-
Cell Feb 2024Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse...
Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
Topics: Animals; Humans; Mice; Atrophy; Carcinogenesis; Cell Transformation, Neoplastic; Gastric Mucosa; Gastritis; Inflammation; Mitogen-Activated Protein Kinases; Stomach Neoplasms; Streptococcus anginosus; Streptococcal Infections
PubMed: 38295787
DOI: 10.1016/j.cell.2024.01.004 -
Frontiers in Microbiology 2022Three distinct streptococcal species: , and , belonging to the group (SAG), also known as group, have been attracting clinicians and microbiologists, not only as oral... (Review)
Review
Three distinct streptococcal species: , and , belonging to the group (SAG), also known as group, have been attracting clinicians and microbiologists, not only as oral commensals but also as opportunistic pathogens. For years they have been simply classified as so called viridans streptococci, and distinct species were not associated with particular clinical manifestations. Therefore, description of SAG members are clearly underrepresented in the literature, compared to other medically relevant streptococci. However, the increasing number of reports of life-threatening infections caused by SAG indicates their emerging pathogenicity. The improved clinical data generated with the application of modern molecular diagnostic techniques allow for precise identification of individual species belonging to SAG. This review summarizes clinical reports on SAG infections and systematizes data on the occurrence of individual species at the site of infection. We also discuss the issue of proper microbiological diagnostics, which is crucial for further clinical treatment.
PubMed: 35898914
DOI: 10.3389/fmicb.2022.956677 -
Gut Sep 2020is associated with gastric inflammation, precancerous gastric atrophy (GA) and intestinal metaplasia (IM). We aimed to identify microbes that are associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
is associated with gastric inflammation, precancerous gastric atrophy (GA) and intestinal metaplasia (IM). We aimed to identify microbes that are associated with progressive inflammation, GA and IM 1 year after eradication.
DESIGN
A total of 587 -positive patients were randomised to receive eradication therapy (295 patients) or placebo (292 patients). Bacterial taxonomy was analysed on 404 gastric biopsy samples comprising 102 pairs before and after 1 year eradication and 100 pairs before and after 1 year placebo by 16S rRNA sequencing.
RESULTS
Analysis of microbial sequences confirmed the eradication of in treated group after 1 year. Principal component analysis revealed distinct microbial clusters reflected by increase in bacterial diversity (p<0.00001) after eradication. While microbial interactions remained largely unchanged after placebo treatment, microbial co-occurrence was less in treated group. , and were enriched while and were depleted in patients with persistent inflammation 1 year after eradication. A distinct cluster of oral bacteria comprising , , , and were associated with emergence and persistence of GA and IM. Probiotic was depleted in subjects who developed GA following eradication. Functional pathways including amino acid metabolism and inositol phosphate metabolism were enriched while folate biosynthesis and NOD-like receptor signalling decreased in atrophy/IM-associated gastric microbiota.
CONCLUSION
This study identified that gastric microbes contribute to the progression of gastric carcinogenesis after eradication.
Topics: Bacteria; Biopsy; Carcinogenesis; Disease Eradication; Disease Progression; Female; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Microbial Interactions; Middle Aged; Sequence Analysis, RNA; Stomach
PubMed: 31974133
DOI: 10.1136/gutjnl-2019-319826 -
American Journal of Obstetrics and... Aug 2019Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such...
Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.
BACKGROUND
Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome.
OBJECTIVE
To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation.
STUDY DESIGN
The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation.
RESULTS
Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases.
CONCLUSION
In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.
Topics: Adult; Amniocentesis; Amniotic Fluid; Anti-Bacterial Agents; Biomarkers; Candida albicans; Ceftriaxone; Cerclage, Cervical; Chorioamnionitis; Clarithromycin; Delivery, Obstetric; Female; Humans; Interleukin-6; Leukocytes; Matrix Metalloproteinase 8; Metronidazole; Pregnancy; Retrospective Studies; Streptococcus anginosus; Ureaplasma; Uterine Cervical Incompetence
PubMed: 30928565
DOI: 10.1016/j.ajog.2019.03.017 -
Circulation Aug 2023Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify...
BACKGROUND
Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.
METHODS
We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.
RESULTS
The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for and subsp (<1×10). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.
CONCLUSIONS
This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
Topics: Humans; Female; Middle Aged; Male; Coronary Artery Disease; Cross-Sectional Studies; Calcium; Atherosclerosis; Streptococcus
PubMed: 37435755
DOI: 10.1161/CIRCULATIONAHA.123.063914 -
Frontiers in Microbiology 2022together with and constitute the group (SAG), until recently considered to be benign commensals of the human mucosa isolated predominantly from oral cavity, but also... (Review)
Review
together with and constitute the group (SAG), until recently considered to be benign commensals of the human mucosa isolated predominantly from oral cavity, but also from upper respiratory, intestinal, and urogenital tracts. For years the virulence potential of SAG was underestimated, mainly due to complications in correct species identification and their assignment to the physiological microbiota. Still, SAG representatives have been associated with purulent infections at oral and non-oral sites resulting in abscesses formation and empyema. Also, life threatening blood infections caused by SAG have been reported. However, the understanding of SAG as potential pathogen is only fragmentary, albeit certain aspects of SAG infection seem sufficiently well described to deserve a systematic overview. In this review we summarize the current state of knowledge of the pathogenicity factors and their mechanisms of action.
