气候变化领域集成服务门户(CCPortal): Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity

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DOI	10.1073/pnas.2024571118
	Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity
	Gouzy A.; Healy C.; Black K.A.; Rhee K.Y.; Ehrt S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:32
英文摘要	Acidic pH arrests the growth of Mycobacterium tuberculosis in vitro (pH < 5.8) and is thought to significantly contribute to the ability of macrophages to control M. tuberculosis replication. However, this pathogen has been shown to survive and even slowly replicate within macrophage phagolysosomes (pH 4.5 to 5) [M. S. Gomes et al., Infect. Immun. 67, 3199-3206 (1999)] [S. Levitte et al., Cell Host Microbe 20, 250-258 (2016)]. Here, we demonstrate that M. tuberculosis can grow at acidic pH, as low as pH 4.5, in the presence of host-relevant lipids. We show that lack of phosphoenolpyruvate carboxykinase and isocitrate lyase, two enzymes necessary for lipid assimilation, is cidal to M. tuberculosis in the presence of oleic acid at acidic pH. Metabolomic analysis revealed that M. tuberculosis responds to acidic pH by altering its metabolism to preferentially assimilate lipids such as oleic acid over carbohydrates such as glycerol. We show that the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is impaired in acid-exposed M. tuberculosis likely contributing to a reduction in glycolytic flux. The generation of endogenous reactive oxygen species at acidic pH is consistent with the inhibition of GAPDH, an enzyme well-known to be sensitive to oxidation. This work shows that M. tuberculosis alters its carbon diet in response to pH and provides a greater understanding of the physiology of this pathogen during acid stress. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acid stress; Glyceraldehyde-3-phosphate dehydrogenase; Lipid catabolism; Metabolism; Mycobacterium tuberculosis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238449
作者单位	Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, United States; School of Medicine, Trinity College Dublin, Dublin 2, Ireland
推荐引用方式 GB/T 7714	Gouzy A.,Healy C.,Black K.A.,et al. Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity[J],2021,118(32).
APA	Gouzy A.,Healy C.,Black K.A.,Rhee K.Y.,&Ehrt S..(2021).Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity.Proceedings of the National Academy of Sciences of the United States of America,118(32).
MLA	Gouzy A.,et al."Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity".Proceedings of the National Academy of Sciences of the United States of America 118.32(2021).