The role of zinc acquisition and zinc tolerance in group A streptococcal infection

Zinc plays an important role in host innate immune function. However, the innate immune system also utilizes zinc starvation ('nutritional immunity') to combat infections. Here, we investigate the role of zinc import and export in protection of(Group A; 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 (Δ) and export (Δ) deletion mutants in competition with wild-type in bothandvirulence 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

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies

Author correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

An amendment to this paper has been published and can be accessed via a link at the top of the paper