气候变化领域集成服务门户(CCPortal): Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts

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DOI	10.1073/pnas.2104073118
	Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts
	Price S.L.; Vadyvaloo V.; De Marco J.K.; Brady A.; Gray P.A.; Kehl-Fie T.E.; Garneau-Tsodikova S.; Perry R.D.; Lawrenz M.B.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:44
英文摘要	Yersinia pestis causes human plague and colonizes both a mammalian host and a flea vector during its transmission cycle. A key barrier to bacterial infection is the host's ability to actively sequester key biometals (e.g., iron, zinc, and manganese) required for bacterial growth. This is referred to as nutritional immunity. Mechanisms to overcome nutritional immunity are essential virulence factors for bacterial pathogens. Y. pestis produces an iron-scavenging siderophore called yersiniabactin (Ybt) that is required to overcome iron-mediated nutritional immunity and cause lethal infection. Recently, Ybt has been shown to bind to zinc, and in the absence of the zinc transporter ZnuABC, Ybt improves Y. pestis growth in zinc-limited medium. These data suggest that, in addition to iron acquisition, Ybt may also contribute to overcoming zinc-mediated nutritional immunity. To test this hypothesis, we used a mouse model defective in iron-mediated nutritional immunity to demonstrate that Ybt contributes to virulence in an iron-independent manner. Furthermore, using a combination of bacterial mutants and mice defective in zinc-mediated nutritional immunity, we identified calprotectin as the primary barrier for Y. pestis to acquire zinc during infection and that Y. pestis uses Ybt to compete with calprotectin for zinc. Finally, we discovered that Y. pestis encounters zinc limitation within the flea midgut, and Ybt contributes to overcoming this limitation. Together, these results demonstrate that Ybt is a bona fide zinc acquisition mechanism used by Y. pestis to surmount zinc limitation during the infection of both the mammalian and insect hosts. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Insect vectors; Nutritional immunity; Siderophores; Yersinia pestis and plague; Zinc acquisition
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/238766
作者单位	Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, United States; Paul G. Allen School for Global Health, Washington State University, Pullman, WA 99164, United States; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40292, United States; Department of Microbiology and Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Champaign, IL 61820, United States; Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, KY 40536, United States; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky School of Medicine, Lexington, KY 40506, United States
推荐引用方式 GB/T 7714	Price S.L.,Vadyvaloo V.,De Marco J.K.,et al. Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts[J],2021,118(44).
APA	Price S.L..,Vadyvaloo V..,De Marco J.K..,Brady A..,Gray P.A..,...&Lawrenz M.B..(2021).Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts.Proceedings of the National Academy of Sciences of the United States of America,118(44).
MLA	Price S.L.,et al."Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts".Proceedings of the National Academy of Sciences of the United States of America 118.44(2021).