A collaboration between researchers at the School of Biochemistry and Immunology and the Department of Microbiology at Trinity College Dublin has identified a mechanism by which the bacterium Staphylococcus aureus (S. aureus) colonizes our nasal passages. The study, published today in the Open Access journal PLOS Pathogens, shows for the first time that a protein located on the bacterial surface called clumping factor B (ClfB) has high affinity for the skin protein loricrin.
S. aureus is a major human pathogen, with the potential to cause severe invasive diseases. It is a major cause for concern in hospitals and healthcare facilities, where many infections are caused by strains resistant to commonly used antibiotics [MRSA]. Interestingly, S. aureus persistently colonizes about 20% of the human population by binding to skin-like cells within the nasal cavity. Being colonized predisposes an individual towards becoming infected so it is vital that we understand the mechanisms involved.
ClfB was previously shown to promote S. aureus colonization in a human nasal colonization volunteer study. This paper now identifies the mechanism by which ClfB facilitates S. aureus nasal colonization. Purified ClfB bound loricrin with high affinity and this interaction was shown to be crucial for successful colonization of the nose in a mouse model. A knockout mouse lacking loricrin in its skin cells allowed fewer bacterial cells to colonize its nasal passages than a normal mouse. When S. aureus strains that lacked ClfB were used nasal colonization could not be achieved at all. Finally it was shown that soluble loricrin could reduce binding of S. aureus to human nasal skin cells and that nasal administration of loricrin reduced S. aureus colonization of mice.
Rachel McLoughlin, the study’s corresponding author and Lecturer at the School of Biochemistry and Immunology at Trinity College Dublin concludes, “Loricrin is a major determinant of S. aureus nasal colonization.” This discovery therefore opens new avenues for developing therapeutic strategies to reduce the burden of nasal carriage and consequently infections with this bacterium. This is particularly important given the difficulties associated with treating MRSA infections.
FINANCIAL DISCLOSURE: This project was funded by a Science Foundation Ireland Programme Investigator award 08/IN.1/B1845 to TJF and a Wellcome Trust RCDF (WT086515MA) to RMM. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
CITATION: Mulcahy ME, Geoghegan JA, Monk IR, O’Keeffe KM, Walsh EJ, et al. (2012) Nasal Colonisation by Staphylococcus aureus Depends upon Clumping Factor B Binding to the Squamous Epithelial Cell Envelope Protein Loricrin. PLOS Pathog 8(12): e1003092. doi:10.1371/journal.ppat.1003092