Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction.
MexXY is an inducible efflux system that contributes to the natural resistance of Pseudomonas aeruginosa to antibiotics. Experiments involving real-time PCR after reverse transcription in reference strain PAO1 showed concentration-dependent induction of gene mexY by various ribosome inhibitors (e.g., chloramphenicol, tetracycline, macrolides, and aminoglycosides) but not by antibiotics acting on other cellular targets (e.g., beta-lactams, fluoroquinolones). Confirming a functional link between the efflux system and the translational machinery, ribosome protection by plasmid-encoded proteins TetO and ErmBP increased the resistance of a DeltamexAB-oprM mutant of PAO1 to tetracycline and erythromycin, respectively, as well as the concentrations of both drugs required to induce mexY. Furthermore, spontaneous mutations resulting in specific resistance to dihydrostreptomycin or spectinomycin also raised the minimal drug concentration for mexXY induction in strain PAO1. While strongly upregulated in a PAO1 mutant defective in gene mexZ (which codes for a putative repressor of operon mexXY), gene mexY remained inducible by agents such as tetracycline, chloramphenicol, and spectinomycin, suggesting additional regulatory loci for mexXY. Altogether, these data demonstrate physiological interplays between MexXY and the ribosome and are suggestive of an alternative function for MexXY beyond antibiotic efflux.
Jeannot
Katy
K
Laboratoire de Bactériologie, Hôpital Jean Minjoz, 25030 Besançon Cedex, France.
Sobel
Mara L
ML
El Garch
Farid
F
Poole
Keith
K
Plésiat
Patrick
P
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D004096:Dihydrostreptomycin Sulfate / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics*; D012270:Ribosomes / Q000187:drug effects*; D013307:Streptomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C402791:MexXY protein, Pseudomonas aeruginosa; D004096:Dihydrostreptomycin Sulfate; D013307:Streptomycin