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Enfermedades Infecciosas Y... Apr 2023Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The...
INTRODUCTION
Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes.
METHODS
Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes.
RESULTS
There are significant differences between the incidence of SBEC IE in HL (27.9/10) vs. HF and HB (8.8 and 7,1, respectively, p<0.001). We found significant differences (SbI vs. SbII) in mean age (68.5 vs. 73 years; p<0.01), duration of symptoms before diagnosis (46.9±46.5 vs. 30.4±40.9 days; p<0.01), presence of comorbidities: 39.1% (78) vs. 54.2% (32; p<0.04), predisposing heart illness:62.3% (124) vs. 81.3% (48; p<0.006), particularly, prosthetic or intravascular devices IE: 24.6% (49) vs. 52.4% (31; p<0.001), bi-valve involvement:23.6% (47) vs. 11.8% (7; p<0.05) and heart failure: 24.6% (49) vs. 38.9% (23; p<0.03). There were no significant differences in embolic events, need for surgery or mortality. The association with CRC was high in both groups: 77.7% vs. 66.6%.
CONCLUSIONS
IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high.
Topics: Adult; Humans; Streptococcus bovis; Retrospective Studies; Streptococcal Infections; Endocarditis, Bacterial; Endocarditis
PubMed: 36610830
DOI: 10.1016/j.eimce.2021.08.017 -
BMC Research Notes Oct 2022Clinical outcomes of infection by S. gallolyticus have not been investigated extensively. We aimed to determine the prevalence of S. gallolyticus in tumor specimens...
OBJECTIVE
Clinical outcomes of infection by S. gallolyticus have not been investigated extensively. We aimed to determine the prevalence of S. gallolyticus in tumor specimens obtained from Iranian patients diagnosed with colorectal cancer. Polymerase chain reaction was used to confirm the presence of S. gallolyticus in patients' tissue samples.
RESULTS
Of 176 patients, 65 were diagnosed with colorectal cancer whereas 111 did not have any colon disease. No correlation was found between age, colonization with S. gallolyticus, gender, or risk factors. Overall, 72 (40%) patients carried S. gallolyticus; only 29% of the patients without colorectal cancer were positive for S. gallolyticus. Diagnosis of colorectal cancer and presence of S. gallolyticus significantly correlated (P = 0.006; odds ratio = 1.46; 95% CI = 1.21-3.87). Among the patients with colorectal cancer, 39 (60%) were positive with S. gallolyticus (P = 0.006) whereas 33 of 111 (29.7%) control subjects were positive for S. gallolyticus (P > 0.05); thus, 70.3% of the control subjects were not infected with S. gallolyticus. We found a high prevalence of S. gallolyticus among an Iranian cohort of patients with colorectal cancer. Despite previous reports, we report a positive correlation between colorectal cancer and S. gallolyticus colonization.
Topics: Colorectal Neoplasms; Humans; Iran; Odds Ratio; Streptococcal Infections; Streptococcus gallolyticus
PubMed: 36199123
DOI: 10.1186/s13104-022-06207-9 -
Frontiers in Cellular and Infection... 2022subspecies () is an opportunistic pathogen causing invasive infections in the elderly often associated with colon neoplasia. The prevalence of in the stools of...
PURPOSE
subspecies () is an opportunistic pathogen causing invasive infections in the elderly often associated with colon neoplasia. The prevalence of in the stools of patients with normal colonoscopy (control) was compared with patients with colorectal adenomas (CRA) or with carcinomas (CRC) from stages I to IV. The presence of the s island encoding colibactin as well as other CRC-associated bacteria such as toxicogenic , , and was also investigated.
PATIENTS AND METHODS
Fecal samples collected in France between 2011 and 2016 from patients with normal colonoscopy ( = 25), adenoma ( = 23), or colorectal cancer at different stages ( = 81) were tested by PCR for the presence of , , , , and the island. Relative quantification of , , and in stools was performed by qPCR.
