Intracellular fate of Staphylococcus aureus in human phagocytic and non-phagocytic cells and role of virulence factors
(2008)
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- The intracellular survival of S. aureus is believed to contribute to the recurrence of some staphylococcal infections such as endocarditis or osteomyelitis. Previous publications reported the ability of this pathogen to colonize multiple cell types. However the precise fate of intracellular S. aureus is still poorly understood. Here we examine the intracellular development of S. aureus in two human cell types, the THP-1 macrophages and HUVEC endothelial cells. We compare the internalization, intracellular growth and intracellular location in both cell types after 24h of infection as well as the activity of antibiotics against intracellular bacteria. S. aureus expresses a wide range of virulence factors; some of them are most probably required for intracellular survival. Hence, we studied the implication of phosphatase rsbU and the alternative transcription factor sigmaB involved in stress response and investigated the role of three membrane-damaging toxins (alpha-, beta- and gamma-hemolysins) on the development of intracellular infection. Internalization was more efficient in THP-1 but, once inside the cells, S. aureus proliferated and reached similar intracellular growth in both cells types. After 24h of infection in THP-1, S. aureus was confined in phagolysosomes but was able to multiply actively in this acidic environment. In HUVEC bacteria were localized in acidic compartments and in the cytoplasm. Oxacillin, gentamicin, vancomycin and oritavancin showed a high activity in broth but the first three drugs had a poor activity against intracellular S. aureus which was similar in both cell types. Only oritavancin displayed a high intracellular activity close to 3 log decrease from initial inoculum. The alpha-, beta-, and gamma-hemolysins did not seem to contribute to the development of intracellular infection. In contrast, the presence of a functional phosphatase rsbU and a subsequent efficient regulation of the transcription factor sigmaB confered an advantage in terms of internalization, intracellular growth and resistance to hydrogen peroxide. This higher intracellular growth and resistance to H2O2 is related to the important production of the golden pigment staphyloxanthin, which seems to confer a significant advantage for intracellular survival.
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Olivier, A. (2008). Intracellular fate of Staphylococcus aureus in human phagocytic and non-phagocytic cells and role of virulence factors. https://hdl.handle.net/2078.5/98064