In vitro ability of Staphylococcus aureus isolates from bacteraemic patients with and without metastatic complications to invade vascular endothelial cells

Abstract

Invasion of vascular endothelial cells is thought to be a critical step in the development of metastatic infections in patients with Staphylococcus aureus bacteraemia. This study was designed to evaluate the association between the ability to invade endothelial cells and metastatic infection by S. aureus. Patients with metastatic infection were identified among those with community-acquired S. aureus bacteraemia in a tertiary referral hospital. Patients with simple bacteraemia caused by S. aureus over the same period served as the control group. The ability of each clinical isolate to invade endothelial cells was evaluated by counting the number of intracellular organisms 1 h after inoculation onto human umbilical vein endothelial cells in vitro. The cytotoxic activity of intracellular S. aureus was determined 24 h after internalization, and expressed as the percentage of cells killed. The clinical isolates varied in invasiveness and cytotoxicity. The median invasiveness, relative to S. aureus reference strain ATCC 29213, was 145 % in the cases (n510) [interquartile range (IQR) 103-160] and 153 % in the controls (n511; P50.44). The median cytotoxicity was 59.4 % (IQR 47-68) in the cases and 65.2 % (IQR 50-74) in the controls (P50.44). Differences in the ability of S. aureus to invade and destroy vascular endothelial cells in vitro were not associated with the development of metastatic complications in patients with S. aureus bacteraemia. This implies that the invasiveness and toxicity of S. aureus for endothelial cells may not be major determinants of metastatic infection. INTRODUCTIONStaphylococcus aureus is an important cause of severe community-acquired and nosocomial bacteraemia (Weinstein et al., 1997). A major complication of S. aureus bacteraemia is the development of metastatic infection. The reported frequency of metastatic infection following S. aureus bacteraemia varies from 2 to 47 % (Lautenschlager et al., 1993;Willcox et al., 1998;Mylotte et al., 1987;Nolan & Beaty, 1976;Cunney et al., 1996;Finkelstein et al., 1984).The most common sites of metastatic foci include cardiac valve, bone and joints, lung, kidney, central nervous system and skin (Lautenschlager et al., 1993;Julander, 1985;Nolan & Beaty, 1976;Mirimanoff & Glauser, 1982). Metastatic complications in S. aureus bacteraemia are clinically important because they are associated with recurrent infection and grave outcome (Musher et al., 1994;Lautenschlager et al., 1993;Julander, 1985).Although little is known about the pathogenesis of metastatic complications in S. aureus bacteraemia, it is thought that interaction between vascular endothelial cells and circulating bacteria is a first step in the extravasation of S. aureus (Lowy, 1998). Many studies have shown that S. aureus bacteria attach avidly to and invade vascular endothelial cells (Vercellotti et al., 1984;Ogawa et al., 1985). After invasion, the infected endothelial cells express Fc receptors and adhesion molecules, and then release interleukin-1, interleukin-6 and interleukin-8. This ...

In vitro characterization of representative clinical South African Staphylococcus aureus isolates from various clonal lineages

“…Park et al . investigated if any association was present between cytotoxicity of clinical S. aureus isolates and their abilities to cause metastatic infections . They found that the ability to induce host cell death and be cytotoxic to endothelial cells was not a major determinant of metastatic infections.…”

Cellular Pharmacodynamics of the Novel Biaryloxazolidinone Radezolid: Studies with Infected Phagocytic and Nonphagocytic cells, UsingStaphylococcus aureus,Staphylococcus epidermidis,Listeria monocytogenes, andLegionella pneumophila

“…We also assessed the intracellular activity of radezolid against different strains of S. aureus with various resistance mechanisms, including to linezolid. Finally, we used different cell types as models of territories where S. aureus can survive intracellularly (endothelial cells, osteoblasts, respiratory epithelial cells, keratinocytes, and fibroblasts [11,14,22,36,41]), together with phagocytic cells (macrophages).…”

Staphylococcal Sepsis and Frequency of Metastatic Foci

“…Staphylococcal sepsis are in most cases accompanied by metastatic foci in various organ systems. Most commonly affected organs are the heart valves, bones and joints, lungs, kidneys, central nervous system, skin and soft tissue (12). The study of Fowler and colleagues (7) showed that, among other metastatic complications 89 patients had endocarditis 54 septic arthritis and meningitis 12.…”