The N-terminal domain of the thermo-regulated surface protein PrpA of Enterococcus faecium binds to fibrinogen, fibronectin and platelets

Abstract

Enterococcus faecium is a commensal of the mammalian gastrointestinal tract, but is also found in non-enteric environments where it can grow between 10 °C and 45 °C. E. faecium has recently emerged as a multi-drug resistant nosocomial pathogen. We hypothesized that genes involved in the colonization and infection of mammals exhibit temperature-regulated expression control and we therefore performed a transcriptome analysis of the clinical isolate E. faecium E1162, during mid-exponential growth at 25 °C and 37 °C. One of the genes that exhibited differential expression between 25 °C and 37 °C, was predicted to encode a peptidoglycan-anchored surface protein. The N-terminal domain of this protein is unique to E. faecium and closely related enterococci, while the C-terminal domain is homologous to the Streptococcus agalactiae surface protein BibA. This region of the protein contains proline-rich repeats, leading us to name the protein PrpA for proline-rich protein A. We found that PrpA is a surface-exposed protein which is most abundant during exponential growth at 37 °C in E. faecium E1162. The heterologously expressed and purified N-terminal domain of PrpA was able to bind to the extracellular matrix proteins fibrinogen and fibronectin. In addition, the N-terminal domain of PrpA interacted with both non-activated and activated platelets.

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections

“…However, there were exceptions, including two strains with a low level of EbpA expression but a high level of fibrinogen binding. That these atypical strains colonized bladder and catheter in the CAUTI model but were susceptible to EbpA NTD -based immunotherapy suggests that Ebp pili play a critical role in CAUTI pathogenesis that cannot be compensated for by other Fg-binding activities that can be expressed by enterococci, including Fss proteins and PrpA (25, 33). It is possible that heterogeneity in regulation of Ebp means that pilus expression in vitro may not reflect levels in vivo .…”

Emerging Risks in Food: Probiotic Enterococci Pose a Threat to Public Health through the Food Chain

“…Cell-surface-associated virulence genes could contribute to biofilm formation and adhesion to host tissues. In addition, acm [26], efaA [27], ebp [28], and gls24 [29] are involved in the pathogenesis of endocarditis; scm has a high prevalence in clinically related E. faecium [30]; sgrA and ecbA are the marker for clinically associated E. faecium [31]; bopD contributes to prolonged mouse bacteremia [32]; prpA is proposed to contribute to colonization and infection, and its N-terminus is able to bind to fibrinogen, fibronectin and platelets [33]; cad contributes to facilitating conjugation, chemotactic for human neutrophils [34]. Therefore, the wide spectrum of VGs in these enterococcal isolates allows them to cause infection and disease.…”

Virulence Determinants of Enterococcus faecium

“…Another protein upregulated at 37°C, identified through transcriptomic analysis, is the proline-rich protein PrpA, which binds to extracellular matrix proteins such as fibrinogen and fibronectin, mediating adherence to platelets. However, the precise role of PrpA in colonization or infection remains elusive [13]. Another surface adhesin, the serine-glutamate repeat-containing protein A (SgrA), binds to nidogen 1 and nidogen 2, two components of the basal lamina, as well as fibrinogen.…”

“…As for E. faecalis, pathogenicity of E. faecium stems from a diverse array of virulence factors, enabling adhesion to host tissues, evasion of the immune system, and establishment of persistent infections [7]. Key among these factors are cell surface components and secreted proteins, which play pivotal roles in mediating interactions between the pathogen and its host and facilitate initial adhesion and biofilm formation, enhancing the pathogen's ability to persist and cause chronic infections [8][9][10][11][12][13][14]. E. faecium also produces bacteriocins which confer a competitive advantage by inhibiting the growth of competing bacteria as well as temperature-regulated gene expression that enhances adherence and biofilm formation, thereby augmenting bacterial virulence [15,16].…”