engleski

Tobramycin as a signal molecule in Pseudomonas aeruginosa

Aminoglycosides are clinically important antibiotics widely used to treat chronic bacterial infections in the lungs of cystic fibrosis (CF) patients. One of aminoglycosides is tobramycin (Tob), produced by the Streptomyces tenebrarius, and is commonly used for its effectiveness against opportunistic CF infections of Pseudomonas aeruginosa. Although antibiotics are thought to be small molecules having therapeutic activity in killing or inhibiting microbial growth, a few reports have shown that they can act as a small signaling molecules involved in cell-cell communication. P. aeruginosa utilizes cell-cell communication systems that rely on diffusible N-acylhomoserine lactone (AHL) signal molecules to monitor the size of population in a process known as quorum sensing (QS). In our studies we provide evidence that sub-inhibitory concentrations of Tob affect directly QS in an environmental isolate of P. aeruginosa. We determined the minimal inhibitory concentration of Tob in liquid and solid LB media for P. aeruginosa and also the highest sub-inhibitory concentration which does not affect growth, total protein levels and rates of translation. We have determined that the QS regulated swarming phenotype is affected by sub-inhibitory concentrations of tobramycin. In fact it was established that sub-inhibitory concentrations of Tob decrease the levels of one of the two AHL quorum sensing signalling molecules produced by P. aeruginosa. It was therefore concluded that tobramycin can act as a signal molecules and regulate QS in P. aeruginosa. Results of this study indicate that aminoglycosides can behave as signal molecules at sub-lethal concentrations. These results can be important in the design of appropriate antibiotic therapies of P. aeruginosa chronic infections in CF patients.

tobramycin; quorum sensing; methyltransferase NpmA; antibiotic resistance

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