Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Pietrocola, Giampiero; Nobile, Giulia; Alfeo, Mariangela J.; Foster, Timothy J.; Geoghegan, Joan A.; Filippis, Vincenzo De; Speziale, Pietro

doi:10.1074/jbc.ra118.005707

Cited by 37 publications

(34 citation statements)

References 57 publications

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“…We have discovered that FnBPB and ClfB are CDSN binding proteins. In addition to CDSN, the N2N3 subdomains of FnBPB bind to fibrinogen, elastin, plasminogen, and histone H3 ( 34 – 36 ), while ClfB N2N3 binds to fibrinogen, loricrin, and K10 ( 19 ). MSCRAMMs generally bind to ligands using the “dock, lock, and latch” mechanism ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis

Towell

Feuillie

Vitry

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Staphylococcus aureus colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of S. aureus to corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show that S. aureus interacts with the host protein corneodesmosin. Corneodesmosin is aberrantly displayed on the tips of villus-like projections that occur on the surface of AD corneocytes as a result of low levels of skin humectants known as natural moisturizing factor (NMF). An S. aureus mutant deficient in fibronectin binding protein B (FnBPB) and clumping factor B (ClfB) did not bind to corneodesmosin in vitro. Using surface plasmon resonance, we found that FnBPB and ClfB proteins bound with similar affinities. The S. aureus binding site was localized to the N-terminal glycine–serine-rich region of corneodesmosin. Atomic force microscopy showed that the N-terminal region was present on corneocytes containing low levels of NMF and that blocking it with an antibody inhibited binding of individual S. aureus cells to corneocytes. Finally, we found that S. aureus mutants deficient in FnBPB or ClfB have a reduced ability to adhere to low-NMF corneocytes from patients. In summary, we show that FnBPB and ClfB interact with the accessible N-terminal region of corneodesmosin on AD corneocytes, allowing S. aureus to take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding of S. aureus to AD corneocytes.

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Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis

Towell

Feuillie

Vitry

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…This protein is involved in the primary attachment phase to fibronectin, elastin, and fibrinogen, as well as in the accumulation process in biofilm formation ( 13 , 52 ). It has also been demonstrated that FnBPB favors cell invasion and protects against the antimicrobial activity of histones released during the neutrophils extracellular traps (NETs) ( 23 , 53 ). Since we did not evaluate the presence of this marker in the other two native strains tested, we cannot discuss its influence in the invasion capacity.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Characterization and Whole Genome Analysis of a Strong Biofilm-Forming Staphylococcus aureus Strain Associated With Subclinical Bovine Mastitis in Colombia

et al. 2020

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Staphylococcus aureus represent a serious threat to public health due to food safety, antibiotic resistance, and the potential zoonotic transmission of strains between dairy cattle and humans. Biofilm formation by S. aureus results in chronicity of the infections which confers protection against the immune response and antibiotics. Likewise, biofilm allows the exchange of mobile genetic material among different strains through microbial interactions inside the matrix. In Colombia, where S. aureus continues to be one of the main pathogens isolated from bovine intramammary infections and where milking by hand is highly frequent, there are knowledge gaps on the zoonotic potential of the strains. Therefore, the aim of this work was to characterize genotypically and phenotypically the S. aureus Sa1FB strain with strong biofilm production and to perform genomic and phenotypic comparisons with other relevant S. aureus strains (native and references strains). These results show a highly productive strain of biofilm and a low ability of cell invasion compared to the other two native strains. In addition, high genomic similarity between S. aureus Sa1FB and the reference strains was observed, despite of the differences reported at the clinical level. However, Sa1FB exhibited special features in terms of mobile genetic elements, highlighting its ability to accept foreign genetic material. Indeed, this could increase mutation, pathogenesis, and adaptability to new hosts, representing a risk for people in contact with the milk obtained from animals infected with these strains. These results present the relevance of surveillance for early detection of emergent clones with zoonotic potential, which reduces the risk of occupational exposure and their spread in the community.

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“…Histones have potent antimicrobial activity due to properties similar to cationic antimicrobial peptides. Histones H2A, H3 and H4 have been shown to have anti-staphylococcal activity ( Morita et al, 2013 ; Pietrocola et al, 2019 ).…”

Section: Ligands Of Fnbpa/fnbpbmentioning

confidence: 99%

“…Alternatively, FnBPB can bind to Plg which, when activated to plasmin, can cleave the sequestered histone. Also FnBPB expression was shown to be responsible for protecting S. aureus from the bactericidal effect of the total histones released by neutrophils in the form of NETs ( Pietrocola et al, 2019 ). Finally, the A domain of FnBPB can also bind to Fn by a mechanism that does not involve DLL ( Burke et al, 2010 ).…”

Section: Mechanisms Of Fnbps Interaction With Ligandsmentioning

confidence: 99%

“…FnBPs were found to be involved in invasion of a variety of several non-phagocytic cell lines ( Sinha et al, 1999 ; Liang et al, 2016 ; Prystopiuk et al, 2018 ). Furthermore, FnBPs were shown to bind to elastin ( Roche et al, 2004 ), plasminogen (Plg) ( Pietrocola et al, 2016 ) and histones ( Pietrocola et al, 2019 ) and to have an important role in the formation of biofilm ( O’Neill et al, 2008 ; Geoghegan et al, 2013 ; Speziale et al, 2014 ; Herman-Bausier et al, 2015 ). This multifactorial capacity to bind several ligands is closely related to the pathogenicity of the bacterium.…”

Section: Introductionmentioning

confidence: 99%

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The Multivalent Role of Fibronectin-Binding Proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in Host Infections

Speziale

Pietrocola

2020

Front. Microbiol.

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Staphylococcus aureus, one of the most important human pathogens, is the causative agent of several infectious diseases including sepsis, pneumonia, osteomyelitis, endocarditis and soft tissue infections. This pathogenicity is due to a multitude of virulence factors including several cell wall-anchored proteins (CWA). CWA proteins have modular structures with distinct domains binding different ligands. The majority of S. aureus strains express two CWA fibronectin (Fn)-binding adhesins FnBPA and FnBPB (Fn-binding proteins A and B), which are encoded by closely related genes. The N-terminus of FnBPA and FnBPB comprises an A domain which binds ligands such as fibrinogen, elastin and plasminogen. The A domain of FnBPB also interacts with histones and this binding results in the neutralization of the antimicrobial activity of these molecules. The C-terminal moiety of these adhesins comprises a long, intrinsically disordered domain composed of 11/10 fibronectin-binding repeats. These repetitive motifs of FnBPs promote invasion of cells that are not usually phagocytic via a mechanism by which they interact with integrin α 5 β 1 through a Fn mediated-bridge. The FnBPA and FnBPB A domains engage in homophilic cell-cell interactions and promote biofilm formation and enhance platelet aggregation. In this review we update the current understanding of the structure and functional properties of FnBPs and emphasize the role they may have in the staphylococcal infections.

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Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones

Cited by 37 publications

References 57 publications

Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis

Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis

Phenotypic Characterization and Whole Genome Analysis of a Strong Biofilm-Forming Staphylococcus aureus Strain Associated With Subclinical Bovine Mastitis in Colombia

The Multivalent Role of Fibronectin-Binding Proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in Host Infections

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