Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI) characterized
by bacterial biofilm formation and recalcitrance to immune-mediated clearance and antibiotics.
The molecular events behind PJI infection are yet to be unraveled. In this sense, identification of
polymorphisms in bacterial genomes may help to establish associations between sequence variants
and the ability of S. aureus to cause PJI. Here, we report an experimental nucleotide-level survey
specifically aimed at the intergenic regions (IGRs) of the icaADBCR locus, which is responsible for
the synthesis of the biofilm exopolysaccharide PIA/PNAG, in a collection of strains sampled from
PJI and wounds. IGRs of the icaADBCR locus were highly conserved and no PJI-specific SNPs were
found. Moreover, polymorphisms in these IGRs did not significantly affect transcription of the
icaADBC operon under in vitro laboratory conditions. In contrast, an SNP within the icaR coding
region, resulting in a V176E change in the transcriptional repressor IcaR, led to a significant increase
in icaADBC operon transcription and PIA/PNAG production and a reduction in S. aureus virulence
in a Galleria mellonella infection model. In conclusion, SNPs in icaADBCR IGRs of S. aureus isolates
from PJI are not associated with icaADBC expression, PIA/PNAG production and adaptation to PJI.
