Group B streptococcus (GBS) is the leading cause of mortality due to bacterial infection in infants and is vertically transmitted from mother to baby during birth. Life-threatening neonatal complications arise from meningitis, sepsis and pneumonia. GBS also causes disease in immunocompromised, elderly and otherwise healthy adults. GBS exists as a commensal in the gastrointestinal and urogenital tracts of humans and infects as an opportunistic pathogen. Survival in body niches depends on numerous virulence factors(1) and metabolic pathways(2), including the ability to resist stress due to metal ion intoxication in the host.
Copper (Cu) and Zinc (Zn) efflux systems in GBS confer survival advantages during metal intoxication(3, 4). Here we present a molecular dissection of genes required to survive excess Cu or Zn conditions using RNASeq and TraDIS approaches. We identify new networks of genes linked to Cu and Zn stress, encompassing biological processes not previously associated with metal stress in bacteria; including amino acid transporters, putative enzymes for cell-wall synthesis, arginine metabolism and nucleotide synthesis, and effectors in global regulation of bacterial virulence. Identification of metal ion resistance systems required for disseminated infection or colonisation of the genital tract in mice suggests these mechanisms of resistance to Zn and Cu intoxication might represent new avenues for research into GBS control.