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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 -
Poultry Science Oct 2023Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between...
Isolation, characterization, and experimental infection of Streptococcus gallolyticus subspecies pasteurianus from commercial turkeys with acute septicemia: a pilot study.
Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between 1 and 3 wk of age. SG is associated with septicemia resulting in acute mortality with no premonitory signs in turkeys. Three SG isolates were obtained from clinical field cases of acute septicemia of commercial turkeys and used in three independent experiments. In Experiment 1, embryos were inoculated 25 d of embryogenesis with varying concentrations of SG1, SG2, or SG3. In Experiment 2, day of hatch, poults were inoculated with varying concentrations using different routes of administration of SG1, SG2, or SG3. In Experiment 3, day of hatch, poults were inoculated with only isolate SG1 using different paths. Poults were randomly selected for necropsy on d 8 and d 15 and sampled to collect spleen, heart, and liver for SG on d 21, the remaining poults were necropsied and cultured. Samples were plated on Columbia nalidixic acid and colistin agar (CNA) (40°C, 18-24 h). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed suspect colonies. Data were analyzed using the chi-square test of independence, testing all possible combinations to determine significance (P < 0.05). Weight data were subjected to ANOVA using JMP with significance (P < 0.05). No differences were found in BW or BWG on d 0, 8, 15, or 22. Splenomegaly, focal heart necrosis, and pericarditis were observed in all groups in experiments 1 through 3. In Experiment 3, only airsacculitis was observed in a negative control in separate isolation (P > 0.05). On d 21 of Experiment 3, increased (P < 0.05) recovery of SG from spleens were observed in co-housed negative controls, as well as poults challenged by oral gavage (P > 0.05 for d 7 and d 14). These results confirm numerous previous studies indicating that SG subsp. pasteurianus is a primary infectious microorganism that causes septicemia in young poults.
Topics: Animals; Chickens; Pilot Projects; Poultry Diseases; Sepsis; Streptococcus gallolyticus; Turkeys
PubMed: 37540949
DOI: 10.1016/j.psj.2023.102950 -
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 -
Journal of Microbiology, Immunology,... Jun 2023Streptococcus gallolyticus subsp. pasteurianus (SGSP) is a commensal in the intestinal tract and a potential pathogen of neonatal sepsis. During an 11-month period, four...
BACKGROUND
Streptococcus gallolyticus subsp. pasteurianus (SGSP) is a commensal in the intestinal tract and a potential pathogen of neonatal sepsis. During an 11-month period, four consecutive cases of SGSP sepsis were identified in one postnatal care unit (unit A) without evidence of vertical transmission. Therefore, we initiated this study to investigate the reservoir and mode of transmission of SGSP.
METHOD
We performed cultures of stool samples from healthcare workers in unit A and unit B (another unit without SGSP sepsis). If SGSP was positive in feces, we performed isolate pulsotyping and genotyping by using pulsed-field gel electrophoresis (PFGE) and analyzing random amplified polymorphic DNA (RAPD) patterns, respectively.
RESULTS
Five staff members in unit A showed positivity for SGSP. All samples from unit B were negative. We identified two major pulsogroups (groups C and D) by PFGE. In group D, the strains isolated from 3 consecutive sepsis patients (P1, P2 and P3) were closely related and clustered together as those from 2 staff members (C1/C2, C6). One staff (staff 4) had a direct contact history with patient (P1) confirmed to have the same clone. The last isolate of the patient in our study (P4) belonged to a distinct clone.
CONCLUSION
We found prolonged gut colonization of SGSP in healthcare workers and its epidemiological relatedness to neonatal sepsis. Fecal-oral or contact transmission is a possible route of SGSP infection. Fecal shedding among staff may be associated with neonatal sepsis in healthcare facilities.
Topics: Infant, Newborn; Humans; Streptococcus gallolyticus; Neonatal Sepsis; Streptococcal Infections; Random Amplified Polymorphic DNA Technique; Sepsis
PubMed: 36870812
DOI: 10.1016/j.jmii.2023.02.004 -
The Medical Journal of Malaysia May 2023World Health Organization (2019) has declared colorectal cancer (CRC) as the second most common cancer in females and third in males, where the incidence seems to rise...
