Strain-dependent interactions of Streptococcus gallolyticus subsp. gallolyticus with human blood cells

Abstract

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

Platelet Activation and Aggregation Induced by Streptococcus bovis / Streptococcus equinus Complex

“…Many isolates induced aggregation in one or two donors but not all three, suggesting that aggregation is not only a matter of bacterial properties, but also dependent on host factors. This is consistent with previous findings about aggregation induced by Sg gallolyticus ( 28 ). To determine which host factors are of importance, a larger study with more donors would be required.…”

“…For SBSEC, there is limited research regarding the interactions with platelets. Veloso et al ( 27 ) showed that a strain of Sg gallolyticus induced platelet aggregation, and a study by Grimm et al ( 28 ) suggested that aggregation is both host and isolate dependent. However, no studies have investigated which host and bacterial factors are important for this interaction.…”

Isolation, characterization, and experimental infection of Streptococcus gallolyticus subspecies pasteurianus from commercial turkeys with acute septicemia: a pilot study

“…Other studies have also confirmed that both high- and low-virulence strains can adhere to the intestinal mucosa, ensuring that adhesion to enterocytes and intracellular cell proliferation are key factors in the pathogenesis of SG ( Kimpe et al, 2003 ; Abranches et al, 2011 ; Kumar et al, 2022 ). Interestingly, the induction of inflammation by different SG strains was associated with their intracellular survivability in red blood cells and macrophages ( Grimm et al, 2017 ). To better understand this potential mechanism, it is important to consider the general pathogenesis of Streptococcus infections and the specifics of SG infection in turkeys, as demonstrated in humans previously.…”

Comparative analysis of 31 Streptococcus gallolyticus strains uncovers their potential risks from the perspectives of virulence factors and antibiotic resistance genes

“…Besides, S. gallolyticus possesses a unique virulence factor that promotes infection in susceptible individuals and depends on pre-existing colonic abnormalities [13]. The unique pathogenicity of S. gallolyticus isolates was determined by the difference of individual virulence factors during the interaction between dependent differences and human blood cells, which constitute further elucidating the mechanisms in the complex pathogenesis of the IE pathogen [14]. However, the understanding of antibiotic resistance and virulence factors is limited and the pathogenesis of infection remains elusive.…”