Journal
SCIENCE CHINA-MATERIALS
Volume 65, Issue 1, Pages 237-245Publisher
SCIENCE PRESS
DOI: 10.1007/s40843-021-1735-0
Keywords
Gram-positive bacteria; selective inactivation; photothermal agent; metabolic labelling; wound infection
Categories
Funding
- National Natural Science Foundation of China [52003222, 21875189]
- Ningbo Natural Science Foundation [202003N4064]
- Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0752]
- Department of Science AMP
- Technology of Shaanxi Province [2020GXLH-Z-013]
- Fundamental Research Funds for the Central Universities
- Northwestern Polytechnical University [2020GXLH-Z-013]
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Bacterial infections are a serious threat to human health, especially those caused by common Gram-positive bacteria. Photothermal therapy (PTT) has shown potential as a universal antimicrobial technique without inducing drug resistance, but its unspecific killing capability and side effects hinder practical applications. A metabolic engineering strategy using a bioorthogonal photothermal agent was proposed to selectively inactivate Gram-positive bacteria by pre-metabolizing with 3-azido-D-alanine, demonstrating efficient eradication in vitro and in a mouse model. This strategy could lead to the development of precise antibacterial candidates for preclinical applications.
Bacterial infections are grave threats to human health, particularly those caused by the most common Gram-positive bacteria. The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance. As a universal antimicrobial technique unapt to induce drug resistance, photothermal therapy (PTT) is attracting extensive attention in recent years. However, its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications. Herein, we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT. A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzo-cyclooctyne (IR780-DBCO). Upon pre-metabolizing with 3-azido-D-alanine, Gram-positive bacteria rather than Gram-negative ones, such as Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (VRE), could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry. Thereafter, they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro. Moreover, superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model. This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.
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