Development of a whole-cell biosensor for β-lactamase inhibitor discovery

被引:2
作者
Jeffs, Mitchell A. [1 ]
Gray, Rachel A. V. [1 ]
Sheth, Prameet M. [1 ,2 ]
Lohans, Christopher T. [1 ]
机构
[1] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON, Canada
[2] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada
关键词
IN-VITRO ACTIVITY; PSEUDOMONAS-AERUGINOSA; CARBAPENEMASE; NXL104; AMPR; COMBINATIONS; CEFTAZIDIME; RESISTANCE;
D O I
10.1039/d3cc03583b
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The production of beta-lactamases by bacterial pathogens endangers antimicrobial therapy, and new inhibitors for beta-lactamases are urgently needed. We report the development of a luminescent-based biosensor that quantifies beta-lactamase inhibition in a cellular context, based on the activation of transcriptional factor AmpR following the exposure of bacterial cells to beta-lactams. This rapid method can account for factors like membrane permeability and can be employed to identify new beta-lactamase inhibitors. We developed a whole-cell biosensor that quantifies beta-lactamase inhibition in a cellular context. This assay accounts for factors such as membrane permeability and can be used to identify novel beta-lactamase inhibitors.
引用
收藏
页码:12707 / 12710
页数:4
相关论文
共 38 条
[1]   Weakening effect of cell permeabilizers on gram-negative bacteria causing biodeterioration [J].
Alakomi, H. -L. ;
Paananen, A. ;
Suihko, M. -L. ;
Helander, I. M. ;
Saarela, M. .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2006, 72 (07) :4695-4703
[2]   CENTA as a chromogenic substrate for studying β-lactamases [J].
Bebrone, C ;
Moali, C ;
Mahy, F ;
Rival, S ;
Docquier, JD ;
Rossolini, GM ;
Fastrez, J ;
Pratt, RF ;
Frère, JM ;
Galleni, M .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (06) :1868-1871
[3]   Carbapenemase-Producing Organisms: A Global Scourge [J].
Bonomo, Robert A. ;
Burd, Eileen M. ;
Conly, John ;
Limbago, Brandi M. ;
Poirel, Laurent ;
Segre, Julie A. ;
Westblade, Lars F. .
CLINICAL INFECTIOUS DISEASES, 2018, 66 (08) :1290-1297
[4]   Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers [J].
Brem, Juergen ;
van Berkel, Sander S. ;
Zollman, David ;
Lee, Sook Y. ;
Gileadi, Opher ;
McHugh, Peter J. ;
Walsh, Timothy R. ;
McDonough, Michael A. ;
Schofield, Christopher J. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2016, 60 (01) :142-150
[5]   BLIP-II Is a Highly Potent Inhibitor of Klebsiella pneumoniae Carbapenemase (KPC-2) [J].
Brown, Nicholas G. ;
Chow, Dar-Chone ;
Palzkill, Timothy .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (07) :3398-3401
[6]   Epidemiology of β-Lactamase-Producing Pathogens [J].
Bush, Karen ;
Bradford, Patricia A. .
CLINICAL MICROBIOLOGY REVIEWS, 2020, 33 (02)
[7]   β-Lactams and β-Lactamase Inhibitors: An Overview [J].
Bush, Karen ;
Bradford, Patricia A. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2016, 6 (08)
[8]   Distinct Roles of Outer Membrane Porins in Antibiotic Resistance and Membrane Integrity in Escherichia coli [J].
Choi, Umji ;
Lee, Chang-Ro .
FRONTIERS IN MICROBIOLOGY, 2019, 10
[9]   An evaluation of the in vitro activity of piperacillin/tazobactam [J].
Daley, D ;
Mulgrave, L ;
Munro, R ;
Neville, S ;
Smith, H ;
Dimech, W .
PATHOLOGY, 1996, 28 (02) :167-172
[10]   Evaluation of the inoculum effect of new antibiotics against carbapenem-resistant enterobacterales [J].
Danjean, Maxime ;
Hobson, Claire Amaris ;
Gits-Muselli, Maud ;
Courroux, Celine ;
Monjault, Audrey ;
Bonacorsi, Stephane ;
Birgy, Andre .
CLINICAL MICROBIOLOGY AND INFECTION, 2022, 28 (11) :1503.e1-1503.e3