High-throughput fluorescent screening of ß-lactamase inhibitors to improve antibiotic treatment strategies for tuberculosis.
Biosens Bioelectron
; 216: 114606, 2022 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-35952435
ABSTRACT
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which is a major threat to global public health. Currently, ß-lactam antibiotics are rarely used in the treatment of TB, since Mtb naturally expresses ß-lactamase (Blac) which renders Mtb resistant to such antibiotics due to ß-lactam cleavage. Fortunately, antibiotic resistance can be overcome when ß-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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Técnicas Biossensoriais
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Mycobacterium tuberculosis
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Biosens Bioelectron
Ano de publicação:
2022
Tipo de documento:
Article