2020-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/701635In Taiwan, over million central venous access devices are placed annually in clinical practice. Adequate catheter function and hygiene are important in providing treatment for patients with end-stage renal disease or delivering chemotherapy drugs. The catheter-related sheaths may cause catheter occlusion and central line dysfunction. The pathogenesis of catheter-related sheaths remains unknown. However, the histological findings showed prominent migration and proliferation of vascular smooth muscle cells in the sheath structure. Neutrophils, the most abundant innate immune effector cells, are the first line of defense against microbes. Neutrophils may utilize phagocytosis or form neutrophil extracellular traps (NETs) to cope the bacteria. In our preliminary data, we found 16S rRNA and NETs in clinical specimens of catheter-related sheaths while staphylococcus aureus is the most common pathogen. In our rat central venous catheterization model, we successfully mimic the phenomenon of sheath formation surrounding the catheter. Detection of NETs and smooth muscle cell proliferation was found in catheter-related sheaths in rats. Intravenous bacteria injection intensified sheath thickness and digestion of NETs by DNase I alleviated the severity of bacteria-induced sheath formation. In contrast, intravenous antibiotic treatment did not influence the sheath formation. Isogenic mutant strains deficient in staphylococcal two component system (TCS), Δ saeSR, ΔarlSR, ΔvraSR, showed reduced ability to form biofilm and to resist neutrophil phagocytosis. The isogenic mutant strain, ΔsaeSR, reduced the thickness of sheath and formation of NETs in catheter-related sheath in rat catheterization model. Based on these findings, we aim to investigate the regulation of two component systems in staphylococcus aureus and its influence on neutrophil evasion and NETs in catheter-related sheath formation as well as its pathogenesis and possible therapeutic strategy.catheter-related sheathneutrophilneutrophil extracellular trapsstaphylococcus aureustwo component system