Rv3371, a triacylglycerol synthase promotes survival of Mycobacterium tuberculosis in the host through its contributions to redox homeostasis and propionate detoxification

IF 2.8 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2025-02-21 DOI:10.1016/j.tube.2025.102617

Rahul Kumar Maurya , Sarah Fatima , Swati Anand , Rajmani Raju , Suman Bharti , Shivangi Rastogi , Umamageswaran Venugopal , Amitava Sinha , Amit Singh , Manju Y. Krishnan

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引用次数: 0

Abstract

Triacylglycerol (TAG) is the major storage lipid of mycobacteria. Mycobacterium tuberculosis (Mtb) genome encodes 15 triacylglycerol synthases (Tgs), which are speculated to differ in substrate preference, suggesting specific physiological roles. In this study, we investigated the role of a Tgs, Rv3371, in the context of infection. Rv3371 knock-out (KO) Mtb was attenuated in mice, with corresponding poor fitness inside macrophages. The KO was more sensitive to free long-chain fatty acids, but was more tolerant to oxidative and nitrosative stresses. Enzyme kinetics of Rv3371 showed its preference for propionyl-CoA. Excess propionate in growth medium retarded the growth of the KO more significantly than the wild type and complemented mutant. This suggests an additional role of Rv3371 in reducing toxic levels of propionate in Mtb by synthesising propionyl TAG. Moreover, chemical inhibition of methylcitrate cycle caused a decrease in methyl-branched lipids in the KO. Overall, the results suggest a role of Rv3371 in Mtb survival in the host through its roles beyond TAG storage.

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.