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Phagolysosomal Integrity Is Generally Maintained after Staphylococcus aureus Invasion of Nonprofessional Phagocytes but Is Modulated by Strain 6850

Author:
Lâm, Thiên-Trí, Giese, Bernd, Chikkaballi, Deepak, Kühn, Anika, Wolber, Wanja, Pané-Farré, Jan, Schäfer, Daniel, Engelmann, Susanne, Fraunholz, Martin, Sinha, Bhanu
Source:
Infection and immunity 2010 v.78 no.8 pp. 3392-3403
ISSN:
0019-9567
Subject:
Staphylococcus aureus, acidification, hemolysis, humans, pH, phagocytes, phagosomes
Abstract:
Staphylococcus aureus is a major cause of a variety of both local and systemic infections. It can invade human host cells, a process that may account for disseminated and recurrent infections. S. aureus postinvasion events in nonprofessional phagocytes are only partially understood. While morphological data suggest a phagosomal escape, there is a lack of corroborating functional data. Using a combination of pH determination and morphological techniques, we have tested the integrity of Staphylococcus-containing phagosomes in 293 (HEK-293), HeLa, and EA.hy926 cells over time. Rapid acidification of S. aureus-containing phagosomes occurred and was sustained for up to 24 h. All S. aureus strains tested displayed equally sustained intraphagosomal pH levels without exhibiting any correlation with pH level and hemolytic activity. The membrane morphology of the phagosomal compartment was heterogeneous, even under conditions where acidic pH was fully maintained, an observation incompatible with phagolysosomal membrane destruction. As an exception, S. aureus strain 6850 showed a reduced phagosomal acidification signal 6 h after invasion. Additionally, only strain 6850 failed to localize to LAMP-1-positive vesicles in HeLa cells, although this was observed only rarely. Several other strongly beta-hemolytic strains did not modulate phagolysosomal pH, suggesting that S. aureus α-toxin and β-toxin are not sufficient for this process. Taken together, our data suggest that S. aureus-containing phagolysosomes generally remain functionally intact in nonprofessional phagocytes, thereby contrasting with transmission electron micrographic results.
Agid:
285937