Detection of Carbapenemase‐Producing Organisms with a Carbapenem‐Based Fluorogenic Probe

Mao, Wuyu; Xia, Lingying; Xie, Hexin

doi:10.1002/anie.201612495

Cited by 62 publications

(46 citation statements)

References 44 publications

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“…Recent developments in probe design for the detection of carbapenemase activity have included an example based on coumarin as a fluorescent dye, with modified cephalosporin as a triggering substrate (Figure A) . In addition, an unprecedented enamine BODIPY switch, cleverly introduced by Xie's group, enabled the development of a highly efficient fluorogenic probe for the selective detection of carbapenemase activity over other β‐lactamase activity (Figure B, (1)) …”

Section: Resultsmentioning

confidence: 99%

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Das

Ihssen²,

Wick³

et al. 2020

Chemistry A European J

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Carbapenemase‐producing organisms (CPOs) pose a severe threat to antibacterial treatment due to the acquisition of antibiotic resistance. This resistance can be largely attributed to the antibiotic‐hydrolyzing enzymes that the bacteria produce. Current carbapenem “wonder drugs”, such as doripenem, ertapenem, meropenem, imipenem, and so on, are resistant to regular β‐lactamases, but susceptible to carbapenemases. Even worse, extended exposure of bacteria to these drugs accelerates the spread of resistance genes. In order to preserve the clinical efficacy of antibacterial treatment, carbapenem drugs should be carefully regulated and deployed only in cases of a CPO infection. Early diagnosis is therefore of paramount importance. Herein, we report the design, synthesis, and activity of the first carbapenemase‐sensitive chemiluminescent probe, CPCL, which may be used to monitor CPO activity. The design of our probe enables enzymatic cleavage of the carbapenem core, which is followed by a facile 1,8‐elimination process and the emission of green light through rapid chemical excitation. We have demonstrated the ability of the probe to detect a number of clinically relevant carbapenemases and the successful identification of CPO present in bacterial cultures, such as those used for clinical diagnosis. We believe that our use of “turn‐on” chemiluminescence activation will find significant application in future diagnostic assays and improve antibacterial treatment.

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Section: Resultsmentioning

confidence: 99%

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Das

Ihssen²,

Wick³

et al. 2020

Chemistry A European J

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“…The synthesis of CPC‐1 is outlined in Scheme . Readily available compound 1 was first oxidized to 2‐formyl carbapenem 2 , followed by THF–borane‐mediated reduction, to yield key intermediate 2‐hydroxymethylcarbapenem 3 . This compound was then transformed into carbonate intermediate 4 , and a palladium‐catalyzed reaction was utilized to introduce umbelliferone.…”

Section: Methodsmentioning

confidence: 90%

“…reported a number of carbapenemase‐selective fluorescent probes on the basis of stereochemically altered cephalosporin . Recently, with the core structure of carbapenem antibiotics as an enzymatic recognition moiety, we disclosed a boron dipyrromethene (BODIPY)‐based fluorescent sensor that exhibited excellent specificity to carbapenemases . Herein, following our continuing interest on this topic, [11l, 11 ° , 13] we describe a carbapenem‐based fluorescent substrate that is highly specific to MBLs.…”

Section: Methodsmentioning

confidence: 99%

“…Determination of LOD : The recombinant MBLs (VIM‐27, IMP‐1, NDM‐1) were obtained as previously reported . CPC‐1 (10 μ m ) and a series of concentrations (ranging from 0.02 to 3 n m ) of VIM‐27, IMP‐1, and NDM‐1, in PBS (pH 7.4 with 0.1 % 3‐[(3‐cholamidopropyl)dimethylammonium]‐1‐propanesulfonate (CHAPS) as a surfactant; total volume: 100 μL) were added to a 96‐well black plate.…”

Section: Methodsmentioning

confidence: 99%

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A Carbapenem‐Based Off–On Fluorescent Probe for Specific Detection of Metallo‐β‐Lactamase Activities

et al. 2018

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Metallo-β-lactamase is one of the major clinical threats because this β-lactam-hydrolyzing enzyme confers significant resistance to most β-lactam antibiotics, including carbapenems, among bacterial pathogens. Reported herein is a novel fluorogenic sensor for the specific detection of metallo-β-lactamase activities. This carbapenem-based reagent exhibits excellent selectivity to metallo-β-lactamase over other serine-β-lactamases, including serine carbapenemases. The usefulness of this probe was further demonstrated in the rapid identification of metallo-β-lactamase-expressing pathogenic bacteria.

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“…Enzymatic kinetics : Recombinant CTX‐M‐9, NDM‐1, KPC‐3, VIM‐27, IMP‐1, and TEM‐1 blas were expressed and purified as previously described . Kinetic experiments were conducted at 22 °C in PBS (pH 7.4 with 0.1 % 3‐[(3‐cholamidopropyl)dimethylammonium]‐1‐propanesulfonate (CHAPS) as a surfactant).…”

Section: Figurementioning

confidence: 99%

Specific Detection of Extended‐Spectrum β‐Lactamase Activities with a Ratiometric Fluorescent Probe

et al. 2017

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The dissemination of antimicrobial resistance around the world is one of the biggest threats to global public health. The acquisition and expression of extended-spectrum β-lactamases (ESBLs) in pathogenic bacterial are mainly responsible for bacterial resistance to third-generation cephalosporins. Reported herein is a ratiometric fluorescent probe for the detection of the activity of ESBLs. This imaging reagent adopts the core structure of cefotaxime as an enzymatic recognition moiety, and exhibits excellent selectivity to ESBLs over other β-lactamases. The specific activation of this sensor by ESBLs can lead to over 2500-fold changes in the fluorescent ratio, which is independent of the concentration of the probe and environmental conditions. Further experiments have demonstrated that this ratiometric fluorescent probe can distinguish bacteria with extended-spectrum antibiotic resistance from a group of clinically important pathogens within a short period of time.

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Detection of Carbapenemase‐Producing Organisms with a Carbapenem‐Based Fluorogenic Probe

Cited by 62 publications

References 44 publications

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

A Carbapenem‐Based Off–On Fluorescent Probe for Specific Detection of Metallo‐β‐Lactamase Activities

Specific Detection of Extended‐Spectrum β‐Lactamase Activities with a Ratiometric Fluorescent Probe

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