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Mycobacterium tuberculosis H 2 S Functions as a Sink to Modulate Central Metabolism, Bioenergetics, and Drug Susceptibility.

التفاصيل البيبلوغرافية
العنوان: Mycobacterium tuberculosis H 2 S Functions as a Sink to Modulate Central Metabolism, Bioenergetics, and Drug Susceptibility.
المؤلفون: Kunota TTR; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa., Rahman MA; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa., Truebody BE; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa., Mackenzie JS; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa., Saini V; Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India., Lamprecht DA; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa., Adamson JH; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa., Sevalkar RR; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Lancaster JR Jr; Department of Pharmacology and Chemical Biology, Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Berney M; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10462, USA., Glasgow JN; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Steyn AJC; Africa Health Research Institute, University of KwaZulu Natal, Durban 4001, South Africa.; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.; Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
المصدر: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2021 Aug 13; Vol. 10 (8). Date of Electronic Publication: 2021 Aug 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101668981 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3921 (Print) Linking ISSN: 20763921 NLM ISO Abbreviation: Antioxidants (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, [2012]-
مستخلص: H 2 S is a potent gasotransmitter in eukaryotes and bacteria. Host-derived H 2 S has been shown to profoundly alter M. tuberculosis ( Mtb ) energy metabolism and growth. However, compelling evidence for endogenous production of H 2 S and its role in Mtb physiology is lacking. We show that multidrug-resistant and drug-susceptible clinical Mtb strains produce H 2 S, whereas H 2 S production in non-pathogenic M. smegmatis is barely detectable. We identified Rv3684 (Cds1) as an H 2 S-producing enzyme in Mtb and show that cds1 disruption reduces, but does not eliminate, H 2 S production, suggesting the involvement of multiple genes in H 2 S production. We identified endogenous H 2 S to be an effector molecule that maintains bioenergetic homeostasis by stimulating respiration primarily via cytochrome bd . Importantly, H 2 S plays a key role in central metabolism by modulating the balance between oxidative phosphorylation and glycolysis, and it functions as a sink to recycle sulfur atoms back to cysteine to maintain sulfur homeostasis. Lastly, Mtb -generated H 2 S regulates redox homeostasis and susceptibility to anti-TB drugs clofazimine and rifampicin. These findings reveal previously unknown facets of Mtb physiology and have implications for routine laboratory culturing, understanding drug susceptibility, and improved diagnostics.
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معلومات مُعتمدة: R01 AI134810 United States AI NIAID NIH HHS; R01AI137043 United States NH NIH HHS; R01AI134810 United States NH NIH HHS; R33AI138280 United States NH NIH HHS
فهرسة مساهمة: Keywords: Agilent Seahorse XFe96; CytBD; H2S; Mycobacterium tuberculosis; Rv3684; bioenergetics; cysteine; energy metabolism; ergothioneine; metabolomics; mycothiol; redox homeostasis; respiration
تواريخ الأحداث: Date Created: 20210827 Latest Revision: 20231206
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC8389258
DOI: 10.3390/antiox10081285
PMID: 34439535
قاعدة البيانات: MEDLINE
الوصف
تدمد:2076-3921
DOI:10.3390/antiox10081285