Oral Presentation BACPATH 2019

The role of zinc acquisition and zinc tolerance in Group A Streptococcal infection (#21)

Cheryl-Lynn Y. Ong 1 , Olga Berking 1 , Mark J Walker 1 , Alastair G McEwan 1
  1. School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia

Zinc is an important nutrient in biology. Zinc deficiency is associated with increased susceptibility to bacterial infections. Since the innate immune system can utilise both zinc starvation and toxicity strategies to combat infections, therefore, bacterial pathogens need strict control of zinc homeostasis. Here, we investigate the role of zinc import and export in protection of Streptococcus pyogenes (Group A Streptococcus; GAS), a Gram-positive bacterial pathogen responsible for a wide spectrum of human diseases, against challenge from host innate immune defence. In order to determine the role of GAS zinc import and export during infection, we utilized the zinc import (ΔadcA/AII) and export (ΔczcD) deletion mutants in competition with wild-type in both in vitro and in vivo virulence models. We demonstrate that nutritional immunity is deployed extracellularly while zinc toxicity is utilized upon phagocytosis of GAS by neutrophils. We also show that lysosomes and azurophilic granules in neutrophils contain zinc stores for use against intracellular pathogens. We identified that the stage and site of infection differ in the use of zinc as a control strategy.