Co-culturing with Streptococcus anginosus alters Staphylococcus aureus transcriptome when exposed to tonsillar cells.

Introduction: Improved understanding of Staphylococcus aureus throat colonization in the presence of other co-existing microbes is important for mapping S. aureus adaptation to the human throat, and recurrence of infection. Here, we explore the responses triggered by the encounter between two common throat bacteria, S. aureus and Streptococcus anginosus, to identify genes in S. aureus that are important for colonization in the presence of human tonsillar epithelial cells and S. anginosus, and further compare this transcriptome with the genes expressed in S. aureus as only bacterium. Methods: We performed an in vitro co-culture experiment followed by RNA sequencing to identify interaction-induced transcriptional alterations and differentially expressed genes (DEGs), followed by gene enrichment analysis. Results and discussion: A total of 332 and 279 significantly differentially expressed genes with p-value < 0.05 and log2 FoldChange (log2FC) ≥ |2| were identified in S. aureus after 1 h and 3 h co-culturing, respectively. Alterations in expression of various S. aureus survival factors were observed when co-cultured with S. anginosus and tonsillar cells. The serine-aspartate repeat-containing protein D (sdrD) involved in adhesion, was for example highly upregulated in S. aureus during co-culturing with S. anginosus compared to S. aureus grown in the absence of S. anginosus, especially at 3 h. Several virulence genes encoding secreted proteins were also highly upregulated only when S. aureus was co-cultured with S. anginosus and tonsillar cells, and iron does not appear to be a limiting factor in this environment. These findings may be useful for the development of interventions against S. aureus throat colonization and could be further investigated to decipher the roles of the identified genes in the host immune response in context of a throat commensal landscape.

Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice.

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.

Oral streptococci S. anginosus and S. mitis induce distinct morphological, inflammatory, and metabolic signatures in macrophages.

Oral streptococci, key players in oral biofilm formation, are implicated in oral dysbiosis and various clinical conditions, including dental caries, gingivitis, periodontal disease, and oral cancer. Specifically, Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers, while Streptococcus mitis is linked to oral cancer. However, no study has investigated the mechanistic links between these Streptococcus species and cancer-related inflammatory responses. As an initial step, we probed the innate immune response triggered by S. anginosus and S. mitis in RAW264.7 macrophages. These bacteria exerted time- and dose-dependent effects on macrophage morphology without affecting cell viability. Compared with untreated macrophages, macrophages infected with S. anginosus exhibited a robust proinflammatory response characterized by significantly increased levels of inflammatory cytokines and mediators, including TNF, IL-6, IL-1ß, NOS2, and COX2, accompanied by enhanced NF-κB activation. In contrast, S. mitis-infected macrophages failed to elicit a robust inflammatory response. Seahorse Xfe96 analysis revealed an increased extracellular acidification rate in macrophages infected with S. anginosus compared with S. mitis. At the 24-h time point, the presence of S. anginosus led to reduced extracellular itaconate, while S. mitis triggered increased itaconate levels, highlighting distinct metabolic profiles in macrophages during infection in contrast to aconitate decarboxylase expression observed at the 6-h time point. This initial investigation highlights how S. anginosus and S. mitis, two Gram-positive bacteria from the same genus, can prompt distinct immune responses and metabolic shifts in macrophages during infection.IMPORTANCEThe surge in head and neck cancer cases among individuals devoid of typical risk factors such as Human Papilloma Virus (HPV) infection and tobacco and alcohol use sparks an argumentative discussion around the emerging role of oral microbiota as a novel risk factor in oral squamous cell carcinoma (OSCC). While substantial research has dissected the gut microbiome's influence on physiology, the oral microbiome, notably oral streptococci, has been underappreciated during mucosal immunopathogenesis. Streptococcus anginosus, a viridans streptococci group, has been linked to abscess formation and an elevated presence in esophageal cancer and OSCC. The current study aims to probe the innate immune response to S. anginosus compared with the early colonizer Streptococcus mitis as an important first step toward understanding the impact of distinct oral Streptococcus species on the host immune response, which is an understudied determinant of OSCC development and progression.

