1-benzyl-1,4-diazepane reduces the efflux of resistance-nodulation-cell division pumps inEscherichia coli

被引:7
作者
Casalone, Enrico [1 ]
Vignolini, Tiziano [2 ]
Braconi, Laura [3 ]
Gardini, Lucia [2 ,4 ]
Capitanio, Marco [2 ,5 ]
Pavone, Francesco S. [2 ,4 ,5 ]
Dei, Silvia [3 ]
Teodori, Elisabetta [3 ]
机构
[1] Univ Florence, Dept Biol, Via Madonna del Piano 6, I-50019 Sesto Fiorentino, Italy
[2] LENS European Lab Nonlinear Spect, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy
[3] Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Via U Schiff 6, I-650019 Sesto Fiorentino, Italy
[4] CNR, Natl Inst Opt, Largo Fermi 6, I-50125 Florence, Italy
[5] Univ Florence, Dept Phys & Astron, Via Sansone 1, I-50019 Sesto Fiorentino, Italy
基金
欧盟地平线“2020”;
关键词
AcrAB expression; E; coli; efflux-pump inhibitor; EPI; levofloxacin potentiation; MDR; membrane permeability; multidrug resistance; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; MULTIDRUG-RESISTANCE; MAR OPERON; ACRAB; 1-(1-NAPHTHYLMETHYL)-PIPERAZINE; SUSCEPTIBILITY; EXPRESSION; PHENOTYPE; GENES;
D O I
10.2217/fmb-2019-0296
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Aim:To investigate the action mechanism of 1-benzyl-1,4-diazepane (1-BD) as efflux pump inhibitor (EPI) inEscherichia colimutants: Delta acrABor overexpressing AcrAB and AcrEF efflux pumps.Materials & methods:Effect of 1-BD on: antibiotic potentiation, by microdilution method; membrane functionality, by fluorimetric assays; ethidium bromide accumulation, by fluorometric real-time efflux assay; AcrB expression, by quantitative photoactivated localization microscopy.Results:1-BD decreases the minimal inhibitory concentration of levofloxacin and other antibiotics and increase ethidium bromide accumulation inE. colioverexpressing efflux pumps but not in the Delta acrABstrain. 1-BD increases membranes permeability, without sensibly affecting inner membrane polarity and decreasesacrABtranscription.Conclusion:1-BD acts as an EPI inE. coliwith a mixed mechanism, different from that of major reference EPIs.
引用
收藏
页码:987 / 999
页数:13
相关论文
共 41 条
[1]   An alternative physiological role for the EmhABC efflux pump in Pseudomonas fluorescens cLP6a [J].
Adebusuyi, Abigail A. ;
Foght, Julia M. .
BMC MICROBIOLOGY, 2011, 11
[2]   Exposure to Sub-inhibitory Concentrations of the Chemosensitizer 1-(1-Naphthylmethyl)-Piperazine Creates Membrane Destabilization in Multi-Drug Resistant Klebsiella pneumoniae [J].
Anes, Joao ;
Sivasankaran, Sathesh K. ;
Muthappa, Dechamma M. ;
Fanning, Seamus ;
Srikumar, Shabarinath .
FRONTIERS IN MICROBIOLOGY, 2019, 10
[3]   The ins and outs of RND efflux pumps in Escherichia coli [J].
Anes, Joao ;
McCusker, Matthew P. ;
Fanning, Seamus ;
Martins, Marta .
FRONTIERS IN MICROBIOLOGY, 2015, 6
[4]   Selected arylpiperazines are capable of reversing multidrug resistance in Escherichia coli overexpressing RND efflux pumps [J].
Bohnert, HA ;
Kern, WV .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (02) :849-852
[5]  
Clinical and Laboratory Standard Institute (CLSI), 2010, M07A9 CLSI
[6]   SALICYLATE INDUCTION OF ANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI - ACTIVATION OF THE MAR OPERON AND A MAR-INDEPENDENT PATHWAY [J].
COHEN, SP ;
LEVY, SB ;
FOULDS, J ;
ROSNER, JL .
JOURNAL OF BACTERIOLOGY, 1993, 175 (24) :7856-7862
[7]   One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products [J].
Datsenko, KA ;
Wanner, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6640-6645
[8]   Structure of the AcrAB-TolC multidrug efflux pump [J].
Du, Dijun ;
Wang, Zhao ;
James, Nathan R. ;
Voss, Jarrod E. ;
Klimont, Ewa ;
Ohene-Agyei, Thelma ;
Venter, Henrietta ;
Chiu, Wah ;
Luisi, Ben F. .
NATURE, 2014, 509 (7501) :512-+
[9]   Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators [J].
Duraes, Fernando ;
Pinto, Madalena ;
Sousa, Emilia .
CURRENT MEDICINAL CHEMISTRY, 2018, 25 (42) :6030-6069
[10]  
EUCAST, 2000, CLIN MICROBIOL INFEC, V6, P570