Evolution of the Pseudomonas aeruginosa aminoglycoside mutational resistome in vitro and in the cystic fibrosis setting.

López-Causapé C¹, Rubio R², Cabot G², Oliver A².

¹ Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca, Spain. carla.lopez@ssib.es.

² Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca, Spain.

Abstract

Inhaled administration of high doses of aminoglycosides is a key maintenance treatment of Pseudomonas aeruginosa chronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of step-wise high-level tobramycin resistance development in vitro and compared the results with those of isogenic pairs of susceptible-resistant clinical isolates. Resistance development correlated with fusA1 mutations in vitro and in vivo pmrB mutations, conferring polymyxin resistance, were also frequently selected in vitro In contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed in in vitro evolution experiments.

Antimicrobial Agents and Chemotherapy 2018. doi: 10.1128/AAC.02583-17.

Link to Pubmed