Fig. 4: Mutations found in the accessory gene regulatory (Agr) system of colonizing strains.

a Protein-altering mutations in the protein domains of the sensor kinase AgrC and the response regulator AgrA. The N-terminal sensor domain of AgrC comprises six transmembrane domains (coloured in blue) and is connected to a conserved C-terminal histidine kinase (HK) domain (coloured in orange). The HK domain is made up of two subdomains: the dimerization and histidine phosphotransfer (DHp) subdomain and the catalytic and ATP-binding (CA) subdomain¹¹⁰. AgrA is comprised of a response regulatory domain (coloured in blue) and a DNA binding domain (coloured in orange). Isolates carrying mutations in bold were selected for haemolytic assays from available collections²³ to represent different types of mutations (i.e. missense, frameshift, stop gained and inframe indel) at each protein domain. b Haemolytic activities of S. aureus isolates on sheep blood agar (SBA) plates used to test the activity of the Agr system. For each mutation, two isolates from the same host were tested, one carrying a selected Agr mutation (mutant) and a second isolate being wild type for the Agr system. A positive result is indicated by a widening of haemolysis seen in the region of RN4220. c Intergenic region containing agr promoters. The black horizonal lines represent the extent of transcript starting at the promoter 3 transcriptional start site (P3 TST), which encodes for RNAIII, and the transcript starting at promoter 2, which contains the whole agrBDCA coding region. Light blue boxes represent -10 and -35 boxes, whereas orange boxes the AgrA binding sites (“AgrA tandem repeats”). The only intergenic mutation carried by an available isolate (C-49T) yielded a negative haemolytic assay, as well as the isolate from the same host lacking this mutation, the latter attributable to a frameshift mutation in AgrC. Mutations identified in a collection of 3,060 S. aureus isolate genomes from 791 individuals (see Supplementary Table 1). See Supplementary Data 5 for all mutations identified between colonising isolates of the same host. Source data are provided as a Source Data file.