AbstractThe pathogen Streptococcus pyogenes (group A streptococcus, GAS) is the causative agent of numerous human diseases. It can be carried asymptornatically, or may cause a variety of clinical syndromes including pharyngitis and pyoderma, and severe invasive diseases such as necrotising fasciitis and toxic shock syndrome. Whereas less severe infections are generally self-limiting, the sequelae of GAS infection are potentially life threatening. The two major non-suppurative sequelae are acute poststreptococcal glomeruloncphritis (APSGN) and acute rheumatic fever (ARF).
The binding of bacterial cell surface adhesins to host receptor molecules is one of the most critical steps in microbial colonisation and pathogenesis. In GAS, attachment requires many adhesins including M protein, lipoteichoic acid and fibronectin binding proteins (FBPs). Of these, FBPs are known to be major contributors to adhesion.
The aim of this study is to develop an anti-adhesion strategy to inhibit the attachment of GAS to host cells, thereby preventing colonisation and subsequent infection. In our study we aim to use synthetic peptides corresponding to one of the streptococcal FBPs to block the attachment of GAS to host cells. This approach is not expected to interfere with the body's normal flora as the peptide would bind specifically to the GAS receptor on the host cell. It is hypothesised that prevention of GAS attachment to skin or throat cells in turn will prevent the establishment of infection.
Fifty six percent of NT GAS isolates tested in this study contained the gene for SfbI, a major GAS FBP. A peptide (peptide MSG) based on this adhesin inhibits fibronectin-binding by the pathogen. To test whether this peptide also blocks attachment of GAS to host cells adhesion assay were performed with strains possessing different combinations of genes for three distinct FBPs, including SfbI. This peptide successfully inhibited attachment of 40% of GAS isolates tested.Success of this inhibition was not associated with the number of FBP genes encoded by the isolate or by its fibronectin binding capacity, but appears to be dependent upon the individual GAS isolate and the target host cell. In summary,this approach has proven successful and further investigation will tell us whether the peptide tested is likely to be an effective prophylactic measure for GAS infection in this population.
|Date of Award||2004|
|Supervisor||Peter Fagan (Supervisor) & Bart Currie (Supervisor)|
Anti-attachment peptides: a novel therapeutic strategy to control group A streptococcal infection in the Northern Territory of Australia
Kennedy, M. L. (Author). 2004
Student thesis: Masters by Research - CDU