B-lactamase remodeling and evolution of collateral resistance in hypermutator Pseudomonas aeruginosa upon long-term antibiotic therapy

COLQUE CA; TOMATIS PE; ALBARRACÍN ORIO A; DOTTA G; MORENO D; HEDEMANN LG; HICKMAN RA; SOMMER LM; FELIZIANI S; MOYANO AJ; BONOMO RA; KROGH JOHANSEN H; MOLIN S; VILA AJ; SMANIA AM

bioRxiv

Cold Spring Harbor

Año: 2021

acteria are endowed with a unique ability to adapt to challenging environments. The evolution of bacterial populations during chronic infections involves a large diversity of adaptive mechanisms that cannot always be reproduced upon controlled laboratory conditions. This creates a gap between the phenotypical description and the underlying biochemical processes that drive that phenotype. Herein, we address the complexity of the bacterial adaptive response to antibiotic selective pressures by studying the in-patient evolution of a broad diversity of β-lactam resistant Pseudomonas aeruginosa hypermutator clones. By using mutational and ultra-deep amplicon sequencing analysis, we analyzed multiple generations of a P. aeruginosa hypermutator strain persisting for more than 26 years of chronic infection in the airways of a cystic fibrosis patient. We identify the accumulation of multiple alterations targeting the chromosomally encoded class C β-lactamase (blaPDC), providing struc