Aminoglycoside resistance 16s rRNA methyltransferases: Mechanism of action, biological cost and interference with intrinsic methylations
Belén Gutiérrez Soriano defended the PhD Thesis at the Faculty of Veterinary Medicine of the Complutense University of Madrid
June 23rd, 2014
In this work we strive to elucidate this rapidly disseminating resistance mechanism as it is emerging in more and more bacterial pathogens globally. On the one hand we have studied the mechanism of action, biological cost and the relationship between acquired methylations and adjacent intrinsic methylations present in the bacterial ribosome. Furthermore, we have also studied the post-transcriptional methylations of both endogenous and acquired methylases in the aminoglycoside target-site within the rRNAs of Pseudomonas aeruginosa. This microbe was chosen, as aminoglycosides are the first choice antimicrobial for the treatment of infections caused by this pathogen, specifically, tobramycin in patients suffering from cystic fibrosis. The fact that this particular pathogen has acquired a resistance conferring methyltransferase significantly complicates treatment. For this reason, thoroughly elucidating the targets of the antibiotics in the rRNAs of this pathogen is a fundamental step in order to alleviate this concern as soon as possible. Finally, at the beginning of this doctoral thesis in the process of looking for emerging aminoglycoside resistant mechanisms, we found a clinical isolate of Samonella Bredeney with an unusual antimicrobial resistance pattern, which included aminoglycosides, β-lactams, chloramphenicol and tetraciclines. In orther to study the coexistence of different antimicrobial resistance genes, their genetic environment and mechanisms of acquisition, we decided to characterize the genetic molecular basis of that strain