PubMed: 36386673
DOI: 10.3389/fmicb.2022.1025136 -
Frontiers in Microbiology 2022Two-component signal transduction (TCS) systems are important regulatory pathways in streptococci. A typical TCS encodes a membrane-anchored sensor kinase (SK) and a... (Review)
Review
Two-component signal transduction (TCS) systems are important regulatory pathways in streptococci. A typical TCS encodes a membrane-anchored sensor kinase (SK) and a cytoplasmic response regulator (RR). Approximately, 20 different types of TCSs are encoded by various streptococci. Among them, two TCSs, in particular BlpRH and ComDE, are required for bacteriocins production and competence development. The SK component of these two TCSs is highly similar and belongs to the protein kinase-10 (HPK-10) subfamily. While these two TCSs are present in streptococci, no systematic studies have been done to differentiate between these two TCSs, and the existence of these pathways in several species of the genus Streptococcus is also unknown. The lack of information about these pathways misguided researchers for decades into believing that the BlpRH system is a ComDE system. Here, we have attempted to distinguish between the BlpRH and ComDE systems based on the location of the chromosome, genomic arrangement, and conserved residues. Using the SyntTax and NCBI databases, we investigated the presence of both TCS systems in the genome of several streptococcal species. We noticed that the NCBI database did not have proper annotations for these pathways in several species, and many of them were wrongly annotated, such as CitS or DpiB instead of BlpH. Nevertheless, our critical analyses led us to classify streptococci into two groups: class A (only the BlpRH system) and class B (both the BlpRH and ComDE systems). Most of the streptococcal groups, including bovis, pyogenic, mutans, salivarius, and suis, encode only the BlpRH system. In contrast, only in the mitis and anginosus groups were both the TCS systems present. The focus of this review is to identify and differentiate between the BlpRH and ComDE systems, and discuss these two pathways in various streptococci.
PubMed: 36353461
DOI: 10.3389/fmicb.2022.960994 -
IDCases 2020Vascular graft infections are rare complications, usually associated with a monomicrobial pyogenic culture. We report a case of vascular graft co-infection with and ,...
Vascular graft infections are rare complications, usually associated with a monomicrobial pyogenic culture. We report a case of vascular graft co-infection with and , complicated by an aorto-duodenal fistula. Screening for chronic co-infection in at-risk patients might prevent adverse long-term outcomes.
PubMed: 32021800
DOI: 10.1016/j.idcr.2020.e00697 -
Journal of Infection and Public Health Nov 2020Data on patients with invasive Streptococcus anginosus group (SAG) infections is limited, as it's been considered commensal bacteria in the human microbiota. We...
BACKGROUND
Data on patients with invasive Streptococcus anginosus group (SAG) infections is limited, as it's been considered commensal bacteria in the human microbiota. We conducted an analysis of SAG infections to assist clinicians in understanding their burden and clinical outcomes.
METHODS
A retrospective study of medical records, identifying invasive SAG bacteria of sterile-site isolates that were managed from May 2015 to April 2017, at a tertiary care hospital in Riyadh, Saudi Arabia. Demographic data, clinical presentation, site of infection, antibiotic use, and outcome were recorded and analyzed to identify factors associated with poor outcome and/or polymicrobial growth.
RESULTS
We identified 105 cases of SAG infections in adults, with 52% of the patients being male and the mean age of 52.4 years with comorbidities occurring in more than half of the cases such as diabetes (38%) and malignancy (15%). Overall mortality was 6%, and it was statistically associated with age older than 65 years, polymicrobial growth and a history of malignancy. The infection frequencies were skin and soft tissue infections (SSTI; 55%), intra-abdominal infections (24%), bacteremia (14%), genitourinary infections (8.5%), and pleuropulmonary infections (5%). Abscesses accounted for 68% of cases. Polymicrobial infection (46%) with Enterobacteriaceae and Gram-negative anaerobes coincided with SAG infection. Polymicrobial growth was significantly associated with abscess formation, intra-abdominal source of infections, and poor outcome. In addition, death in patients with SAG was statistically associated with patients older than 65 years of age and those with history of cancer or transplant.
CONCLUSION
SSTIs and intra-abdominal infections are the most common clinical presentations in our cohort. Bacteremia was uncommon; however, the prognosis is less favorable. Overall susceptibility to penicillin was 91%, therefore β-lactam antibiotics are the drug of choice and additional coverage for anaerobic and gram-negative bacteria should be considered for intra-abdominal collection and solid or organ abscesses.
Topics: Adult; Aged; Anti-Bacterial Agents; Female; Humans; Male; Middle Aged; Retrospective Studies; Saudi Arabia; Streptococcal Infections; Streptococcus anginosus; Tertiary Care Centers
PubMed: 32917555
DOI: 10.1016/j.jiph.2020.07.017