期刊
EBIOMEDICINE
卷 21, 期 -, 页码 131-141出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.05.030
关键词
Group A streptococcus; Host-pathogen interactions; Nutritional immunity; Gene regulation; GAS vaccine
资金
- National Institute of Health [1R01AI109096-01A1, GM059323]
Bacterial pathogens must overcome host immune mechanisms to acquire micronutrients for successful replication and infection. Streptococcus pyogenes, also known as group A streptococcus (GAS), is a human pathogen that causes a variety of clinical manifestations, and disease prevention is hampered by lack of a human GAS vaccine. Herein, we report that the mammalian host recruits calprotectin (CP) to GAS infection sites and retards bacterial growth by zinc limitation. However, a GAS-encoded zinc importer and a nuanced zinc sensor aid bacterial defense against CP-mediated growth inhibition and contribute to GAS virulence. Immunization of mice with the extracellular component of the zinc importer confers protection against systemic GAS challenge. Together, we identified a key early stage host-GAS interaction and translated that knowledge into a novel vaccine strategy against GAS infection. Furthermore, we provided evidence that a similar struggle for zinc may occur during other streptococcal infections, which raises the possibility of a broad-spectrum prophylactic strategy against multiple streptococcal pathogens. (C) 2017 The Authors. Published by Elsevier B.V.
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