ENDOGENOUS ENDOPHTHALMITIS DUE TO STREPTOCOCCUS ANGINOSUS IN A HEALTHY, YOUNG WOMAN.

PURPOSE: The purpose of this study was to present a case of indolent endogenous endophthalmitis in a young, seemingly healthy woman. METHODS: This study is a retrospective case report. RESULTS: A 25-year-old woman with no significant medical history presented with vision loss in the left eye over the course of 1 month. Examination showed vitritis and a white-yellow lesion overlying the macula and optic nerve in the left eye. Initial laboratory testing for infectious and inflammatory causes was unrevealing. A diagnostic vitrectomy was performed, and the patient was found to have presumed endogenous endophthalmitis due to Streptococcus anginosus, an extremely uncommon bacterium. Subsequent workup did not reveal evidence of bacteremia, endocarditis, or orbital infection. This case is unique because, unlike the three previously reported cases of S. anginosus endophthalmitis, this patient was seemingly healthy, never had an elevated white blood cell count, never had documented bacteremia, had a normal echocardiogram, and had normal orbital findings on magnetic resonance imaging and computed tomography scans. Further questioning revealed a remote history of facial cellulitis and possible sinusitis treated with oral antibiotics, which are the presumed etiology. CONCLUSION: Streptococcus anginosus endophthalmitis can occur in young, seemingly healthy patients. Endogenous endophthalmitis should be considered in the differential diagnosis even without systemic comorbidities or other risk factors. Detailed questioning about medical history and thorough review of systems, including nonocular symptoms, are essential.

Pertinence of Streptococcus anginosus group in intracerebral abscesses in the era of extended antibiotic resistance.

AIMS: • To study the incidence of Streptococcus anginosus group (SAG) in pyogenic or community acquired intra cerebral abscess. • To understand the risk factors for the same. • To analyze the specific radiological features and clinical outcome after surgery and antibiotic therapy. METHODS: This is a retrospective observational study of case series over a period of one year. Patients diagnosed with intracerebral abscess were included in the study. Pus collected from were received in the laboratory and processed according to the standard protocols. Data regarding the clinical findings and demographics were collected from medical records. FINDINGS: A total of 202 samples were studied. 103 were found to be pyogenic. SAG were isolated from 21 samples (20.38%) and all the isolates were sensitive to Penicillin. Age of the patients ranged from 18months to 68years. Male preponderance was noted with male to female ratio of 4:1. Otogenic infections were the most common predisposing factors and focus of infection could not be ascertained in 5 patients. All patients were treated with surgical intervention and antibiotics (Vancomycin, Amikacin and Metronidazole) for 6 weeks and recovery was remarkable. One patient succumbed to the illness. CONCLUSION: SAG can be an aggressive pathogen with propensity for abscess formation. Chronic Suppurative Otitis Media (CSOM) is still a major cause of intracerebral abscess in developing country like India which is a benign and curable disease and should not be neglected. Injudicious use of antibiotics and negligence regarding the dose and duration of therapy from both patients and health care providers is the major cause for common infections to become more difficult to treat and succumbing to complications.

A mixed infection involving Bacteroides denticanum, Lactobacillus salivarius, and Streptococcus anginosus as causative agents of abscess around a pharyngo-esophageal anastomosis and acute vertebral osteomyelitis: Identification by ribosomal RNA sequencing of bacterial isolates.

"Bacteroides denticanum" is an anaerobic, non-spore-forming, gram-negative bacterium with a rod morphology typical of canine, ovine, and macropod oral flora. There is only one report of bloodstream infection caused by "B. denticanum" from a dog bite in human. Here, we report a case with no history of animal contact who developed an abscess caused by "B. denticanum" around a pharyngo-esophageal anastomosis after undergoing balloon dilatation procedure for stenosis following laryngectomy. The patient was a 73-year-old man with laryngeal cancer, esophageal cancer, hyperuricemia, dyslipidemia, and hypertension with a 4-week history of cervical pain, sore throat, and fever. Computed tomography showed fluid collection on the posterior pharyngeal wall. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) identified Bacteroides pyogenes, Lactobacillus salivarius, and Streptococcus anginosus from abscess aspiration. 16S ribosomal RNA sequencing re-identified the Bacteroides species as "B. denticanum". T2-weighted magnetic resonance images showed a high signal intensity adjacent to the anterior vertebral body of C3-C7. The diagnosis was peripharyngeal esophageal anastomotic abscess and acute vertebral osteomyelitis caused by "B. denticanum", L. salivarius, and S. anginosus. The patient was treated with sulbactam ampicillin intravenously for 14 days and then switched to oral amoxicillin with clavulanic acid for 6 weeks. To our knowledge, this is the first report of a human infection caused by "B. denticanum" without a history of animal contact. Despite remarkable advancements facilitated by MALDI-TOF MS in microbiological diagnosis, the accurate identification of novel, emerging, or uncommon microorganisms and comprehending their pathogenicity, suitable therapy, and follow up necessitate sophisticated molecular approaches.

