Background: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is the causative pathogen in up to 20% of\nstreptococcal-induced infective endocarditis (IE) cases. However, the underlying mechanisms of pathogenesis in S.\ngallolyticus have not yet been solved. Pathogens causing IE need to employ virulent strategies to initiate and\nestablish infections, such as escape the bloodstream, invade the host-cell, and persist intracellularly. In this study,\nwe examined the induction of inflammation by different S. gallolyticus strains in relation to their survival in whole\nblood and cell culture models as well as their ability to induce platelet aggregation. Phagocytosis of these bacteria\nby macrophages, followed by intracellular survival, was also quantified.\nMethods: In whole blood and THP-1 cell culture assays bacterial growth kinetics was determined by plating, followed\nby colony counting. Induction of interleukin (IL)-6 expression in whole blood of three healthy volunteers, caused by\ndifferent strains, was quantified by ELISA. Gene expression of cytokines (IL1B, IL6 and IL8) was quantified by real-time\nPCR after stimulating THP-1 monocytes with bacteria. Induction of platelet aggregation was analyzed by light\ntransmission aggregometry using the BORN method. A macrophage model was used to analyze phagocytosis of\nstrains and their survival in macrophages within 48 h.\nResults: Strains promoted IL-6 secretion in a time-dependent fashion. For example, DSM16831 induced IL-6 secretion\nin whole blood earlier than other isolates, and was eliminated in the whole blood of one volunteer, whereas UCN34\ncould grow. Platelet aggregation depended on the different isolates used and on the individual platelet donor. Two\nstrains (AC1181 and 010672/01) induced cytokine gene expression in THP-1 monocytes only marginally, compared to\nother strains. The phagocytosis rate of S. gallolyticus isolates differed significantly, and the isolates UCN34 and BAA-2069\ncould persist for a considerable time in the phagocytes.\nConclusion: The strain-dependent differences of S. gallolyticus isolates, observed during interaction with human blood\ncells, support the hypotheses that divergences in individual virulence factors determine a distinct pathogenicity of the\nisolates. These data constitute an additional step towards the elucidation of mechanisms in the complex, multifactorial\npathogenesis of this IE pathogen.
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