeruginosa*.
• To characterize the role of specific mutations in the 23S ribosomal RNA (rRNA) gene in conferring azithromycin resistance.

Main Methods:

• Analysis of clinical *P. aeruginosa* DK2 isolates for azithromycin resistance.
• Identification of mutations within domain V of the 23S rRNA gene using standard genetic sequencing.
• Introduction of identified mutations (A2058G and C2611T) into the *P. aeruginosa* PAO1 strain to assess their functional impact on resistance.

Main Results:

• Azithromycin resistance was observed in clinical *P. aeruginosa* DK2 isolates.
• Specific mutations, namely A2058G, A2059G, and C2611T (in *Escherichia coli* numbering), in domain V of the 23S rRNA gene were found to be associated with this resistance.
• Experimental introduction of the A2058G and C2611T mutations into the *P. aeruginosa* PAO1 strain successfully conferred azithromycin resistance.

Conclusions:

• Specific mutations in the 23S rRNA gene are responsible for azithromycin resistance in *Pseudomonas aeruginosa*.
• These findings provide a molecular understanding of azithromycin resistance mechanisms in *P. aeruginosa*, crucial for guiding treatment strategies in cystic fibrosis patients.