Issue 43, 2022

Ultrasensitive detection of β-lactamase-associated drug-resistant bacteria using a novel mass-tagged probe-mediated cascaded signal amplification strategy

Abstract

The emergence and spread of drug-resistant bacteria (DRB) is a global health threat. Early and accurate detection of DRB is a critical step in the treatment of DRB infection. However, traditional assays for DRB detection are time-consuming and have inferior analytical sensitivity and quantification capability. Herein, a mass-tagged probe (MP-CMSA)-mediated enzyme- and light-assisted cascaded signal amplification strategy was developed for the ultrasensitive detection of β-lactamase (BLA), an enzyme closely associated with most DRB. Each MP-CMSA probe contained multiple poly(amidoamine) (PAMAM) dendrimer molecules immobilized on a streptavidin agarose bead via a BLA-cleavable linker, and each dendrimer was modified with multiple mass tags via a photo-cleavable linker. In BLA detection, BLA could cleave the BLA-cleavable linker, leading to dendrimers shedding from the MP-CMSA probe to achieve enzyme-assisted signal amplification. Then, each dendrimer can further release mass tags under UV light to achieve light-assisted signal amplification. After this cascaded signal amplification, the released mass tags were ultimately quantified by mass spectrometry. Consequently, the sensitivity of BLA detection can be significantly enhanced by four orders of magnitude with a detection limit of 50.0 fM. Finally, this approach was applied to the blood samples from patients with DRB. This platform provides a potential strategy for the sensitive, rapid and quantitative detection of DRB infection.

Graphical abstract: Ultrasensitive detection of β-lactamase-associated drug-resistant bacteria using a novel mass-tagged probe-mediated cascaded signal amplification strategy

Supplementary files

Article information

Article type
Edge Article
Submitted
16 Mar 2022
Accepted
11 Oct 2022
First published
25 Oct 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 12799-12807

Ultrasensitive detection of β-lactamase-associated drug-resistant bacteria using a novel mass-tagged probe-mediated cascaded signal amplification strategy

J. Zhu, Y. Bai, X. Chen, L. Hu, W. Zhang, C. Liu, H. Shao, J. Sun and Y. Chen, Chem. Sci., 2022, 13, 12799 DOI: 10.1039/D2SC01530G

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