{"title":"甲基乙二醛解毒在结核分枝杆菌适应性和发病机制中的作用。","authors":"Haiqi Chen, Abulimiti Abudukadier, Qi'ao Zhang, Peibo Li, Jianping Xie","doi":"10.1016/j.micpath.2025.107948","DOIUrl":null,"url":null,"abstract":"<p><p>Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), constitutes a major global health challenge. The pathogenesis of Mtb can be largely attributed to its sophisticated survival strategies within host macrophages. Methylglyoxal (MGO), a ubiquitous reactive dicarbonyl metabolite that spontaneously reacts with biopolymers forming advanced glycation end products (AGEs), togethers with reactive oxygen species (ROS) damage cellular events. The glyoxalase system serves as the primary metabolic pathway for MGO detoxification, mitigating carbonyl stress induced by excess MGO. The mycobacterial glyoxalase system likely functions as a vital defense mechanism against glycation and oxidative stress generated during pathogenic infection. Although extensive research has been conducted on the host glyoxalase system against diabetes, little is known about the mechanisms behind MGO detoxification in Mtb. This review aims at exploring the impact of MGO and its product AGEs on TB treatment and discussing the key molecular components, functions, and regulatory roles of the glyoxalase system in Mtb. Finally, we propose the utilization of mycobacterial glyoxalases as therapeutic targets for the development of anti-tuberculosis drugs.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107948"},"PeriodicalIF":3.5000,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The role of methylglyoxal detoxification in Mycobacterium tuberculosis fitness and pathogenesis.\",\"authors\":\"Haiqi Chen, Abulimiti Abudukadier, Qi'ao Zhang, Peibo Li, Jianping Xie\",\"doi\":\"10.1016/j.micpath.2025.107948\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), constitutes a major global health challenge. The pathogenesis of Mtb can be largely attributed to its sophisticated survival strategies within host macrophages. Methylglyoxal (MGO), a ubiquitous reactive dicarbonyl metabolite that spontaneously reacts with biopolymers forming advanced glycation end products (AGEs), togethers with reactive oxygen species (ROS) damage cellular events. The glyoxalase system serves as the primary metabolic pathway for MGO detoxification, mitigating carbonyl stress induced by excess MGO. The mycobacterial glyoxalase system likely functions as a vital defense mechanism against glycation and oxidative stress generated during pathogenic infection. Although extensive research has been conducted on the host glyoxalase system against diabetes, little is known about the mechanisms behind MGO detoxification in Mtb. This review aims at exploring the impact of MGO and its product AGEs on TB treatment and discussing the key molecular components, functions, and regulatory roles of the glyoxalase system in Mtb. Finally, we propose the utilization of mycobacterial glyoxalases as therapeutic targets for the development of anti-tuberculosis drugs.</p>\",\"PeriodicalId\":18599,\"journal\":{\"name\":\"Microbial pathogenesis\",\"volume\":\" \",\"pages\":\"107948\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbial pathogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.micpath.2025.107948\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbial pathogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.micpath.2025.107948","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/5 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
The role of methylglyoxal detoxification in Mycobacterium tuberculosis fitness and pathogenesis.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), constitutes a major global health challenge. The pathogenesis of Mtb can be largely attributed to its sophisticated survival strategies within host macrophages. Methylglyoxal (MGO), a ubiquitous reactive dicarbonyl metabolite that spontaneously reacts with biopolymers forming advanced glycation end products (AGEs), togethers with reactive oxygen species (ROS) damage cellular events. The glyoxalase system serves as the primary metabolic pathway for MGO detoxification, mitigating carbonyl stress induced by excess MGO. The mycobacterial glyoxalase system likely functions as a vital defense mechanism against glycation and oxidative stress generated during pathogenic infection. Although extensive research has been conducted on the host glyoxalase system against diabetes, little is known about the mechanisms behind MGO detoxification in Mtb. This review aims at exploring the impact of MGO and its product AGEs on TB treatment and discussing the key molecular components, functions, and regulatory roles of the glyoxalase system in Mtb. Finally, we propose the utilization of mycobacterial glyoxalases as therapeutic targets for the development of anti-tuberculosis drugs.
期刊介绍:
Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports.
Research Areas Include:
-Pathogenesis
-Virulence factors
-Host susceptibility or resistance
-Immune mechanisms
-Identification, cloning and sequencing of relevant genes
-Genetic studies
-Viruses, prokaryotic organisms and protozoa
-Microbiota
-Systems biology related to infectious diseases
-Targets for vaccine design (pre-clinical studies)