The erythromycin polyketide compound TMC-154 stimulates ROS generation to exert antibacterial effects against Streptococcus pyogenes.

Autor: Yan YF; School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong 519041, China., Liu Y; School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong 519041, China., Liang H; School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong 519041, China., Cai L; Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Functional Molecules Analysis and Biotransformation Key Laboratory of Universities in Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China., Yang XY; School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong 519041, China. Electronic address: ouyangxiangyan@126.com., Yin TP; School of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong 519041, China. Electronic address: ytp@zmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2024 Feb 10; Vol. 292, pp. 105057. Date of Electronic Publication: 2023 Dec 01.
DOI: 10.1016/j.jprot.2023.105057
Abstrakt: The erythromycin polyketide compound TMC-154 is a secondary metabolite that is isolated from the rhizospheric fungus Clonostachys rogersoniana associated with Panax notoginseng, which possesses antibacterial activity. However, its antibacterial mechanism has not been investigated thus far. In this study, proteomics coupled with bioinformatics approaches was used to explore the antibacterial mechanism of TMC-154. KEGG pathway enrichment analysis indicated that eight signaling pathways were associated with TMC-154, including oxidative phosphorylation, cationic antimicrobial peptide (CAMP) resistance, benzoate degradation, heme acquisition systems, glycine/serine and threonine metabolism, beta-lactam resistance, ascorbate and aldarate metabolism, and phosphotransferase system (PTS). Cell biology experiments confirmed that TMC-154 could induce reactive oxygen species (ROS) generation in Streptococcus pyogenes; moreover, TMC-154-induced antibacterial effects could be blocked by the inhibition of ROS generation with the antioxidant N-acetyl L-cysteine. In addition, TMC-154 combined with ciprofloxacin or chloramphenicol had synergistic antibacterial effects. These findings indicate the potential of TMC-154 as a promising drug to treat S. pyogenes infections. SIGNIFICANCE: Streptococcus pyogenes is a nearly ubiquitous human pathogen that causes a variety of diseases ranging from mild pharyngitis and skin infection to fatal sepsis and toxic heat shock syndrome. With the increasing incidence of known antibiotic resistance, there is an urgent need to find novel drugs with good antibacterial activity against S. pyogenes. In this study, we found that TMC-154, a secondary metabolite from the fungus Clonostachys rogersoniana, inhibited the growth of various bacteria, including Staphylococcus aureus, S. pyogenes, Streptococcus mutans, Pseudomonas aeruginosa and Vibrio parahemolyticus. Proteomic analysis combined with cell biology experiments revealed that TMC-154 stimulated ROS generation to exert antibacterial effects against S. pyogenes. This study provides potential options for the treatment of S. pyogenes infections in the future.
Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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