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Actividad Científica

31 - jul. - 2017
Antibiotic resistance in the focus of IDIVAL’s researchers

IDIVAL's Clinical and Molecular Microbiology group has participated in a study about the evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

Pseudomonas aeruginosa chronic respiratory infection (CRI) is the main driver of morbidity and mortality in patients suffering from cystic fibrosis (CF). The CF respiratory tract is a dynamic, heterogeneous, hostile, stressful and very challenging scenario for invading bacteria, but P. aeruginosa populations can overcome all these challenges and chronically persist in the CF lungs. Mechanisms underlying early acquisition of P. aeruginosa infection and the eventual establishment of CRI are complex and, many factors, related to the patient, the environment and the microorganism, are involved.

Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of P. aeruginosa CF clones and it is correlation with resistance phenotypes, which might be useful for guiding new diagnostic tools and therapeutic strategies in CRI.

Reference: López-Causapé C, Sommer LM, Cabot G, Rubio R, Ocampo-Sosa AA, Johansen HK, Figuerola J, Cantón R, Kidd TJ, Molin S, Oliver A. Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone. Sci Rep. 2017 Jul 17;7(1):5555.





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