Studies of Streptococcus anginosus Virulence in Dictyostelium discoideum and Galleria mellonella Models.

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.

Comparative Genomic Study of Streptococcus anginosus Reveals Distinct Group of Urinary Strains.

Streptococcus anginosus is a prevalent member of the human flora. While it has been found in the microbiota of "healthy" asymptomatic individuals, it has also been associated with genitourinary tract infections and bacteremia. Based upon multilocus sequence analysis, two subspecies and two genomosubspecies have been characterized for the species. We previously conducted whole-genome sequencing of 85 S. anginosus isolates from the urinary tract. Here, we present genomic analysis of this species, including isolates from the urinary tract as well as gut and fecal, vaginal, oral, respiratory, and blood and heart samples. Average nucleotide identity and core genome analysis revealed that these strains form two distinct groups. Group 1 is comprised of the S. anginosus type strain and other previously identified S. anginosus subspecies and genomosubspecies, including isolates from throughout the human body. In contrast, group 2 consists of predominantly urinary streptococci (n = 77; 85.6%). Both of these S. anginosus groups are distinct from other members of the Streptococcus anginosus group (SAG) species S. intermedius and S. constellatus. Genes conserved among all strains of one group but not in any strains in the other group were next identified. Group 1 strains included genes found in S. intermedius and S. constellatus, suggesting that they were lost within the ancestor of the group 2 strains. In contrast, genes unique to the group 2 strains were homologous to more distant streptococci, indicative of acquisition via horizontal gene transfer. These genes are ideal candidates for use as marker genes to distinguish between the two groups in the human microbiota. IMPORTANCE Whole-genome analysis of S. anginosus strains provides greater insight into the diversity of this species than from marker genes alone. Our investigation of 166 publicly available S. anginosus genomes via average nucleotide identity and core genome analysis revealed two phylogenomically distinct groups of this species, with one group almost exclusively consisting of isolates from the urinary tract. In contrast, only 8 urinary strains were identified within the other group, which contained the S. anginosus type strain, as well as all identified subspecies and genomosubspecies. While genomic analysis suggested that this urinary group of S. anginosus is genomically different from the previously characterized S. anginosus subspecies, phenotypic characterization is still needed. Given prior reports of the prevalence of S. anginosus in the urinary tract of both continent and incontinent females, future studies are needed to investigate if the symptom state of the urinary tract is associated with these two different groups.

A rare paediatric case of possible infective endocarditis caused by Streptococcus anginosus.

Infective endocarditis in children is a rare but serious condition that requires prompt management. We present a case of an 11-year-old boy with subacute bacterial endocarditis caused by Streptococcus anginosus, an unusual causative microorganism for infective endocarditis. The patient presented with a history of malaise, fatigue, and one subjective tactile fever. To the best of our knowledge, this is the first paediatric case of possible infective endocarditis caused by Streptococcus anginosus.

Streptococcus anginosus: a stealthy villain in deep odontogenic abscesses.

