Efflux Pump Overexpression Profiling in Acinetobacter baumannii and Study of New 1-(1-Naphthylmethyl)-Piperazine Analogs as Potential Efflux Inhibitors.
Antimicrob Agents Chemother
; 65(9): e0071021, 2021 08 17.
Article
em En
| MEDLINE
| ID: mdl-34097483
ABSTRACT
Overexpression of efflux pumps extruding antibiotics currently used for the treatment of Acinetobacter baumannii infections has been described as an important mechanism causing antibiotic resistance. The first aim of this work was to phenotypically evaluate the overexpression of efflux pumps on a collection of 124 ciprofloxacin-resistant A. baumannii strains. An overexpression of genes encoding one or more efflux pumps was obtained for 19 out of the 34 strains with a positive phenotypic efflux (56%). The most frequent genes overexpressed were those belonging to the RND family, with adeJ being the most prevalent (50%). Interestingly, efflux pump genes coding for MATE and MFS families were also overexpressed quite frequently abeM (32%) and abaQ (26%). The second aim was to synthesize 1-(1-naphthylmethyl)-piperazine analogs as potential new efflux pump inhibitors and biologically evaluate them against strains with a positive phenotypic efflux. Quinoline and pyridine analogs were found to be more effective than their parent compound, 1-(1-naphthyl methyl)-piperazine. Stereochemistry also played an important part in the inhibitory activity, as quinoline derivative (R)-3a was identified as being the most effective and less cytotoxic. Its inhibitory activity was also correlated with the number of efflux pumps expressed by a strain. The results obtained in this work suggest that quinoline analogs of 1-(1-naphthylmethyl)-piperazine are promising leads in the development of new anti-Acinetobacter baumannii therapeutic alternatives in combination with antibiotics for which an efflux-mediated resistance is suspected.
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Base de dados:
MEDLINE
Assunto principal:
Acinetobacter baumannii
Limite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França