A Critical Role of Zinc Importer AdcABC in Group A Streptococcus-Host Interactions During Infection and Its Implications for Vaccine Development

Nishanth Makthal, Kimberly Nguyen, Hackwon Do, Maire Gavagan, Pete Chandrangsu, John D. Helmann, Randall J. Olsen, Muthiah Kumaraswami

Research output: Contribution to journalArticle

18 Scopus citations

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 languageEnglish (US)
Pages (from-to)131-141
Number of pages11
JournalEBioMedicine
Volume21
DOIs
StatePublished - 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)

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