Coordinate overexpression of two RND efflux systems, ParXY and TtgABC, is responsible for multidrug resistance in Pseudomonas putida.
Environ Microbiol
; 22(12): 5222-5231, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-32840000
ABSTRACT
Resistance Nodulation cell Division (RND) efflux pumps are known to contribute to the tolerance of Pseudomonas putida to aromatic hydrocarbons, but their role in antibiotic resistance has not been fully elucidated. In this study, two types of single-step multidrug-resistant (MDR) mutants were selected in vitro from reference strain KT2440. Mutants of the first type were more resistant to fluoroquinolones and ß-lactams except imipenem, and overproduced the efflux system TtgABC as a result of mutations occurring in regulator TtgR. In addition to TtgABC, mutants of the second type such as HPG-5 were found to upregulate a novel RND pump, dubbed ParXY/TtgC, which accommodates cefepim, fluoroquinolones and aminoglycosides. As demonstrated by gene deletion experiments, TtgABC and ParXY/TtgC are both under the positive control of a two-component system, PpeRS. Whole-genome sequence analyses revealed that mutant HPG-5 harbours a mutation inactivating the gene (sucD) of succinyl-CoA synthetase, an enzyme of the tricarboxylic cycle. Disruption of sucD in strain KT2440 reproduced the resistance phenotype of HPG-5, and activated the glyoxylate shunt. Finally, identification of two MDR clinical strains of P. putida that jointly overexpress TtgABC and ParXY/TtgC, of which one is a sucD mutant, highlights the role of these efflux systems as determinants of antibiotic resistance.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
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Regulación Bacteriana de la Expresión Génica
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Pseudomonas putida
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Farmacorresistencia Bacteriana Múltiple
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Antibacterianos
Idioma:
En
Revista:
Environ Microbiol
Asunto de la revista:
MICROBIOLOGIA
/
SAUDE AMBIENTAL
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia