Transcriptomic analysis of Streptococcus agalactiae periprosthetic joint infection

Abstract

Although Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection is not uncommon. Here, RNA‐seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. A total of 227 genes with outlier expression were found (164 upregulated and 63 downregulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding β‐hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a resource for identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections.

Genomic characterization of beta‐haemolytic streptococci isolated from prosthetic joint infections

“…These results may therefore indicate that biofilm formation in S. agalactiae is often encoded by genes other than PI‐2A . This aligns with the findings of Cho et al (15), which suggested that PJI biofilm could also be produced by isolates not carrying these pilus genes.…”

“…These results may therefore indicate that biofilm formation in S. agalactiae is often encoded by genes other than PI-2A. This aligns with the findings of Cho et al (15), which suggested that PJI biofilm could also be produced by isolates not carrying these pilus genes. Among the S. dysgalactiae isolates, speS was found in GCS to a larger extent than in GGS (100% vs 46.7%), possibly indicating a more virulent GCS lineage relative to GGS.…”

“…There is limited evidence regarding whether certain streptococcal CCs dominate, whether antimicrobial resistance (AMR) is widespread and whether certain virulence genes characterize the isolates causing streptococcal PJIs. However, Cho et al (15) examined the transcriptome of six S. agalactiae isolates from PJI and reported that genes related to inorganic ion transport and metabolism were upregulated compared to a reference strain. They hypothesized that biofilm formation in streptococcal PJI is dependent on the expression of non-pilus island-encoded adhesins.…”

“…Streptococcal species are known to produce biofilm and exhibit adhesins and exotoxins, but genomic characterization of streptococcal PJIs is a relatively unexplored field. To the best of our knowledge, only two previous studies have investigated the genomic aspects of PJI-causing streptococci (14,15), though the genomic traits of staphylococcal species from PJI have been investigated to a larger extent. Wildeman et al (16) concluded that S. aureus isolates from PJIs do not differ from commensal nasal isolates of S. aureus.…”

Streptococcal peptides and their roles in host-microbe interactions

“…The most well-studied of these genes regulated by the RovS/SHP1520 system are those that are found in the cyl operon that is responsible for the production of the GBS β-hemolysin/cytolysin (β-H/C, CylE), which has several roles in the context of infection ( Pritzlaff et al., 2001 ; Rajagopal, 2009 ). This virulence factor is associated with increased inflammation during GBS-mediated arthritis, and is significantly upregulated in GBS prosthetic joint infections ( Puliti et al., 2000 ; Cho et al., 2021 ). The increase in disease severity caused by hyperhemolytic mutants in an arthritis model correlated with an increase in both local and systemic levels of the pro-inflammatory cytokine IL-6 ( Puliti et al., 2000 ).…”