INTRODUCTION
World Health Organization (2019) has declared colorectal cancer (CRC) as the second most common cancer in females and third in males, where the incidence seems to rise year by year. One of the very few potential pathogens specifically associated with malignant colonic diseases is Streptococcus gallolyticus (Sg). Sg is a part of the intestinal flora which formerly known as biotype I of Streptococcus bovis, belongs to Group D streptococci. Owing to only a few researches done in determining evidence to support Sg as a determinant of CRC, a systematic review is constructed.
MATERIALS AND METHODS
Full-text articles on case-control and cohort studies published from 1st January 2010 to 1st October 2020 were searched using Google Scholar, PubMed and JSTOR. People of all age groups and Sg bacteraemia or colonisation were the type of participant and exposure used for the search strategy, respectively. Data collection was done by three reviewers and checked by two reviewers for discrepancies. All the papers were critically appraised using the STROBE statement. Qualitative synthesis was done by descriptive comparison, distribution of Sg according to stage comparison, method used for Sg detection comparison and risk of bias comparison.
RESULT
Seven out of 11 articles that fulfil the eligibility criteria were selected. Four papers have low overall risk of bias due to low confounding or selection bias. Sg is found to be a risk factor for CRC from three papers studied, whereas the other four papers did not include the strength of association. Only two papers studied the association between the distribution of Sg and stages of CRC, where the results were contradictory from each other, making it to be inconclusive. The most common method used for Sg detection is a culturing technique, followed by molecular and biochemical techniques.
CONCLUSION
There is insufficient evidence to prove the association between Sg bacteraemia as the risk factor for CRC as well as the association between the Sg distribution and stages of CRC. Culturing technique is the most common method used for the detection of bacteria, but it requires subsequent investigations to confirm the presence of Sg. Thus, it is recommended that more studies need to be done using strong statistical analysis to control for most of the confounders with comprehensive explanation and use of more methods in the detection of Sg.
Topics: Male; Female; Humans; Streptococcus gallolyticus; Colorectal Neoplasms; Bacteremia
PubMed: 37271851
DOI: No ID Found -
Indian Journal of Critical Care... Oct 2020is an important cause of bacteremia and infective endocarditis in adults. Studies from other parts of the world have shown a strong association between bacteremia and...
INTRODUCTION
is an important cause of bacteremia and infective endocarditis in adults. Studies from other parts of the world have shown a strong association between bacteremia and colonic neoplasia. The profile of bacteremia is understudied in Indian population.
MATERIALS AND METHODS
We retrospectively analyzed the data of 16 patients with bacteremia obtained from microbiology registry. BacT/ALERT positive samples were inoculated into blood agar, chocolate agar, and MacConkey agar. Organisms were identified by the VITEK 2 microbial identification system, and susceptibility was done by the microbroth dilution method as per Clinical and Laboratory Standards Institute (CLSI) M100 guidelines. Clinical details were obtained from electronic medical records.
RESULTS
Majority of our isolates were subspecies . Total 16 patients had isolated from blood over a 1 year period. The median age was 58 years (IQR: 46.5-66). Eleven were males; type II diabetes mellitus and chronic liver disease were the common comorbidities observed in our patients. None of our patients had underlying infective endocarditis or colonic malignancy. Penicillin sensitivity was 81.2% while all the isolates were susceptible to ceftriaxone. Ampicillin resistance was seen in only one of the isolates. In-hospital mortality was 12.5%.
CONCLUSION
subsp. is the commonest subspecies of isolated in our population. Unlike previous studies, colonic neoplasia and infective endocarditis were rare in our patients. Type II diabetes mellitus and chronic liver disease were the commonest risk factors identified in patients with bacteremia.
HOW TO CITE THIS ARTICLE
Niyas VKM, Arjun R, Sasidharan A, Palakunnath GA. Bacteremia: An Experience from a Tertiary Center in South India. Indian J Crit Care Med 2020;24(10):943-945.
PubMed: 33281319
DOI: 10.5005/jp-journals-10071-23569 -
Infection and Drug Resistance 2020, formerly known as one of the group, is frequently associated with endocarditis. Current guidelines recommended diagnostic work-up for endocarditis among patients with...
BACKGROUND
, formerly known as one of the group, is frequently associated with endocarditis. Current guidelines recommended diagnostic work-up for endocarditis among patients with bacteremia. However, subsp. , was found to be associated with neonatal sepsis and liver diseases and is less commonly associated with endocarditis compared with subsp. . Our study aimed to identify the risk factors for subsp. endocarditis to help select the patients for echocardiography.