RESULTS
prevalence was significantly increased in the CRC group. Our results also revealed i) a strong and significant increase of toxinogenic in patients with early-stage adenoma and of island at late-stage CRC and ii) increased levels of and in the stools of CRC patients. Furthermore, the simultaneous detection of these five bacterial markers was only found in CRC patients.
CONCLUSIONS
Our results indicate that the prevalence or relative levels of CRC-associated bacteria vary during CRC development. Among them, (+) was singled out as the sole pathobiont detected at the early adenoma stage.
Topics: Aged; Bacteria; Bacterial Infections; Bacteroides fragilis; Carcinoma; Humans; Streptococcus gallolyticus
PubMed: 35360109
DOI: 10.3389/fcimb.2022.794391 -
Microbiology Spectrum Aug 2023Streptococcus gallolyticus subsp. () is an opportunistic bacterial pathogen strongly associated with colorectal cancer. Here, through comparative genomics analysis, we...
Streptococcus gallolyticus subsp. () is an opportunistic bacterial pathogen strongly associated with colorectal cancer. Here, through comparative genomics analysis, we demonstrated that the genetic locus encoding the type VIIb secretion system (T7SSb) machinery is uniquely present in in two different arrangements. UCN34 carrying the most prevalent T7SSb genetic arrangement was chosen as the reference strain. To identify the effectors secreted by this secretion system, we inactivated the gene encoding the motor of this machinery. A comparison of the proteins secreted by UCN34 wild type and its isogenic Δ mutant revealed six T7SSb effector proteins, including the expected WXG effector EsxA and three LXG-containing proteins. In this work, we characterized an LXG-family toxin named herein TelE promoting the loss of membrane integrity. Seven homologs of TelE harboring a conserved glycine zipper motif at the C terminus were identified in different isolates. Scanning mutagenesis of this motif showed that the glycine residue at position 470 was crucial for TelE membrane destabilization activity. TelE activity was antagonized by a small protein TipE belonging to the DUF5085 family. Overall, we report herein a unique T7SSb effector exhibiting a toxic activity against nonimmune bacteria. In this study, 38 clinical isolates of Streptococcus gallolyticus subsp. () were sequenced and a genetic locus encoding the type VIIb secretion system (T7SSb) was found conserved and absent from 16 genomes of the closely related S. gallolyticus subsp. (). The T7SSb is a bona fide pathogenicity island. Here, we report that the model organism strain UCN34 secretes six T7SSb effectors. One of the six effectors named TelE displayed a strong toxicity when overexpressed in Escherichia coli. Our results indicate that TelE is probably a pore-forming toxin whose activity can be antagonized by a specific immunity protein named TipE. Overall, we report a unique toxin-immunity protein pair and our data expand the range of effectors secreted through T7SSb.
Topics: Streptococcus gallolyticus subspecies gallolyticus; Amino Acid Motifs; Glycine; Type VII Secretion Systems
PubMed: 37432124
DOI: 10.1128/spectrum.01481-23 -
BMC Infectious Diseases Nov 2021Bacteremia due to the Streptococcus bovis/Streptococcus equinus complex (SBSEC) is associated with specific diseases, such as colorectal cancer and infective...
Laboratory identification and clinical characteristics of Streptococcus bovis/Streptococcus equinus complex bacteremia: a retrospective, multicenter study in Hiroshima, Japan.
BACKGROUND
Bacteremia due to the Streptococcus bovis/Streptococcus equinus complex (SBSEC) is associated with specific diseases, such as colorectal cancer and infective endocarditis. This study aimed to evaluate the clinical characteristics of SBSEC bacteremia and the accuracy of identification of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and phenotypic identification systems for SBSEC isolates.
METHODS
We analyzed patients with SBSEC bacteremia retrospectively between 2012 and 2019 at three hospitals in Japan. We re-identified each SBSEC isolate using sequencing superoxide dismutase (sodA) analysis, MALDI-TOF MS using the MALDI Biotyper, and phenotypic identification using the VITEK2.
