Peritoneal dialysis (PD) is the dialysis modality of choice for many patients with end-stage renal disease. One of the major complications of therapy is the development of peritonitis, which is associated with significant morbidity and economic costs and may be a contributing factor in the deaths of up to 16% of patients on PD. Even in patients who recover from peritonitis, infections can result in shortened modality survival or modality failure.
Cultures of peritoneal fluid from patients with PD peritonitis have revealed a wide range of causative microbes, both Gram positive and Gram negative. The commonest bacteria identified in a previous study in Western Australia were coagulase negative staphylococci, streptococci, Staphylococcus aureus, enterococci, Pseudomonas aeruginosa, Escherichia coli, Klebsiella and Proteus species.
The peritoneal cavity is covered by a monolayer of mesothelial cells that forms the first line of defence against bacterial invasion. How different bacterial species damage mesothelial cells and influence the biology of the host response is poorly understood. By using pure cultures of bacteria known to cause PD peritonitis as well as mutant strains missing specific proteins or with altered surface properties we will be able to improve our understanding of the mechanism by which different bacterial species and strains damage the mesothelium and influence the resultant cellular response.
Key objectives of this project are:
1. To investigate the in vitro biological effects of bacteria known to cause PD peritonitis on peritoneal mesothelial cells with respect to:
- viability of mesothelial cells
- apoptosis of mesothelial cells
- release of cytokines
- bacterial cell adhesion and migration across a mesothelial layer
- biofilm formation
2. To elucidate the mechanism(s) by which the bacteria induce their effects using mutant bacteria lacking specific virulence factors and heat-killed bacteria.
Data from this project will have direct relevance to improving outcomes for patients with renal failure who are on peritoneal dialysis.
Dr Aron Chakera: [email protected]