BackgroundColonization of the skin by Staphylococcus aureus in individuals with atopic dermatitis exacerbates inflammation. Atopic dermatitis is associated with loss-of-function mutations in the filaggrin (FLG) gene, accompanied by reduced levels of filaggrin breakdown products on the skin.ObjectiveTo assess the affect of growth in the presence of the filaggrin breakdown products urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA) on fitness of and protein expression by S aureus.MethodsS aureus was grown for 24 hours in the presence of UCA and PCA, and the density of the cultures was monitored by recording OD600 values. Cell wall extracts and secreted proteins of S aureus were isolated and analyzed by SDS-PAGE. Cell wall–associated proteins known to be involved in colonization and immune evasion including clumping factor B, fibronectin binding proteins, protein A, iron-regulated surface determinant A, and the serine-aspartate repeat proteins were examined by Western immunoblotting.ResultsAcidification of growth media caused by the presence of UCA and PCA resulted in reduced growth rates and reduced final cell density of S aureus. At the lower pH, reduced expression of secreted and cell wall–associated proteins, including proteins involved in colonization (clumping factor B, fibronectin binding protein A) and immune evasion (protein A), was observed. Decreased expression of iron-regulated surface determinant A due to growth with filaggrin breakdown products appeared to be independent of the decreased pH.ConclusionS aureus grown under mildly acidic conditions such as those observed on healthy skin expresses reduced levels of proteins that are known to be involved in immune evasion.
BackgroundThe natural habitat of Staphylococcus aureus is the moist squamous epithelium in the anterior nares. About 20% of the human population carry S. aureus permanently in their noses and another 60% of individuals are intermittent carriers. The ability of S. aureus to colonize the nasal epithelium is in part due to expression of surface proteins clumping factor B (ClfB) and the iron-regulated surface determinant A (IsdA), which promote adhesion to desquamated epithelial cells present in the anterior part of the nasal vestibule. S. aureus strain Newman defective in IsdA and ClfB exhibited reduced but not completely defective adherence to squamous cells in indicating that other cell surface components might also contribute.ResultsSurface proteins IsdA, ClfB, and the serine-aspartic acid repeat proteins SdrC, SdrD and SdrE were investigated to determine their contribution to the adherence of S. aureus to desquamated nasal epithelial cells. This was achieved by expression of ClfB, IsdA, SdrC, SdrD and SdrE on the surface of the surrogate Gram-positive host Lactococcus lactis and by isolating mutants of S. aureus Newman defective in one or more factor. The level of adherence of strains to squamous cells isolated from the nares of volunteers was measured. Results consistently showed that ClfB, IsdA, SdrC and SdrD each contributed to the ability of S. aureus to adhere to squamous cells. A mutant lacking all four proteins was completely defective in adherence.ConclusionThe ability of S. aureus Newman to adhere to desquamated nasal epithelial cells is multifactorial and involves SdrD and SdrC as well as ClfB and IsdA.
Background Staphylococcus aureus permanently colonizes the vestibulum nasi of one-fifth of the human population, which is a risk factor for autoinfection. The precise mechanisms whereby S. aureus colonizes the nose are still unknown. The staphylococcal cell-wall protein clumping factor B (ClfB) promotes adhesion to squamous epithelial cells in vitro and might be a physiologically relevant colonization factor.Methods and FindingsWe define the role of the staphylococcal cytokeratin-binding protein ClfB in the colonization process by artificial inoculation of human volunteers with a wild-type strain and its single locus ClfB knock-out mutant. The wild-type strain adhered to immobilized recombinant human cytokeratin 10 (CK10) in a dose-dependent manner, whereas the ClfB− mutant did not. The wild-type strain, when grown to the stationary phase in a poor growth medium, adhered better to CK10, than when the same strain was grown in a nutrient-rich environment. Nasal cultures show that the mutant strain is eliminated from the nares significantly faster than the wild-type strain, with a median of 3 ± 1 d versus 7 ± 4 d (p = 0.006). Furthermore, the wild-type strain was still present in the nares of 3/16 volunteers at the end of follow-up, and the mutant strain was not.ConclusionsThe human colonization model, in combination with in vitro data, shows that the ClfB protein is a major determinant of nasal-persistent S. aureus carriage and is a candidate target molecule for decolonization strategies.
Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients is poorly understood. We describe here for the first time that the major virulence factor of S. aureus, protein A (SpA) binds directly to osteoblasts. This interaction prevents proliferation, induces apoptosis and inhibits mineralisation of cultured osteoblasts. Infected osteoblasts also increase the expression of RANKL, a key protein involved in initiating bone resorption. None of these effects was seen in a mutant of S. aureus lacking SpA. Complementing the SpA-defective mutant with a plasmid expressing spa or using purified protein A resulted in attachment to osteoblasts, inhibited proliferation and induced apoptosis to a similar extent as wildtype S. aureus. These events demonstrate mechanisms through which loss of bone formation and bone weakening may occur in osteomyelitis patients. This new information may pave the way for the development of new and improved therapeutic agents to treat this disease.
The ability to survive the bactericidal action of serum is advantageous to extraintestinal pathogenic Escherichia coli that gain access to the bloodstream. Evasion of the innate defences present in serum, including complement and antimicrobial peptides, involves multiple factors. Serum resistance mechanisms utilized by E. coli include the production of protective extracellular polysaccharide capsules and expression of factors that inhibit or interfere with the complement cascade. Recent studies have also highlighted the importance of structural integrity of the cell envelope in serum survival. These survival strategies are outlined in this review with particular attention to novel findings and recent insights into well-established resistance mechanisms.
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