Abstract
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.
Original language | English (US) |
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Pages (from-to) | 131-141 |
Number of pages | 11 |
Journal | EBioMedicine |
Volume | 21 |
DOIs | |
State | Published - Jul 2017 |
Keywords
- GAS vaccine
- Gene regulation
- Group A streptococcus
- Host-pathogen interactions
- Nutritional immunity
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)