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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 -
Microbiology Spectrum Mar 2019Streptococci carrying serogroup C and G antigens, and in particular, subsp. (SDSE), are emerging human pathogens that are increasingly isolated from patients with a... (Review)
Review
Streptococci carrying serogroup C and G antigens, and in particular, subsp. (SDSE), are emerging human pathogens that are increasingly isolated from patients with a myriad of infections that range from mundane to life-threatening. SDSE is microbiologically similar to . These streptococci frequently cause infections of the throat and skin and soft tissues. Moreover, they may invade the bloodstream and disseminate widely to many deep tissue sites, including the endocardium. Life-threatening invasive infections due to SDSE, including the streptococcal toxic shock syndrome, occur most frequently in patients with severe underlying medical diseases. Treatment with penicillin is adequate under most circumstances, but treatment failure occurs. SDSE may also be resistant to other antibiotic classes including tetracyclines, macrolides, and clindamycin. Most human infections caused by groups C and G streptococci are transmitted from person to person, but infections due to subsp. (and, rarely, to subsp. ) are zoonoses. Transmission of these latter species occurs by animal contact or by contamination of food products and has been associated with the development of poststreptococcal glomerulonephritis. Members of the group, usually classified with the viridans group of streptococci, are associated with a variety of pyogenic infections.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Glomerulonephritis; Humans; Pharyngitis; Streptococcal Infections; Streptococcus; Zoonoses
PubMed: 30977463
DOI: 10.1128/microbiolspec.GPP3-0016-2018 -
Gut Jun 2018We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis.
OBJECTIVES
We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis.
DESIGN
We performed 16S rRNA gene analysis of gastric mucosal samples from 81 cases including superficial gastritis (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC) from Xi'an, China, to determine mucosal microbiome dysbiosis across stages of GC. We validated the results in mucosal samples of 126 cases from Inner Mongolia, China.
RESULTS
We observed significant mucosa microbial dysbiosis in IM and GC subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in GC compared with SG (q<0.05). Microbial network analysis showed increasing correlation strengths among them with disease progression (p<0.001). Five GC-enriched bacterial taxa whose species identifications correspond to , , , and had significant centralities in the GC ecological network (p<0.05) and classified GC from SG with an area under the receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among gastric microbes were observed in -negative samples compared with -positive samples in SG and IM. The fold changes of selected bacteria, and strengths of their interactions were successfully validated in the Inner Mongolian cohort, in which the five bacterial markers distinguished GC from SG with an AUC of 0.81.
CONCLUSIONS
In addition to microbial compositional changes, we identified differences in bacterial interactions across stages of gastric carcinogenesis. The significant enrichments and network centralities suggest potentially important roles of , , , and in GC progression.
Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Carcinogenesis; Cell Transformation, Neoplastic; China; Dysbiosis; Female; Gastric Mucosa; Humans; Male; Microbiota; Middle Aged; RNA, Ribosomal, 16S; Stomach; Stomach Neoplasms; Young Adult
PubMed: 28765474
DOI: 10.1136/gutjnl-2017-314281 -
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 -
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 -
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 -
Infection and Immunity May 2023For many years, Streptococcus anginosus has been considered a commensal colonizing the oral cavity, as well as the gastrointestinal and genitourinary tracts. However,...
For many years, Streptococcus anginosus has been considered a commensal colonizing the oral cavity, as well as the gastrointestinal and genitourinary tracts. However, recent epidemiological and clinical data designate this bacterium as an emerging opportunistic pathogen. Despite the reported pathogenicity of S. anginosus, the molecular mechanism underpinning its virulence is poorly described. Therefore, our goal was to develop and optimize efficient and simple infection models that can be applied to examine the virulence of S. anginosus and to study host-pathogen interactions. Using 23 S. anginosus isolates collected from different infections, including severe and superficial infections, as well as an attenuated strain devoid of CppA, we demonstrate for the first time that Dictyostelium discoideum is a suitable model for initial, fast, and large-scale screening of virulence. Furthermore, we found that another nonvertebrate animal model, Galleria mellonella, can be used to study the pathogenesis of S. anginosus infection, with an emphasis on the interactions between the pathogen and host innate immunity. Examining the profile of immune defense genes, including antimicrobial peptides, opsonins, regulators of nodulation, and inhibitors of proteases, by quantitative PCR (qPCR) we identified different immune response profiles depending on the S. anginosus strain. Using these models, we show that S. anginosus is resistant to the bactericidal activity of phagocytes, a phenomenon confirmed using human neutrophils. Notably, since we found that the data from these models corresponded to the clinical severity of infection, we propose their further application to studies of the virulence of S. anginosus.
Topics: Animals; Humans; Virulence; Dictyostelium; Streptococcus anginosus; Moths; Virulence Factors; Disease Models, Animal; Larva
PubMed: 37097148
DOI: 10.1128/iai.00016-23