RESULTS
During the study period, 39 patients with SBSEC bacteremia were identified. S. gallolyticus subsp. pasteurianus (SGSP, n = 29), S. gallolyticus subsp. gallolyticus (SGSG, n = 5), S. lutetiensis (SL, n = 4), and S. infantarius subsp. infantarius (n = 1) were identified using sodA sequencing analysis. Primary bacteremia (36%) was the most common cause of bacteremia, followed by infective endocarditis (26%) and biliary tract infections (23%). Colorectal cancer was associated significantly with SGSG bacteremia, while the sources of bacteremia were similar in each SBSEC subspecies. The MALDI Biotyper was significantly more accurate in identifying the SBSEC isolates at the subspecies level compared to the VITEK2 (92% vs. 67%, P = 0.010). In contrast, there were no significant differences in the rates of correct identification of the SBSEC isolates at the species level between the MALDI Biotyper and the VITEK2 (100% vs. 87%, P = 0.055).
CONCLUSIONS
Bacteremia with SGSG was associated with colorectal cancer, and the sources of bacteremia were similar in each SBSEC subspecies. The MALDI-TOF MS was significantly more accurate in identifying SBSEC isolates at the subspecies level than the phenotypic identification systems. The accurate identification of SBSEC isolates using the MALDI-TOF MS and phenotypic identification systems was sufficient at the species level, but it was insufficient at the subspecies level. Therefore, it may be reasonable for clinicians to perform echocardiographies and colonoscopies in all patients with SBSEC bacteremia.
Topics: Bacteremia; Humans; Japan; Laboratories; Retrospective Studies; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptococcal Infections; Streptococcus bovis
PubMed: 34836500
DOI: 10.1186/s12879-021-06880-4 -
Diagnostic Microbiology and Infectious... Nov 2023To develop an in-house matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) library for improved identification of species and...
OBJECTIVES
To develop an in-house matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) library for improved identification of species and subspecies of the Streptococcus bovis/Streptococcus equinus-complex (SBSEC).
METHODS
A total of 236 SBSEC isolates from blood stream infections and culture collections, determined by whole genome sequencing to subspecies level, were grown in brain heart infusion broth. Mass spectra were collected using the Bruker MALDI Biotyper system after ethanol-formic acid extraction. Main spectral profiles from 117 isolates were used to create the "SBSEC-CMRS library." The remaining 119 spectra were used for evaluation of Bruker MALDI Biotyper (MBT) Compass Library Revision K (2022) and the SBSEC-CMRS library.
RESULTS
The Bruker library correctly identified species and subspecies in 72 of 119 (61 %) isolates, while the SBSEC-CMRS library identified 116 of 119 (97 %), using a cutoff score of ≥2.0.
CONCLUSIONS
The SBSEC-CMRS library showed sufficient diagnostic accuracy, and can be implemented in clinical practice for SBSEC species and subspecies identification.
Topics: Humans; Streptococcus bovis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptococcus
PubMed: 37598592
DOI: 10.1016/j.diagmicrobio.2023.116045 -
PloS One 2023Streptococcus gallolyticus sp. gallolyticus (SGG) is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher SGG contribution in tumor...
Streptococcus gallolyticus sp. gallolyticus (SGG) is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher SGG contribution in tumor initiation and/or acceleration respectively, a global transcriptome was performed in human normal colonic cells (FHC) and in human tumoral colonic cells (HT29). To identify SGG-specific alterations, we chose the phylogenetically closest relative, Streptococcus gallolyticus subsp. macedonicus (SGM) as control bacterium. We show that SGM, a bacterium generally considered as safe, did not induce any transcriptional changes on the two human colonic cells. The transcriptional reprogramming induced by SGG in normal FHC and tumoral HT29 cells was significantly different, although most of the genes up- and down-regulated were associated with cancer disease. Top up-regulated genes related to cancer were: (i) IL-20, CLK1, SORBS2, ERG1, PIM1, SNORD3A for normal FHC cells and (ii) TSLP, BHLHA15, LAMP3, ZNF27B, KRT17, ATF3 for cancerous HT29 cells. The total number of altered genes were much higher in cancerous than in normal colonic cells (2,090 vs 128 genes being affected, respectively). Gene set enrichment analysis reveals that SGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest that SGG induces a pro-tumoral shift in human colonic cells particularly in transformed cells potentially accelerating tumor development in the colon.
