Characterization of a Propionibacterium acnes Surface Protein as a Fibrinogen-Binding Protein

Abstract

Propionibacterium acnes (P. acnes) is a major skin-associated bacterium that was long considered commensal, until several studies revealed it to be an opportunistic pathogen. We investigated the ability of P. acnes surface proteins to recognize ECM proteins and showed that a 58 kDa P. acnes surface protein was specifically recognized by human fibrinogen (hFg). The 58 kDa protein was further characterized by two-dimensional (2-D) electrophoresis and MALDI-ToF as a P. acnes host cell-surface attachment protein, PA25957, recognizing dermatan sulfate (DsA1). This protein sequence contains 432 amino acids with the presence of three structurally different domains: an N-terminal signal peptide, a C-terminal LPXTG motif, and a PT repeat region. DsA1 is mostly produced during stationary phase. It appears to be highly glycosylated, containing GalNAc residues. Purified DsA1 strongly recognizes the Aα and Bβ subunits of hFg, and specific enzymatic deglycosylation of hFg demonstrated the involvement of the protein backbone in the recognition process. The Bβ subunit of hFg was cloned in four peptide fractions (Fg1-Fg4). The N-terminal Fg1 peptide of hFg was recognized by DsA1, and priming DsA1 with Fg1 inhibited DsA1/hFg recognition. We describe here for the first time, the characterization of a P. acnes surface glycoprotein recognizing human fibrinogen.

Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue

“…This insertion contains four genes; two of them encode proteins with signal peptides, indicative of their export ( Figure 3 ). One protein (APS60_12543) contains PT repeats that are also found in a few other surface-exposed C. acnes proteins, including the dermatan sulfate-binding adhesin DsA1 that has recently been characterized as fibrinogen-binding protein ( Grange et al, 2017 ). The adjacent gene encodes a sortase of the SrtE family.…”

“…Two C. acnes factors, CAMP factors and dermatan-sulfate adhesins (DsA1 and DsA2), are often mentioned with regard to their possible involvement in the proinflammatory activity of C. acnes ( Lodes et al, 2006 ; Liu et al, 2011 ; McDowell et al, 2011 , 2013 ; Nakatsuji et al, 2011 ; Lheure et al, 2016 ; Grange et al, 2017 ). We could show here that type II strains produce high levels of CAMP factors 1 and 2; the proteins were found with a high coverage, indicative of their abundancy.…”

“…Dermatan-sulfate adhesins DsA1 and DsA2 of C. acnes have been partially characterized ( Lodes et al, 2006 ; McDowell et al, 2011 ; Grange et al, 2017 ). They were found to be abundant in the secreted as well as surface-exposed fraction of C. acnes ( Holland et al, 2010 ; Yu et al, 2016 ); moreover, they have been detected in human sebaceous follicles ( Bek-Thomsen et al, 2014 ).…”

“…They were found to be abundant in the secreted as well as surface-exposed fraction of C. acnes ( Holland et al, 2010 ; Yu et al, 2016 ); moreover, they have been detected in human sebaceous follicles ( Bek-Thomsen et al, 2014 ). A recent study has shown that DsA1 is highly glycosylated and recognizes human fibrinogen; thus, it is considered to be a MSCRAMM (microbial surface component recognizing adhesive matrix molecules) ( Grange et al, 2017 ). The DsA1 protein sequence contains a repetitive motif of proline and threonine (PT repeats); the authors suggested that theses PT repeats could be responsible for fibrinogen-binding.…”

Platelet activation and aggregation by the opportunistic pathogen Cutibacterium (Propionibacterium) acnes

“…C . acnes was recently shown to have specific fibrinogen-binding proteins [ 63 ], and has earlier been shown to secrete proteins capable of interacting with TLR2-receptors [ 64 ], possibly partaking in the aggregation of platelets. It is however currently unknown as to what percentage of clinical strains carry this gene, as well as if it is involved in platelet aggregation.…”