Abstract
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which is a major threat to global public health. Currently, β-lactam antibiotics are rarely used in the treatment of TB, since Mtb naturally expresses β-lactamase (Blac) which renders Mtb resistant to such antibiotics due to β-lactam cleavage. Fortunately, antibiotic resistance can be overcome when β-lactam antibiotics are combined with a Blac inhibitor. With the current research, a near-infrared fluorescent probe LXMB was developed for the real-time detection and imaging of endogenous Blac activity in Mtb. Furthermore, a high-throughput screening platform was established using LXMB to screen Blac inhibitors from herbal medicines. Guided by the visual bioassay, Tannic acid was isolated from Galla Chinensis as a potential Blac inhibitor and was further evaluated in combination with several β-lactam antibiotics which resulted in an enhanced inhibitory effect toward M. tuberculosis H37Ra. Finally, LXMB was used to label live M. tuberculosis H37Ra phagocytosed within macrophages. Consequently, LXMB was a useful fluorescent tool to explore the mechanism of drug resistance based on Blac and can assist in the development of new tuberculosis treatments.
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