AbstractStreptococcus pyogenes or group A streptococcus (GAS) is a common human pathogen responsible for a variety of diseases ranging from the uncomplicated common sore throat (pharyngitis), pyoderma (impetigo) to more life threatening conditions such as bacteremia, necrotising fasciitis, and toxic shock like syndrome. Recurrent episodes may lead to serious sequelae such as acute glomerulonephritis (APSGN) and acute rheumatic fever. Streptococcus pyogenes strains may express several distinct fibronectin binding proteins (FBP's) which are considered as major streptococcal adhesins. SfbI a GAS FBP was shown in vitro to promote both adherence and internalisation of the bacterium into host cells and has been implicated in persistence. In the tropical Northern Territory (NT) of Australia, skin and not throat is the major reservoir for isolation of GAS. Recent studies suggest association of NADase in conjunction with streptolysin O a pore forming cytolysin, in subsequent cellular toxicity and tissue destruction in invasive disease. It has also been suggested as an alternate mechanism in GAS inernalisation and subsequent persistence. This thesis investigated the association of FBP's, NADase and streptococcal pyrogenic exotoxins with invasive disease propensity in isolates from bacteremia, necrotising fasciitis and uncomplicated infections. We have used molecular biological tools such as polymerase chain reaction (PCR), southern hybridisation using radiolabelled DNA probes, serological and fluorometric assays on invasive and non-invasive cases from the NT and South Western Sydney (SWS) to screen for these particular phenotypes. The sample isolates included seventy five strains from the NT (INVASIVES = 37, NON-INVASIVE= 38 and 39 from SWS (INV ASIVES = 26, NON-INVASIVE = 13). The results showed that although sfbI the gene for the FBP SfbI implicated in propensity for invasiveness and persistence is found in 60 % of NT isolates there was no significant association with invasive disease and the same was for SWS. Interestingly prtfII although not significant with a p value of 0.0732 showed a trend towards association being represented more often in invasive case isolates. In both the NT and SWS no significant association between NADase production and posession of the three streptococcal pyrogenic exotoxins with invasive disease was found. There was however significantly more expression overall of speC and NADase in SWS than the NT, p = 0.0034, p = 0.0013 respectively. This is interesting, given that the overall crude incidence of severe GAS diseases in the indigenous population of the NT is much higher than SWS. It appears that these results do not directly implicate adhesins, NADase or streptococcal pyrogenic exotoxins with invaisve disease in the NT and SWS.
Note: Please note: Abstract -- "invaisve" was a typographical error from original text.
|Date of Award
|Bart Currie (Supervisor)