Survival of S. aureus within host cells was also reported in tissues and other cell types. For instance, Tuchscherr et al. reported that S. aureus could persist within host cells and/or tissues for several weeks [36], survive within human lung epithelial cells for up to 2 weeks [37], persist in macrophage vacuoles for 3–4 days before escaping into the cytoplasm and causing macrophage lysis [6], and remain viable for up to MDV3100 research buy 5 days within HT-29 and Caco-2 enterocytes [38]. It was proposed that, once inside osteoblasts, macrophages, or

other cells, S. aureus may undergo phenotypic switching to small colony variants (SCVs), which are associated with increased anchoring of fibronectin-binding proteins and clumping factors on the bacterial surface [36,39]. These proteins may function as substrates for bacterial enzymes that are needed to evade phagocytic oxidative killing [6,40] thereby contributing to the intracellular survival of S. aureus. Moreover, S. aureus produces catalase, which catalyzes the GSK1120212 in vitro decomposition of H2O2, thereby protecting itself inside host cells such as macrophages [41]. It was believed that the phenotypic switching of S. aureus may make the bacteria more resistant to antibiotics [17,42]. Similarly, S. epidermidis was found to persist in macrophages and also in peri-implant tissues Capmatinib in mice despite antibiotic treatments [43,44]. The survival

of S. aureus within cells like macrophages and osteoblasts and the possible phenotypic switching of S. aureus may explain why Edoxaban antibiotics have so often failed to cure Staphylococcal infections [2,17,36]. In addition, the presence of antibodies (e.g. anti-tumor necrosis factor-related apoptosis-inducing ligand or TRAIL antibody) may improve the viability of infected host cells and provide better protection

for the intra-cellular bacteria [45]. Alexander et al. found that in the presence of 1 μg/mL of anti-TRAIL antibody, the percentage of apoptotic cells decreased from the control (in the absence of antibody) of 32% to 28% [45]. Future studies may focus on investigation of the possible changes that occur to S. aureus after internalization into osteoblasts and macrophages and the effect of a variety of opsonins potentially present in vivo. This study was limited to in vitro cell studies which may not reflect what is happening in patients with chronic infections. In vivo studies using chronic infection animal models, which may allow monitoring of intracellular presence of S. aureus with time, are needed in the future. S. aureus infection also resulted in significantly increased levels of H2O2 in infected osteoblasts at infection times of 0.5 and 1 h and in infected macrophages at infection time of 1 h. The O. 2 − levels in infected macrophages significantly increased at infection times of 0.5 and 1 h. The increase in reactive oxygen species indicates that S.