Integrated Experimental and Computational Analyses Reveal Differential Metabolic Functionality in Antibiotic-Resistant Pseudomonas aeruginosa.
Cell Syst
; 8(1): 3-14.e3, 2019 01 23.
Article
em En
| MEDLINE
| ID: mdl-30611675
ABSTRACT
Metabolic adaptations accompanying the development of antibiotic resistance in bacteria remain poorly understood. To study this relationship, we profiled the growth of lab-evolved antibiotic-resistant lineages of the opportunistic pathogen Pseudomonas aeruginosa across 190 unique carbon sources. Our data revealed that the evolution of antibiotic resistance resulted in systems-level changes to growth dynamics and metabolic phenotype. A genome-scale metabolic network reconstruction of P. aeruginosa was paired with whole-genome sequencing data to predict genes contributing to observed changes in metabolism. We experimentally validated computational predictions to identify mutations in resistant P. aeruginosa affecting loss of catabolic function. Finally, we found a shared metabolic phenotype between lab-evolved P. aeruginosa and clinical isolates with similar mutational landscapes. Our results build upon previous knowledge of antibiotic-induced metabolic adaptation and provide a framework for the identification of metabolic limitations in antibiotic-resistant pathogens.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Genoma Bacteriano
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Biologia Computacional
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Farmacorresistência Bacteriana
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article