AbstractStaphylococcus aureus is a major human pathogen which has proved versatile in developing resistance to antimicrobials and acquiring virulence factors. Prior to 1990 methicillin-resistant S. aureus (MRSA) was principally a hospital-acquired pathogen, but in the past two decades there has been the global emergence of community-associated (CA) strains of MRSA. Early reports from the Northern Territory, Australia documented high rates of CA-MRSA in Indigenous people. It is unclear why CA-MRSA has emerged in this setting and what relationship CA-MRSA has with the circulating methicillin-susceptible S. aureus (MSSA) strains.
The epidemiology of S. aureus and CA-MRSA in northern Australia was described by determining population incidences for S. aureus infection and prospectively collecting S. aureus isolates at the Royal Darwin Hospital. The annual incidence of S. aureus bacteraemia was six times higher in the Indigenous compared to the non-Indigenous population. The disease spectra due to CA-MRSA and MSSA were similar. However, remote residence was associated with CA-MRSA.
Irrespective of methicillin-resistance, Panton-Valentine leukocidin (PVL) + isolates appeared more virulent, causing disease in younger, healthier hosts. However, isoforms of PVL conferred no differential clinical effect compared to each other. Diversity was found within the staphylococcal protein A (spa) locus in both CAMRSA and MSSA clonal complex 93 isolates, suggesting multiple independent acquisitions of the methicillin-resistance mediating mecA gene. Molecular typing assays were developed and utilised. These targeted the stable housekeeping genes of the multilocus sequence typing loci, the more rapidly evolving spa locus, and the gene encoding for the pore forming virulence factor PVL. Together, the results support a hypothesis that CA-MRSA has arisen in S. aureus lineages in remote Indigenous communities where staphylococcal disease is highly prevalent. Standard treatment regimens for staphylococcal skin disease may no longer be effective in remote communities and investigations into alternative treatments were commenced.
Note: Please note that Appendix III, IV, V, VI, VII, VIII, X, XI, XII are available in hard copy only.
|Date of Award||Jul 2010|
|Supervisor||Bart Currie (Supervisor), Allen Cheng (Supervisor) & Deborah Holt (Supervisor)|