Topics: Humans; Streptococcus gallolyticus subspecies gallolyticus; Colorectal Neoplasms; Streptococcus; Gene Expression Profiling; Streptococcal Infections; Streptococcus gallolyticus
PubMed: 38033043
DOI: 10.1371/journal.pone.0294868 -
Scientific Reports Jun 2024Streptococcus gallolyticus (Sg) is a non-motile, gram-positive bacterium that causes infective endocarditis (inflammation of the heart lining). Because Sg has gained...
Integration of molecular docking and molecular dynamics simulations with subtractive proteomics approach to identify the novel drug targets and their inhibitors in Streptococcus gallolyticus.
Streptococcus gallolyticus (Sg) is a non-motile, gram-positive bacterium that causes infective endocarditis (inflammation of the heart lining). Because Sg has gained resistance to existing antibiotics and there is currently no drug available, developing effective anti-Sg drugs is critical. This study combined core proteomics with a subtractive proteomics technique to identify potential therapeutic targets for Sg. Several bioinformatics approaches were used to eliminate non-essential and human-specific homologous sequences from the bacterial proteome. Then, virulence, druggability, subcellular localization, and functional analyses were carried out to specify the participation of significant bacterial proteins in various cellular processes. The pathogen's genome contained three druggable proteins, glucosamine-1phosphate N-acetyltransferase (GlmU), RNA polymerase sigma factor (RpoD), and pantetheine-phosphate adenylyltransferase (PPAT) which could serve as effective targets for developing novel drugs. 3D structures of target protein were modeled through Swiss Model. A natural product library containing 10,000 molecules from the LOTUS database was docked against therapeutic target proteins. Following an evaluation of the docking results using the glide gscore, the top 10 compounds docked against each protein receptor were chosen. LTS001632, LTS0243441, and LTS0236112 were the compounds that exhibited the highest binding affinities against GlmU, PPAT, and RpoD, respectively, among the compounds that were chosen. To augment the docking data, molecular dynamics simulations and MM-GBSA binding free energy were also utilized. More in-vitro research is necessary to transform these possible inhibitors into therapeutic drugs, though computer validations were employed in this study. This combination of computational techniques paves the way for targeted antibiotic development, which addresses the critical need for new therapeutic strategies against S. gallolyticus infections.
Topics: Molecular Docking Simulation; Proteomics; Molecular Dynamics Simulation; Bacterial Proteins; Anti-Bacterial Agents; Streptococcus gallolyticus; Humans
PubMed: 38926437
DOI: 10.1038/s41598-024-64769-z -
Journal of Microbiology, Immunology,... Dec 2021Although Streptococcus gallolyticus subspecies pasteurianus (SGSP) is a rare pathogen in children, it can cause invasive infections among neonates and infants. Herein,...
BACKGROUND/PURPOSE
Although Streptococcus gallolyticus subspecies pasteurianus (SGSP) is a rare pathogen in children, it can cause invasive infections among neonates and infants. Herein, we report bacteremia/meningitis caused by SGSP in three neonates and review the literature on bacteremia and/or meningitis caused by this organism.
METHODS
Three neonates, referred from an obstetrics clinic within a 2-month period, presented with invasive SGSP infections. The bacterial isolates were analyzed using Bruker Biotyper MALDI-TOF, sequencing of 16S rRNA and sodA genes (encoding manganese dependent superoxide dismutase), and PCR restriction fragment length polymorphism assay of groESL gene. Molecular typing was performed to evaluate the genetic relatedness.
