Experimental Polymorphism Survey in Intergenic Regions of the Locus in Isolates from Periprosthetic Joint Infections.

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 to cause PJI. Here, we report an experimental nucleotide-level survey specifically aimed at the intergenic regions (IGRs) of the 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 locus were highly conserved and no PJI-specific SNPs were found. Moreover, polymorphisms in these IGRs did not significantly affect transcription of the operon under in vitro laboratory conditions. In contrast, an SNP within the coding region, resulting in a V176E change in the transcriptional repressor IcaR, led to a significant increase in operon transcription and PIA/PNAG production and a reduction in virulence in a infection model. In conclusion, SNPs in IGRs of isolates from PJI are not associated with expression, PIA/PNAG production and adaptation to PJI.