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PloS One 2018Streptococcus gallolyticus subsp. gallolyticus is a commensal bacterium of the human gastrointestinal tract, and a pathogen causing infective endocarditis and other...
Streptococcus gallolyticus subsp. gallolyticus is a commensal bacterium of the human gastrointestinal tract, and a pathogen causing infective endocarditis and other biofilm-associated infections via exposed collagen. This study focuses on the characterization of the biofilm formation and collagen adhesion of S. gallolyticus subsp. gallolyticus under different conditions. In this study, it has been observed that the isolate UCN 34 is resistant to 20 mg/ml lysozyme in BHI medium, whereas the strain BAA-2069 builds more biofilm in the presence of lysozyme compared to in a control of BHI without lysozyme. A transcriptome analysis with whole genome microarrays of these two isolates in BHI medium with lysozyme compared to control without lysozyme revealed changes in gene expression levels. In the isolate BAA-2069, 67 genes showed increased expression in the presence of lysozyme, while in the isolate UCN 34, 165 genes showed increased expression and 30 genes showed decreased expression through lysozyme treatment. Products of genes which were higher expressed are in involved in transcription and translation, in cell-wall modification, in hydrogen peroxide resistance and in bacterial immunity. Furthermore, the adhesion ability of different strains of S. gallolyticus subsp. gallolyticus to collagen type I and IV was analyzed. Thereby, we compared the adhesion of 46 human isolates with 23 isolates from animals. It was shown that the adhesion ability depends significantly on whether the isolate was isolated from human or animal. For example, high adhesion ability was observed for strain UCN 34 isolated from an infective endocarditis patient, whereas strain DSM 16831 isolated from koala feces adhered only marginally to collagen. Full genome microarray analysis of these two strains revealed strain-dependent gene expression due to adhesion. The expression of 25 genes of a transposon and 15 genes of a phage region in strain DSM 16831 were increased, which corresponds to horizontal gene transfer. Adherence to collagen in strain UCN 34 led to higher expression of 27 genes and lower expression of 31 genes. This was suggestive of a change in nutrient uptake.
Topics: Biofilms; Muramidase; Streptococcus gallolyticus subspecies gallolyticus; Transcriptome
PubMed: 29373594
DOI: 10.1371/journal.pone.0191705 -
International Journal of Cancer Sep 2017Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC) and its precursors. A previous case-control study...
Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC) and its precursors. A previous case-control study measured antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 and identified significant associations with a small fraction of CRC cases. We aimed at replicating and expanding these findings in an independent study including additional SGG antigens and explored the association with precancerous lesions. We applied multiplex serology to measure antibodies to eleven SGG proteins in serum samples of a screening colonoscopy trial (BliTz study) including participants diagnosed with either non-advanced adenoma (NAA, n = 30), advanced adenoma (AA, n = 100), CRC (n = 50) or controls (n = 228). In addition, we analyzed CRC samples (n = 318) from patients recruited in a clinical setting (DACHSplus study). The association of antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 with CRC was replicated with 4% positive DACHSplus cases compared to 0% positive BliTz controls. Positivity to two or more proteins of a newly defined panel of six SGG markers was significantly associated with CRC in the DACHSplus study (OR: 1.81, 95% CI: 1.07-3.06). Odds for CRC, AA and NAA in the BliTz study were also increased with antibody responses to SGG, and the association was significant for NAA (OR: 2.98, 95% CI: 1.18-7.57). Antibody responses to SGG are associated with CRC and its precursors. The newly identified SGG six-marker panel and associations found with precancerous lesions should be further explored.
Topics: Adenoma; Adult; Aged; Antibodies, Bacterial; Antigens, Bacterial; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Precancerous Conditions; Streptococcal Infections; Streptococcus gallolyticus subspecies gallolyticus
PubMed: 28477334
DOI: 10.1002/ijc.30765 -
IDCases 2022is a gram-positive coccus belonging to the family (SBSEC). Most cases of SBSEC bacteremia are reported in elderly males with underlying hepatobiliary disease and...
is a gram-positive coccus belonging to the family (SBSEC). Most cases of SBSEC bacteremia are reported in elderly males with underlying hepatobiliary disease and associated with infective endocarditis (IE) or colonic malignancy. The gastrointestinal tract is the most common portal of entry, followed by the urinary tract and hepatobiliary tree. We present 5 cases of intrapartum bacteremia caused reported from the labor unit of our hospital from 2019 to 2021. There was histopathological or microbiological evidence of chorioamnionitis in each case. All the mothers were below the age of 35 years, and none of them had underlying hepatobiliary or colonic disease. All maternal antenatal screenings for (GBS) were negative. All the isolates were susceptible to penicillins, ceftriaxone, carbapenems, and vancomycin. Three of them were treated with ceftriaxone and two with aminopenicillins. Duration of treatment varied from 8 days to 14 days. None of the babies were low birth weight or pre-term. All but one baby had clinical sepsis requiring neonatal intensive care unit (NICU) stay, with one having evidence of meningitis and three respiratory distress syndromes (RDS). None of the babies had bacteremia. All mothers and babies made a complete recovery without any complications. These cases suggest that can be a rare but emerging cause of intrauterine infection complicated by post-partum bacteremia. There is possibility of colonization of maternal genital tract with causing neonatal infection.