RESULTS
The median onset age of infection in the three neonates was 3 days (range 2-5 days). They were delivered through cesarean section in the same operation room under different doctors, and were cared for by different nurses. Patient A presented with bacteremia, patient B with bacteremia and meningitis, and patient C with meningitis. Four isolates were identified as SGSP and were susceptible to penicillin G, cefotaxime, and vancomycin. All patients were treated with ampicillin plus cefotaxime for 14 days, and no complications were observed. The molecular typing results suggested that all isolates belonged to a single clone, which indicated the possibility of an outbreak in the obstetrics clinic.
CONCLUSION
Infection by a rare pathogen such as SGSP in multiple patients belonging to a single healthcare unit indicates that detailed investigation and stringent infection control policy are necessary for preventing further outbreaks of such diseases.
Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Cluster Analysis; Cross Infection; Female; Humans; Infant, Newborn; Male; Meningitis; Microbial Sensitivity Tests; RNA, Ribosomal, 16S; Streptococcal Infections; Streptococcus
PubMed: 32768337
DOI: 10.1016/j.jmii.2020.07.004 -
MBio Jan 2021subsp. is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly. Invasive infections by subsp. are strongly linked to the...
subsp. is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly. Invasive infections by subsp. are strongly linked to the occurrence of colorectal cancer (CRC). It was previously shown that increased secondary bile salts under CRC conditions enhance the bactericidal activity of gallocin, a bacteriocin produced by subsp. , enabling it to colonize the mouse colon by outcompeting resident enterococci (L. Aymeric, F. Donnadieu, C. Mulet, L. du Merle, et al., Proc Natl Acad Sci U S A 115:E283-E291, 2018, https://doi.org/10.1073/pnas.1715112115). In a separate study, we showed that subsp. produces and secretes a 21-mer peptide that activates bacteriocin production (A. Proutière, L. du Merle, B. Périchon, H. Varet, et al., mBio 11:e03187-20, 2020, https://doi.org/10.1128/mBio.03187-20). This peptide was named CSP because of its sequence similarity with competence-stimulating peptides found in other streptococci. Here, we demonstrate that CSP is a bona fide quorum sensing peptide involved in activation of gallocin gene transcription. We therefore refer to CSP as GSP (gallocin-stimulating peptide). GSP displays some unique features, since its N-terminal amino acid lies three residues after the double glycine leader sequence. Here, we set out to investigate the processing and export pathway that leads to mature GSP. Heterologous expression in of the genes encoding GSP and the BlpAB transporter is sufficient to produce the 21-mer form of GSP in the supernatant, indicating that subsp. BlpAB displays an atypical cleavage site. We also conducted the first comprehensive structure-activity relationship (SAR) analysis of subsp. GSP to identify its key structural features and found that unlike many other similar streptococci signaling peptides (such as CSPs), nearly half of the mature GSP sequence can be removed (residues 1 to 9) without significantly impacting the peptide activity. subsp. is an opportunistic pathogen associated with colorectal cancer (CRC) and endocarditis. subsp. utilizes quorum sensing (QS) to regulate the production of a bacteriocin (gallocin) and gain a selective advantage in colonizing the colon. In this article, we report (i) the first structure-activity relationship study of the subsp. QS pheromone that regulates gallocin production, (ii) evidence that the active QS pheromone is processed to its mature form by a unique ABC transporter and not processed by an extracellular protease, and (iii) supporting evidence of interspecies interactions between streptococcal pheromones. Our results revealed the minimal pheromone scaffold needed for gallocin activation and uncovered unique interactions between two streptococcal QS signals that warrant further study.
Topics: ATP-Binding Cassette Transporters; Bacterial Proteins; Bacteriocins; Bodily Secretions; Gene Expression Regulation, Bacterial; Membrane Transport Proteins; Peptide Hydrolases; Peptides; Pheromones; Quorum Sensing; Signal Transduction; Streptococcus gallolyticus; Transcriptome
PubMed: 33402540
DOI: 10.1128/mBio.03189-20