Functional Evolution and Therapeutic Potential of Toxin-antitoxin Systems in Mycobacterium tuberculosis and Bordetella pertussis
10.13865/j.cnki.cjbmb.2025.09.1325
- VernacularTitle:结核分枝杆菌与百日咳鲍特菌毒素-抗毒素系统的功能进化及治疗潜力
- Author:
Abuduka-Dir ABULIMITI
1
;
Pei-Bo LI
;
Jian-Ping XIE
Author Information
1. 西南大学生命科学学院现代生物医药研究所,重庆 400715
- Publication Type:Journal Article
- Keywords:
toxin-antitoxin(TA)systems;
persisters;
immune evasion;
anti-infection targets;
vaccine design
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(10):1457-1466
- CountryChina
- Language:Chinese
-
Abstract:
Toxin-antitoxin(TA)systems serve as central hubs of bacterial adaptive regulation and play critical roles in the pathogenesis of Mycobacterium tuberculosis(M.tb)and Bordetella pertussis(B.per-tussis).This review summarizes the functional evolution and therapeutic potential of TA systems in M.tb and B.pertussis.It systematically outlines the molecular mechanisms and pathogenic functions of TA sys-tems in these two pathogens.M.tb relies on type Ⅱ TA systems(e.g.,VapBC,MazEF)to drive persis-ter formation and antibiotic tolerance through toxin-mediated ribonuclease activity that cleaves host nucle-ic acids or DarT/DarG-mediated DNA modification.In contrast,B.pertussis utilizes a unique tempera-ture-sensing PhtA/PhtB system to release adenylate cyclase toxin,which targets the host cAMP signaling pathway to achieve immune evasion.Both pathogens employ TA toxins to suppress host defenses-such as VapC cleaving tRNA and RelE degrading NF-κB components.Their high-frequency mutation sites(e.g.,the VapC47-Ser46Leu mutation frequency＞50 000 in M.tuberculosis)reveal strong positive selec-tion pressure,closely associated with persister phenotypes and virulence evolution.This review further discusses therapeutic strategies,including small-molecule inhibitors targeting toxin-antitoxin interactions,TA-deletion attenuated vaccines,and antitoxin-based immunization approaches.Finally,it highlights the need for future research to elucidate TA-host interaction networks and develop nanocarrier delivery tech-nologies to advance breakthroughs in precision therapy for tuberculosis and pertussis.
