气候变化领域集成服务门户(CCPortal): Staphylococcus aureus adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement

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DOI	10.1073/pnas.2022720118
	Staphylococcus aureus adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement
	Teoh W.P.; Chen X.; Laczkovich I.; Alonzo F.; III
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	During infection, pathogenic microbes adapt to the nutritional milieu of the host through metabolic reprogramming and nutrient scavenging. For the bacterial pathogen Staphylococcus aureus, virulence in diverse infection sites is driven by the ability to scavenge myriad host nutrients, including lipoic acid, a cofactor required for the function of several critical metabolic enzyme complexes. S. aureus shuttles lipoic acid between these enzyme complexes via the amidotransferase, LipL. Here, we find that acquisition of lipoic acid, or its attachment via LipL to enzyme complexes required for the generation of acetyl-CoA and branched-chain fatty acids, is essential for bacteremia, yet dispensable for skin infection in mice. A lipL mutant is auxotrophic for carboxylic acid precursors required for synthesis of branched-chain fatty acids, an essential component of staphylococcal membrane lipids and the agent of membrane fluidity. However, the skin is devoid of branched-chain fatty acids. We showed that S. aureus instead scavenges host-derived unsaturated fatty acids from the skin using the secreted lipase, Geh, and the unsaturated fatty acid–binding protein, FakB2. Moreover, murine infections demonstrated the relevance of host lipid assimilation to staphylococcal survival. Altogether, these studies provide insight into an adaptive trait that bypasses de novo lipid synthesis to facilitate S. aureus persistence during superficial infection. The findings also reinforce the inherent challenges associated with targeting bacterial lipogenesis as an antibacterial strategy and support simultaneous inhibition of host fatty acid salvage during treatment. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Branched-chain fatty acid; Lipoic acid; Membrane; Staphylococcus aureus; Virulence
语种	英语
scopus关键词	branched chain amino acid; tetrahydrolipstatin; thioctic acid; triacylglycerol lipase; unsaturated fatty acid; amino acid synthesis; animal experiment; animal model; animal tissue; Article; auxotrophy; bacterial colonization; bacterial load; bacterial survival; controlled study; fatty acid synthesis; in vitro study; lipogenesis; lipoylation; mouse; nonhuman; priority journal; skin infection; soft tissue infection; Staphylococcus aureus; wild type
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/180073
作者单位	Department of Microbiology and Immunology, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, United States
推荐引用方式 GB/T 7714	Teoh W.P.,Chen X.,Laczkovich I.,et al. Staphylococcus aureus adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement[J],2021,118(13).
APA	Teoh W.P.,Chen X.,Laczkovich I.,Alonzo F.,&III.(2021).Staphylococcus aureus adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Teoh W.P.,et al."Staphylococcus aureus adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).