Odontogenic infections (OIs) occasionally spread to deep facial and neck tissues. Our study aimed to explore the role of Streptococcus anginous group (SAG) in these severe OIs. A retrospective study of patients aged ≥ 18 years who required hospital care for acute OI was conducted. We analysed data of OI microbial samples and recorded findings of SAG and other pathogens. These findings were compared with data regarding patients' prehospital status and variables of infection severity. In total, 290 patients were included in the analyses. The most common (49%) bacterial finding was SAG. Other common findings were Streptococcus viridans and Prevotella species, Parvimonas micra, and Fusobacterium nucleatum. Infection severity variables were strongly associated with SAG occurrence. Treatment in an intensive care unit was significantly more common in patients with SAG than in patients without SAG (p < 0.001). In addition, SAG patients expressed higher levels of C-reactive protein (p = 0.001) and white blood cell counts (p < 0.001), and their hospital stays were longer than those of non-SAG patients (p = 0.001). SAG is a typical finding in severe OIs. Clinical features of SAG-related OIs are more challenging than in other OIs. Early detection of SAG, followed by comprehensive infection care with prompt and careful surgical treatment, is necessary due to the aggressive behaviour of this dangerous pathogen.

Holospinal epidural abscess caused by Streptococcus anginosus group: a literature review.

Spinal epidural abscess (SEA) usually extends over three to four vertebrae. We present a case of holospinal epidural abscess (HEA) caused by the Streptococcus anginosus group (SAG). A man in his 40s with a 2-week history of fever, back pain, and progressive tetraparesis was referred to us from the local hospital. MRI showed epidural fluid collection from C2 to S1. Blood and pus cultures revealed the presence of SAG. He was treated by emergency laminoplasty, epidural drainage and antibiotic treatment. After the 111st hospital day, his manual muscle test was shown to improve; hence, he was transferred for rehabilitation. According to the previous reports, we identified 12 cases of SEA extending from the cervical spine to the sacrum, including our case. For one-fourth of these cases, SAG was the causative organism of this rare SEA. Therefore, SAG should be considered causative organisms in HEA.

Clinical Microbial Identification of Severe Oral Infections by MALDI-TOF Mass Spectrometry in Stockholm County: an 11-Year (2010 to 2020) Epidemiological Investigation.

Growing evidence suggests that oral infections can modify the course of systemic diseases. To date, epidemiological data on microbial oral infections are scarce. Here, we performed a comprehensive analysis of the trend and microbial diversity in oral infection specimens referred for clinical microbiology analysis from 2010 to 2020. The microbes were isolated by culture and were identified via matrix-assisted laser desorption ionization-time of flight mass spectrometry technology (MALDI-TOF MS) throughout the study period. A total of 1,014 referred samples from dental clinics in Stockholm County with dentoalveolar abscesses and jaw osteomyelitis being the main reason were identified. Overall, the microbial composition was dominated by Firmicutes (51%), followed by Bacteroidetes (19%), Proteobacteria (12%), and Actinobacteria (5%). At the genus level, Streptococcus spp. (36%), Prevotella spp. (18%), and Staphylococcus spp. (11%) were among the most frequently reported. Interestingly, a strong increase in trend was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, and Granulicatella adiacens during the study time (R = 0.66 to 0.89, P < 0.05), and a minor increase was noted for Enterococcus faecalis and Klebsiella spp., whereas steady levels were noted for most of the others. The present study shows the diversity of bacteria that have been involved in dental infections during the last decade in the capital of Sweden, as well as the emerging oral microbiota trend, with clear clinical implications on the oral-systemic link. IMPORTANCE Oral diseases and associated microbes are a risk factor for systemic diseases and can change the courses of these diseases. To date, epidemiological data on microbial oral infections are scarce, and longitudinal reports are lacking. We present for the first time the microbial composition of severe oral bacterial infections determined via the MALDI-TOF mass spectrometry technique in a comprehensive study between 2010 and 2020 (11 years) in Stockholm County. The trend and microbial diversity of oral infections were analyzed on referred clinical microbiological samples and were processed by standardized protocols. Trend increase was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, Granulicatella adiacens, Enterococcus faecalis, and Klebsiella spp. Our results provide new insights into the diversity and trend of oral microbiota that were involved in serious oral infections over the past decade in the capital of Sweden and may influence the oral-systemic link.

Laboratory Diagnosis, Antimicrobial Susceptibility And Genuine Clinical Spectrum of Streptococcus anginosus Group; Our Experience At A University Hospital.

