Metals like copper (Cu) and zinc (Zn) are essential trace elements that play a crucial role in bacterial cell physiology. However, elevated concentrations of these metals can also be toxic to bacteria. Various distinct genetic mechanisms for regulating the efflux of copper and zinc have been identified in several bacterial pathogens, including streptococci. These include the canonical copA-copY and czcD-sczA efflux systems in Group B Streptococcus (GBS).
RNA-seq analyses, coupled with Transposon Directed Insertion Site Sequencing (TraDIS) experiments we previously performed uncovered a suite of genes that are differentially expressed and/or required for survival under either Cu of Zn stress. These genes encode for diverse processes related to import/export, metabolism, cell structure and signalling, none of which have been linked to metal ion resistance in other bacteria. Here, we explore the role of these genes in mediating resistance to other host-mediated immune responses/stresses such as reactive oxygen species (ROS; H2O2) and reactive nitrogen species (RNS; S-nitoso-n-acetylpenicillamine (SNAP)). Selected genes from this pool were also investigated in a well-defined murine infection model of the human female reproductive tract.