Amino Acid Substitutions Account for Most MexS Alterations in ClinicalnfxCMutants of Pseudomonas aeruginosa

What is it about?

This work described for the first time a collection of clinical strains of Pseudomonas aeruginosa overproducing the efflux system MexEF-OprN which accounts for resistance to chloramphenicol, trimethoprim and fluoroquinolones antibiotics. We explored the genetic events responsible for MexEF-OprN overproduction and found that most of these clinical strains harbor single amino acid substitutions in protein MexS. This substitutions probably alter the enzymatic activity of MexS which could serve as positive signal to pump production. We also found that for nearly half of these strains, any of the genes known to regulate mexEF-oprN efflux operon is mutated or altered indirectly showing that there are still unknown loci capable to activate this operon.

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Why is it important?

Characterization of multi-drug resistant strains is necessary to understand which mechanisms participate in this phenotype. The pump MexEF-OprN was discovered in 1997 and even if its contribution to antibiotic resistance among clinical strains of Pseudomonas aeruginosa had already been investigated, the molecular mechanisms giving rise to the pump overproduction has been poorly studied.

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