PubMed: 35815109
DOI: 10.1016/j.idcr.2022.e01562 -
Microbiology Spectrum Dec 2022Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate...
Streptococcus bovisStreptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate platelets is believed to be an important virulence mechanism. While the interactions between bacteria and platelets have been described in detail for many Gram-positive pathogens, little research has been carried out with SBSEC in this respect. Twenty-six isolates of the four most common species and subspecies of SBSEC identified in bacteremia were collected, and interactions with platelets were investigated in platelet rich plasma (PRP) from three donors. Aggregation was studied using light-transmission aggregometry and platelet activation using flow cytometry detecting surface upregulation of CD62P. Platelets and serum were treated with different inhibitors to determine mechanisms involved in platelet aggregation and activation. Twenty-two of 26 isolates induced aggregation in at least one donor, and four isolates induced aggregation in all three donors. In PRP from donor 1, isolate SL1 induced a rapid aggregation with a median time of 70 s to reach 50% aggregation. Blockade of the platelet Fc-receptor or enzymatic cleavage of IgG abolished platelet activation and aggregation. The capacity for bacteria-induced platelet aggregation was also shown to be transferable between donors through serum. SBSEC mediates platelet aggregation in an IgG and IgG-Fc-receptor dependent manner. Bacterial activation of platelets through this pathway is common for many bacteria causing IE and could be a potential therapeutic target for the prevention and treatment of this infection. The capacity of bacteria to activate and aggregate platelets is believed to contribute to the pathogenesis of IE. The Streptococcus bovis/Streptococcus equinus complex (SBSEC) contains known IE-pathogens, but there is limited research on the different subspecies ability to interact with platelets and what signaling pathways are involved. This study reports that 22 of 26 tested isolates of different subspecies within SBSEC can induce aggregation, and that aggregation is host dependent. The Fc-IgG-receptor pathway was shown essential for platelet activation and aggregation. To the best of our knowledge, this is the first study that reports on platelet interactions of SBSEC-isolates other than Streptococcus gallolyticus subspecies as well as the first study to report of mechanisms of platelet interaction of SBSEC-isolates. It adds SBSEC to a group of bacteria that activate and aggregate platelets via the platelet Fc-receptor. This could be a potential therapeutic target for prevention of IE.
Topics: Streptococcus bovis; Platelet Activation; Platelet Aggregation; Blood Platelets; Immunoglobulin G
PubMed: 36374116
DOI: 10.1128/spectrum.01861-22 -
Cureus Feb 2023The diagnosis of infective endocarditis is challenging because it has a variable clinical presentation and nonspecific symptoms and can present in different forms,...
The diagnosis of infective endocarditis is challenging because it has a variable clinical presentation and nonspecific symptoms and can present in different forms, especially when an unusual etiological agent is involved. We present the case of a female in her 70s admitted to the hospital with a medical history of bicytopenia, severe aortic stenosis, and rheumatoid arthritis. She had several consultations during which she presented with asthenia and general malaise. A septic screen test was performed that would determine that was present in a blood culture (BC), which was not valued. About three months later, she was hospitalized. In the first 24 hours of admission, the septic screen test was repeated and was isolated in BC. Splenic infarctions and transthoracic echocardiography suggested probable endocarditis, which was confirmed with transesophageal echocardiography. She underwent surgical intervention to remove the perivalvular abscess and replace the aortic prosthesis.
PubMed: 36879704
DOI: 10.7759/cureus.34529 -
PLoS Pathogens Jul 2017Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been known to have a strong association with colorectal cancer (CRC). This knowledge has important clinical...
Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been known to have a strong association with colorectal cancer (CRC). This knowledge has important clinical implications, and yet little is known about the role of Sg in the development of CRC. Here we demonstrate that Sg promotes human colon cancer cell proliferation in a manner that depends on cell context, bacterial growth phase and direct contact between bacteria and colon cancer cells. In addition, we observed increased level of β-catenin, c-Myc and PCNA in colon cancer cells following incubation with Sg. Knockdown or inhibition of β-catenin abolished the effect of Sg. Furthermore, mice administered with Sg had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin staining in colonic crypts compared to mice receiving control bacteria. Finally, we showed that Sg is present in the majority of CRC patients and is preferentially associated with tumor compared to normal tissues obtained from CRC patients. These results taken together establish for the first time a tumor-promoting role of Sg that involves specific bacterial and host factors and have important clinical implications.
Topics: Animals; Colorectal Neoplasms; Disease Progression; Female; Humans; Mice; Signal Transduction; Streptococcal Infections; Streptococcus gallolyticus subspecies gallolyticus; beta Catenin
PubMed: 28704539
DOI: 10.1371/journal.ppat.1006440 -
PloS One 2015Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus subsp. gallolyticus), a member of group D streptococci, is an inhabitant of the animal and human...
Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus subsp. gallolyticus), a member of group D streptococci, is an inhabitant of the animal and human gastrointestinal tract. Furthermore, it is a facultative pathogen which causes e.g. endocarditis, septicemia and mastitis. S. gallolyticus subsp. gallolyticus may be transmitted either directly or indirectly between animals and humans. However, the transmission routes are an unsolved issue. In this study, we present systematic analyses of an S. gallolyticus subsp. gallolyticus isolate of an infective endocarditis patient in relation to isolates of his laying hen flock. Isolates from pooled droppings of laying hens, pooled dust samples and human blood culture were characterized by using multilocus sequence typing (MLST) and DNA fingerprinting. MLST revealed the same allelic profile of isolates from the human blood culture and from the droppings of laying hens. In addition, these isolates showed clonal identity regarding a similar DNA fingerprinting pattern. For the first time, we received a hint that transmission of S. gallolyticus subsp. gallolyticus between poultry and humans may occur. This raises the question about the zoonotic potential of isolates from poultry and should be considered in future studies.
Topics: Animals; Bacterial Proteins; Chickens; Endocarditis, Bacterial; Feces; Humans; Male; Middle Aged; Multilocus Sequence Typing; Streptococcal Infections; Streptococcus
PubMed: 25978355
DOI: 10.1371/journal.pone.0126507 -
PLoS Pathogens Oct 2022Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon...
Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. Previous work showed that this organism stimulates CRC cells proliferation and tumor growth. However, the molecular mechanisms underlying these activities are not well understood. Here, we found that Sgg upregulates the expression of several type of collagens in HT29 and HCT116 cells, with type VI collagen (ColVI) being the highest upregulated type. Knockdown of ColVI abolished the ability of Sgg to induce cell proliferation and reduced the adherence of Sgg to CRC cells. The extracellular matrix (ECM) is an important regulator of cell proliferation. Therefore, we further examined the role of decellularized matrix (dc-matrix), which is free of live bacteria or cells, in Sgg-induced cell proliferation. Dc-matrix prepared from Sgg-treated cells showed a significantly higher pro-proliferative activity than that from untreated cells or cells treated with control bacteria. On the other hand, dc-matrix from Sgg-treated ColVI knockdown cells showed no difference in the capacity to support cell proliferation compared to that from untreated ColVI knockdown cells, suggesting that the ECM by itself is a mediator of Sgg-induced cell proliferation. Furthermore, Sgg treatment of CRC cells but not ColVI knockdown CRC cells resulted in significantly larger tumors in vivo, suggesting that ColVI is important for Sgg to promote tumor growth in vivo. These results highlight a dynamic bidirectional interplay between Sgg and the ECM, where Sgg upregulates collagen expression. The Sgg-modified ECM in turn affects the ability of Sgg to adhere to host cells and more importantly, acts as a mediator for Sgg-induced CRC cell proliferation. Taken together, our results reveal a novel mechanism in which Sgg stimulates CRC proliferation through modulation of the ECM.
Topics: Cell Proliferation; Collagen Type VI; Colorectal Neoplasms; Extracellular Matrix; Humans; Streptococcus gallolyticus subspecies gallolyticus
PubMed: 36191045
DOI: 10.1371/journal.ppat.1010894 -
Scientific Reports Apr 2023Streptococcus gallolyticus subspecies gallolyticus (Sgg) is known to be strongly associated with colorectal cancer (CRC). Recent functional studies further demonstrated...
Streptococcus gallolyticus subspecies gallolyticus (Sgg) is known to be strongly associated with colorectal cancer (CRC). Recent functional studies further demonstrated that Sgg actively stimulates CRC cell proliferation and promotes the development of colon tumors. However, the Sgg factors important for the pro-proliferative and pro-tumor activities of Sgg remain unclear. Here, we identified a chromosomal locus in Sgg strain TX20005. Deletion of this locus significantly reduced Sgg adherence to CRC cells and abrogated the ability of Sgg to stimulate CRC cell proliferation. Thus, we designate this locus as the Sgg pathogenicity-associated region (SPAR). More importantly, we found that SPAR is important for Sgg pathogenicity in vivo. In a gut colonization model, mice exposed to the SPAR deletion mutant showed significantly reduced Sgg load in the colonic tissues and fecal materials, suggesting that SPAR contributes to the colonization capacity of Sgg. In a mouse model of CRC, deletion of SPAR abolished the ability of Sgg to promote the development of colon tumors growth. Taken together, these results highlight SPAR as a critical pathogenicity determinant of Sgg.
Topics: Animals; Mice; Streptococcus gallolyticus subspecies gallolyticus; Virulence; Colorectal Neoplasms; Colonic Neoplasms; Streptococcal Infections
PubMed: 37072463
DOI: 10.1038/s41598-023-33178-z -
BMC Microbiology Oct 2017Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is the causative pathogen in up to 20% of streptococcal-induced infective endocarditis (IE) cases....
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.
METHODS
In 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.
RESULTS
Strains 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.
CONCLUSION
The 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.
Topics: Cell Line, Tumor; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Interleukins; Macrophages; Platelet Aggregation; Species Specificity; Streptococcal Infections; Streptococcus gallolyticus subspecies gallolyticus; THP-1 Cells
PubMed: 29078765
DOI: 10.1186/s12866-017-1116-1