The Sortase A Substrates FnbpA, FnbpB, ClfA and ClfB Antagonize Colony Spreading of Staphylococcus aureus

Tsompanidou, Eleni; Denham, Emma L.; Sibbald, Mark J. J. B.; Yang, Xiao-Ning; Seinen, Jolien; Friedrich, Alexander; Buist, Girbe; Dijl, Jan Maarten van

doi:10.1371/journal.pone.0044646

Cited by 44 publications

(38 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ClfA, FnBPA/B and SpA) are covalently bound to the cell wall by a transpeptidase, SrtA. Absence of SrtA leads to the defective anchoring of about 20 staphylococcal surface proteins . Our findings indicate that the srtA gene and the subsequent correct anchoring of staphylococcal surface proteins are vital for S. aureus binding to the vascular endothelium via VWF.…”

Section: Discussionmentioning

confidence: 80%

Clumping factor A, von Willebrand factor‐binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall

Claes

Liesenborghs

Peetermans

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Objective: When establishing endovascular infections, Staphylococcus aureus (S. aureus) overcomes shear forces of flowing blood by binding to von Willebrand factor (VWF). Staphylococcal VWF-binding protein (vWbp) interacts with VWF, but it is unknown how this secreted protein binds to the bacterial cell wall. We hypothesized that vWbp interacts with a staphylococcal surface protein, mediating the adhesion of S. aureus to VWF and vascular endothelium under shear stress. Methods: We studied the binding of S. aureus to vWbp, VWF and endothelial cells in a micro-parallel flow chamber using various mutants deficient in Sortase A (SrtA) and SrtA-dependent surface proteins, and Lactococcus lactis expressing single staphylococcal surface proteins. In vivo adhesion of bacteria was evaluated in the murine mesenteric circulation using real-time intravital vascular microscopy. Results: vWbp bridges the bacterial cell wall and VWF, allowing shear-resistant binding of S. aureus to inflamed or damaged endothelium. Absence of SrtA and Clumping factor A (ClfA) reduced adhesion of S. aureus to vWbp, VWF and activated endothelial cells. ADAMTS-13 and an anti-VWF A1 domain antibody, when combined, reduced S. aureus adhesion to activated endothelial cells by 90%. Selective overexpression of ClfA in the membrane of Lactococcus lactis enabled these bacteria to bind to VWF and activated endothelial cells but only in the presence of vWbp. Absence of ClfA abolished bacterial adhesion to the activated murine vessel wall. Conclusions: vWbp interacts with VWF and with the SrtA-dependent staphylococcal surface protein ClfA. The complex formed by VWF, secreted vWbp and bacterial ClfA anchors S. aureus to vascular endothelium under shear stress.

show abstract

Section: Discussionmentioning

confidence: 80%

Clumping factor A, von Willebrand factor‐binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall

Claes

Liesenborghs

Peetermans

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…There are around 20 staphylococcal proteins that carry a C-terminal LPXTG motif, including protein A (Spa), two fibronectin binding proteins (FnbpA and FnbpB), two clumping factors (ClfA and ClfB), a collagen-binding protein (Cna) and three serine-aspartate repeat proteins (SdrC, SdrD, and SdrE) [12]. For some of these proteins, a direct role in biofilm formation has been reported [13] (Table 1).…”

Section: Sortase a Is An Ideal Antivirulence Targetmentioning

confidence: 99%

Sortase A: An ideal target for anti-virulence drug development

Cascioferro¹,

Totsika²,

Schillaci³

2014

Microbial Pathogenesis

160

142

View full text Add to dashboard Cite

“…However, Agr is also needed for biofilm formation, which gives it a decisive role in the choice between motile and sessile lifestyles of S. aureus. Furthermore, it was shown that covalently cell wall-anchored proteins, like FnbpA, FnbpB, ClfA, and ClfB, can set a limit to the colony-spreading ability of S. aureus cells (28). To date, very little was known about the roles of individual PSM peptides in colony spreading and whether these are the main factors promoting spreading.…”

Section: S Taphylococcus Aureus Is An Opportunistic Human Pathogen Thatmentioning

confidence: 99%

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Tsompanidou

Denham

Becher

et al. 2013

Appl Environ Microbiol

Self Cite

View full text Add to dashboard Cite

The human pathogen Staphylococcus aureus is renowned for the rapid colonization of contaminated wounds, medical implants, and food products. Nevertheless, little is known about the mechanisms that allow S. aureus to colonize the respective wet surfaces. The present studies were therefore aimed at identifying factors used by S. aureus cells to spread over wet surfaces, starting either from planktonic or biofilm-associated states. Through proteomics analyses we pinpoint phenol-soluble modulins (PSMs) as prime facilitators of the spreading process. To dissect the roles of the eight PSMs produced by S. aureus, these peptides were chemically synthesized and tested in spreading assays with different psm mutant strains. The results show that PSM␣3 and PSM␥ are the strongest facilitators of spreading both for planktonic cells and cells in catheter-associated biofilms. Compared to the six other PSMs of S. aureus, PSM␣3 and PSM␥ combine strong surfactant activities with a relatively low overall hydropathicity. Importantly, we show that PSM-mediated motility of S. aureus facilitates the rapid colonization of wet surfaces next to catheters and the colonization of fresh meat. S taphylococcus aureus is an opportunistic human pathogen thatcan cause a wide range of acute and chronic diseases, which range from superficial skin infections to life-threatening endocarditis and sepsis (1, 2). The ability of this Gram-positive bacterium to cause these infections depends on the production of secreted and cell wall-associated virulence factors. Of increasing concern is the ability of S. aureus to acquire resistance against antibiotics, as underscored by the global spread of methicillin-resistant S. aureus (MRSA) lineages.Intriguingly, recent proteomics studies have revealed an enormous diversity in the production of virulence factors by different isolates of S. aureus, and only a few of these seem to be invariantly produced (3-5). Among the most commonly identified staphylococcal virulence factors, especially in the community-associated (CA)-MRSA lineages, are the so-called phenol-soluble modulins (PSMs) (6). These PSMs are short, amphipathic, ␣-helical peptides that have leukocidal activity and biosurfactant properties (7-9). The growth media of S. aureus cultures contain both N-terminally formylated and deformylated PSMs, suggesting that these virulence factors are substrates for the bacterial N-formylmethionine deformylase (9, 10).To date, eight PSMs have been identified in S. aureus. These include the four PSM␣1 to PSM␣4 peptides (22 residues each), the PSM␤1 and PSM␤2 peptides (44 residues each), PSM␥ (25 residues) and the recently reported PSM-mec (22 residues). The PSM␣ peptides are encoded by the psm␣ operon, the PSM␤ peptides by the psm␤ operon, and PSM␥ by the hld gene. Notably, the hld gene is embedded within the regulatory RNAIII molecule that is encoded by the agr locus. The gene for PSM-mec was identified in MRSA strains carrying the staphylococcal cassette chromosome mec (SCCmec) types II or III. The expression of all ps...

show abstract

The Sortase A Substrates FnbpA, FnbpB, ClfA and ClfB Antagonize Colony Spreading of Staphylococcus aureus

Cited by 44 publications

References 59 publications

Clumping factor A, von Willebrand factor‐binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall

Clumping factor A, von Willebrand factor‐binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall

Sortase A: An ideal target for anti-virulence drug development

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Contact Info

Product

Resources

About