Clumping Factor B Promotes Adherence of Staphylococcus aureus to Corneocytes in Atopic Dermatitis

Abstract

Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonization in AD patients. ClfB is a key adhesion molecule for the interaction of S. aureus with AD corneocytes and represents a target for intervention.

The role of filaggrin in atopic dermatitis and allergic disease

“…Filaggrin momomers are deamimated and degraded by proteases, releasing a pool of hygroscopic amino acids and derivatives of the NMF. Adapted from Fleury et al 122 exist in children of African ancestry and are associated with AD and a more persistent phenotype. 29 Sanger sequencing the entire FLG coding region for large cohorts is the gold standard for classifying patients.…”

“…SA binds via its clumping factor B, whose expression is up-regulated by decreased levels of NMF. 122,123 Commensal coagulase-negative staphylococci produce bactericidal peptides that inhibit SA biofilm formation. Commensal numbers are reduced in the early stages of AD.…”

Staphylococcal Biofilms in Atopic Dermatitis

“…Likewise, the S. aureus MSCRAMM clumping factor B (ClfB) that binds to fibrinogen and several other extracellular matrix proteins was shown to be important in biofilm formation under calcium-depleted conditions [72]. ClfB was recently implicated in facilitating attachment of S. aureus to the stratum corneum [73]. While the binding activity of ClfB varies among S. aureus strains assessed, these studies provide a molecular basis for how S. aureus may initiate colonization on AD skin.…”

Microbes: Fighting for space on a fragile interface

“…It has been found that fibronectin-binding proteins present on S. aureus, such as clumping factor B, can bind to fibronectin in AD subjects (which is not normally present in healthy skin)indicating fibronectin as a ligand candidate contributing to increased colonization. Further, facial keratinocytes, which are affected during the pathogenesis of AD, may help to reduce binding by clumping factor B in healthy skin by decreasing corneocyte levels of structural proteins loricrin and keratin 10 [17][18][19][20].…”