Fig 12. A genetic network in GBS for resisting Zn intoxication.

CopY represses copA but also activates sczA expression¹; which in turn controls czcD for Zn efflux²; CopY also activates riboflavin synthesis and/or transport³, arginine deamination and transport⁴, other targets⁵ and represses adcA⁶. Zn intoxication is inhibitory towards Zn acquisition⁷, de novo nucleotide⁸ and riboflavin synthesis⁹ pathways, cell wall synthesis genes¹⁰ and Stp1¹¹; Zn intoxication activates sczA¹² and arginine deaminase¹³. Stp1 represses activity of CovR¹⁴ and activates de novo purine synthesis¹⁵. CovR has activation roles for riboflavin¹⁶ and nucleotide synthesis genes¹⁷ and sczA¹⁸; Virulence and pathogenesis require contributions from CovR¹⁹ and CopY²⁰. Resistance to Zn stress requires functional czcD²¹, sczA²² covR²³, copY²⁴ and there are yet to be determined mechanisms of cell wall synthesis genes²⁵, nucleotide²⁶ and riboflavin synthesis²⁷ and arginine deamination²⁸ processes that contribute to Zn resistance in GBS. Dotted lines indicate contributions that remain to be characterized. Terms activation and repression refer to gene or protein regulatory activities, inhibitory and contribution refer to pathway or process level interactions. Interactions are based on gene expression data, phenotypes of isogenic mutants, cell and animal assays or prior published literature [20,21,28,35,92,93].