[HTML][HTML] A critical role of zinc importer AdcABC in group A Streptococcus-host interactions during infection and its implications for vaccine development

N Makthal, K Nguyen, H Do, M Gavagan… - …, 2017 - thelancet.com
N Makthal, K Nguyen, H Do, M Gavagan, P Chandrangsu, JD Helmann, RJ Olsen
EBioMedicine, 2017thelancet.com
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 …
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.
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