SpxA1 and SpxA2 Function as a Stoichiometry-Dependent Regulatory Rheostat Governing Virulence Gene Expression in Group A Streptococcus — CovR ChIP-exo dataset

SpxA2 is directly regulated by the LiaFSR three-component system in response to antimicrobial peptide stress. To define how SpxA2 influences CovR DNA occupancy genome-wide, we performed chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) targeting CovR in wild-type MGAS10870 (emm3), an isogenic spxA2 deletion mutant (deltaSpxA2), and a LiaSQ146A constitutively active LiaS mutant used as a SpxA2 overexpression surrogate (SpxA2-OE).

Differential binding analysis identified 439 sites with significantly altered CovR occupancy between wild-type and deltaSpxA2 (FDR < 0.05), with class-specific enrichment of CovR dimer and monomer binding motifs consistent with the two-class CovR binding model (Horstmann et al. 2023). These data contribute to a multi-omic analysis including RNA-seq, DIA proteomics, and NanoString nCounter that defines the regulatory roles of SpxA1 and SpxA2 in GAS pathogenesis.