Use of bacterial beta-lactamase for in vitro diagnostics and in vivo imaging, diagnostics and therapeutics

摘要

Provided herein are methods for detecting, quantifying, differentiating, diagnosing and imaging pathogenic bacteria or condition associated therewith using substrates for bacterial enzymes. Fluorescent, luminescent or colorimetric signals emitted by substrates or enzyme products in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring a signal emitted from the substrates or products in the presence and absence of the potential therapeutic agent and a diagnostic method for detecting a mycobacterial infection in a subject by contacting biological samples with a substrate and imaging for signals emitted from a mycobacterial beta-lactamase product. Also provided are fluorogenic substrates or substrates comprising a colored dye or a chemical reagent effective to induce a color or pH change.

主权项

1. A method for detecting a pathogenic Mycobacteria in real time in a subject or a biological sample, comprising:
introducing into a subject or contacting a biological sample therefrom or obtained from a surface with a fluorogenic substrate for a beta-lactamase of the pathogenic Mycobacteria, wherein the fluorogenic substrate is selected from the group consisting of CNIR800-3, XHX2-81, XHX2-91, XHX3-1, XHX3-26 and XHX3-32; imaging the subject or sample for a product from beta-lactamase activity on the substrate; and acquiring signals in real time at a wavelength emitted by the beta-lactamase product, thereby detecting the pathogenic Mycobacteria in the subject or the sample.