METHODS
In this retrospective cohort study, medical records from all adult patients with subsp. isolated from blood cultures at Phramongkutklao Hospital from 2009 to 2015 were reviewed. Patients who had mixed bacteremia or missing records were excluded from the study.
RESULTS
During the study period, subsp. was isolated among 106 individuals. Mean age was 66.9±15.6 years. Most patients (61.3%) were male, with cirrhosis as the most common underlying diseases (46.2%), followed by malignancy and chronic kidney disease. Most common manifestations included primary bacteremia (44.3%), followed by spontaneous bacterial peritonitis (23.6%). Infective endocarditis was found among 9 patients. No patients with cirrhosis or single blood specimen of bacteremia had endocarditis (RR 0; p-value 0.003, and RR 1.35; p-value 0.079). The common complications associated with endocarditis were acute respiratory failure (RR 4.32; p-value 0.05), whereas acute kidney injury was a protective factor (RR 0; p-value 0.01). Among 76 patients who had records of 2-year follow-up, no new diagnosis of endocarditis or malignancy was observed.
CONCLUSION
Among patients with subsp. bacteremia, echocardiography might not be needed among patients with cirrhosis and without sustained bacteremia.
PubMed: 32765016
DOI: 10.2147/IDR.S265722 -
Infection and Drug Resistance 2023subspecies , formerly classified as biotype II/2 until 2003, is a rare cause of infant meningitis. Over the past 2 decades, only a few individual case reports and...
subspecies , formerly classified as biotype II/2 until 2003, is a rare cause of infant meningitis. Over the past 2 decades, only a few individual case reports and limited case series exist in the English-language literature. Moreover, the pathogenesis of subsp. meningitis in infants is unclear. Here we report a case of meningitis in a 6-week-old infant with hypothyroidism and preceding diarrhea. In this case, was cultured from cerebrospinal fluid, and then subspecies was identified by metagenomic next-generation Sequencing. The infant recovered uneventfully after a 4-week antibiotic course with ceftriaxone and vancomycin. Then combined with the literature of subsp. meningitis in infants, we discuss the possible etiology.
PubMed: 37727275
DOI: 10.2147/IDR.S425637 -
Frontiers in Cellular and Infection... 2021The opportunistic pathogen is one of the few intestinal bacteria that has been consistently linked to colorectal cancer (CRC). This study aimed to identify novel...
OBJECTIVE
The opportunistic pathogen is one of the few intestinal bacteria that has been consistently linked to colorectal cancer (CRC). This study aimed to identify novel -induced pathways in colon epithelial cells that could further explain how contributes to CRC development.
DESIGN AND RESULTS
Transcription profiling of cultured CRC cells that were exposed to revealed the specific induction of oxidoreductase pathways. Most prominently, and genes that encode phase I biotransformation enzymes were responsible for the detoxification or bio-activation of toxic compounds. A common feature is that these enzymes are induced through the Aryl hydrocarbon receptor (AhR). Using the specific inhibitor CH223191, we showed that the induction of was dependent on the AhR both using multiple CRC cell lines as using wild-type C57bl6 mice colonized with . Furthermore, we showed that CYP1 could also be induced by other intestinal bacteria and that a yet unidentified diffusible factor from the secretome (SGS) induces CYP1A enzyme activity in an AhR-dependent manner. Importantly, priming CRC cells with SGS increased the DNA damaging effect of the polycyclic aromatic hydrocarbon 3-methylcholanthrene.
CONCLUSION
This study shows that gut bacteria have the potential to modulate the expression of biotransformation pathways in colonic epithelial cells in an AhR-dependent manner. This offers a novel theory on the contribution of intestinal bacteria to the etiology of CRC by modifying the capacity of intestinal epithelial or (pre-)cancerous cells to (de)toxify dietary components, which could alter intestinal susceptibility to DNA damaging events.
Topics: Animals; Biotransformation; Colorectal Neoplasms; Cytochrome P-450 CYP1A1; Epithelial Cells; Mice; Mice, Inbred C57BL; Receptors, Aryl Hydrocarbon; Streptococcus gallolyticus
PubMed: 34778104
DOI: 10.3389/fcimb.2021.740704