Background: Streptococcus anginosus group (SAG) may be unrecognized or misidentified in the Clinical Microbiology Laboratory resulting in under-reporting. Consequently, their role as genuine pathogens remains underestimated. Objectives: The aim of this study is to suggest a reasonable identification approach that is suitable for laboratories of limited resources, to detect any possible emerging antimicrobial resistance, and to assess the genuine clinical spectrum of infections that are caused solely by SAG. Methods: Our research included 190 bacterial isolates from 190 patients. The isolates were examined by colonies' morphology, odor, hemolytic pattern on 5% sheep Blood agar and Gram staining. Lancefield serogrouping was determined by agglutination test. Antimicrobial susceptibility testing (AST) was performed by disc diffusion method. The isolates were subjected to automated identification and AST by Vitek 2 compact instrument. The collected patients' data included age, gender, clinical condition and/or site of infection, and probable predisposing factor. Results: All isolates produced minute-sized colonies that consistently generated distinct odor. The isolates showed variable hemolytic patterns, and the majority (74.7%) were non-hemolytic. The isolates showed different Lancefield serogroups, and the commonest was group F (54.2%). A total of 188 (98.9%) isolates were identified by Vitek 2 compact instrument at ≥95% confidence. The isolates showed high rates of antimicrobial susceptibility, however the highest rate of antimicrobial resistance was detected to gentamicin (60.5%). A total of 98 (51.6%) strains were isolated from superficial non-invasive skin and soft tissue infections, 67 (35.3%) strains from deep invasive and sterile body fluids' infections, and 25 (13.1%) strains from upper respiratory tracts' infections. Conclusion: a combination of phenotypic characteristics could still represent a reasonable Laboratory identification battery. There was no significant emerging antimicrobial resistance detected. A broad genuine spectrum of clinical infections that are caused solely by SAG was reported in our institution.

Predicting bacteremia caused by Streptococcus anginosus group: A new scoring method.

BACKGROUND: Viridans group streptococci (VGS) are the most common causative organisms of infective endocarditis. Among VGS, the Streptococcus anginosus group (SAG) is often associated with abscess formation, and delayed diagnosis leads to increased morbidity and mortality. This study aims to examine the factors associated with SAG bacteremia and develop a predictive scoring method. METHODS: This single-center retrospective case-control study of patients with VGS bacteremia compared the background and clinical characteristics between the SAG and non-SAG groups. The univariate analysis used the χ2 test and t-test. The multivariate analysis was conducted using logistic regression. RESULTS: Out of 161 patients, 95 had SAG and 66 had non-SAG bacteremia. Age >63 years: 2 points (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.64-7.54); solid tumor: 2 points (OR = 4.44, 95% CI: 1.42-6.77); C-reactive protein >7.61 mg/dL: 3 points (OR = 5.40, 95% CI: 2.49-11.72), and white blood cell count >8550/µL: 2 points (OR = 2.76, 95% CI: 1.29-2.91) were found to be independently associated with SAG bacteremia. After totaling the above variables and adding 1 point for diabetes mellitus, the area under the receiver operating curve was 0.81 (95% CI: 0.74-0.88). The sensitivity and specificity were 51% and 88%, respectively, at a cut-off of 6 points. CONCLUSIONS: In patients with VGS bacteremia, a score of 6 points or higher using this method predicts SAG with high specificity.

Streptococcus anginosus purulent pericarditis with cardiac tamponade presenting as a complication of postobstructive pneumonia.

A man in his 60s with stage 3 squamous cell carcinoma of the left lung status postchemotherapy and radiation therapy presented with mixed septic and obstructive shock with multiorgan dysfunction. Initial electrocardiogram showed sinus tachycardia and diffuse concaved ST elevation. Transthoracic echocardiogram revealed pericardial effusion with tamponade physiology. CT thorax was notable for dense left lung consolidation with pleural effusion. Emergent pericardiocentesis and percutaneous balloon pericardiotomy were performed which successfully drained 500 mL of purulent pericardial fluid. A left chest tube was placed and revealed a large volume of empyema. Both pericardial and pleural fluid cultures yielded similar strains of Streptococcus anginosus The patient was initially treated with empiric broad-spectrum intravenous antibiotics which were eventually de-escalated to intravenous ceftriaxone based on microbiology culture and sensitivity. Unfortunately, the patient developed pulseless electrical activity arrest on day 10 of intensive care unit stay and expired despite cardiopulmonary resuscitation.

