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

Liliana Morales-Laverde,Iñigo Lasa,Cristina Solano,Maite Echeverz,Margarita Trobos

doi:10.3390/microorganisms10030600

Liliana Morales-Laverde, Iñigo Lasa + Show 3 more

Open Access

https://doi.org/10.3390/microorganisms10030600

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Abstract

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.

Highlights

Accepted: 4 March 2022Despite the efforts at improving infection control measures to reduce the risk of bacterial colonization of arthroplasty implants, the incidence of periprosthetic joint infections (PJI) remains high [1,2]
In S. aureus, intergenic SNPs have been found to be significantly associated with toxicity in methicillin-resistant strains (MRSA) [29] and highly divergent intergenic regions (IGRs) have been related to differences in gene expression [30]
No relevant differences in GFP levels were observed. These results demonstrated that the SNPs present in IGRs of the icaADBCR locus found in PJI

Summary

Introduction

Accepted: 4 March 2022Despite the efforts at improving infection control measures to reduce the risk of bacterial colonization of arthroplasty implants, the incidence of periprosthetic joint infections (PJI) remains high [1,2]. The attachment of S. aureus to the surface of the medical device can occur at the time of surgery or after implantation, once the surface is covered with plasma proteins. In the former case, adhesion of the bacteria to the naked surface is dependent on the physico-chemical characteristics of the device and the bacterial surface components [5]. Attachment to the implanted device mainly occurs through specific interactions between bacterial adhesins and plasma proteins [6,7]. S. aureus forms a biofilm due to the production of an extracellular matrix mainly composed of exopolysaccharides, proteins, and extracellular DNA [8,9]. The infection is difficult to treat because bacteria inside the biofilm grow protected from the attack of the immune system and antimicrobial agents [10,11]

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