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 December 28 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.
Journal Reference:
- Mulcahy ME, Geoghegan JA, Monk IR, O'Keeffe KM, Walsh EJ, et al. Nasal Colonisation by Staphylococcus aureus Depends upon Clumping Factor B Binding to the Squamous Epithelial Cell Envelope Protein Loricrin. PLOS Pathog, 2012 DOI: 10.1371/journal.ppat.1003092
Courtesy: ScienceDaily
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