Infecciones por estreptococos del grupo S. anginosus en pediatría / S. anginosus group streptococcal infections in children

Los estreptococos del grupo Streptococcus anginosus (EGA), también llamados "Streptococcus milleri", fueron reconocidos como parte de los estreptococos del grupo viridans (EGV) desde principios del siglo XX. Su rol como patógenos humanos, sin embargo comenzó a destacarse recién en la década de 1970. En esta actualización se describen aspectos microbiológicos y clínicos de los EGA. Los métodos fenotípicos de identificacón e incluso algunos genotípicos carecen de precisión para reconocer las tres especies del grupo (Streptococcus anginosus, Streptococcus constellatus y Streptococcus intermedius) e incluso pueden fallar en su clasificación a nivel de grupo. La mayoría de ellos son sensibles a los antibióticos beta-lactámicos pero son considerables los porcentajes de resistencia a macrólidos, lincosamidas y tetraciclinas. Los EGA son colonizantes habituales de las mucosas orofaríngea, intestinal y genitourinaria, pero, cada vez más frecuentemente, son reconocidos como patógenos humanos. Es ampliamente conocida su capacidad de formar abscesos en órganos sólidos, especialmente abscesos cerebrales, pulmonares y hepáticos. También producen sinusitis, empiemas y colecciones en piel y tejidos blandos, hueso, articulaciones, etc. Se han encontrado asociados con exacerbaciones pulmonares en pacientes con fibrosis quística y con enfermedad pulmonar obstructiva crónica. Producen también infecciones posteriores a mordeduras humanas, infecciones diseminadas, bacteriemia sin foco aparente y, en menor medida, endocarditis infecciosa (AU)

Streptococci from the Streptococcus anginosus group (SAG), also termed "Streptococcus milleri", were recognized as members of the viridans group streptococci (VGS) in the early 20th century. Nevertheless, their role as human pathogens only became evident in the 1970s. In this update, microbiological and clinical aspects of the SAG are described. Phenotypic and even some genotypic identification methods lack accuracy in recognizing the three species of the group (Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius) and may fail to classify them at the group level. Most of them are sensitive to beta-lactam antibiotics but rates of resistance to macrolides, lincosamides, and tetracyclines are significant. SAGs are common colonizers of the oropharyngeal, intestinal, and genitourinary mucosa, but are increasingly recognized as human pathogens. Their ability to form abscesses in solid organs, especially brain, lung and liver, is widely known. They may produce sinusitis, empyemas, and collections in skin and soft tissues, bone, joints, etc. They have also been associated with pulmonary exacerbations in patients with cystic fibrosis and chronic obstructive pulmonary disease. In addition, they may cause infections following human bites, disseminated infections, bacteremia without apparent focus, and, to a lesser extent, infective endocarditis (AU)

Screening for ß-lactam resistance by penicillin G in the Streptococcus anginosus group challenged by rare strains with altered PBPs.

BACKGROUND: Streptococcus anginosus group (SAG) strains are common pathogens causing abscesses and bacteraemia. They are generally susceptible to ß-lactams, which constitute first-line treatment. EUCAST recommends testing penicillin G susceptibility to screen for ß-lactam resistance. Isolates categorized as susceptible (negative screening) can be reported as susceptible to aminopenicillins and third-generation cephalosporins. OBJECTIVES: To assess the reliability of penicillin G resistance screening in predicting ß-lactam resistance in SAG blood culture isolates, and to investigate isolates for which this test would be unreliable. METHODS: We determined the susceptibility to penicillin G, amoxicillin and ceftriaxone of 90 SAG blood culture isolates, all with negative penicillin G resistance screening. ß-Lactam-resistant strains were sequenced and compared with susceptible reference SAG strains. RESULTS: We detected two isolates displaying ß-lactam resistance, especially to third-generation cephalosporins, despite negative screening for penicillin G resistance. For these isolates, amino acid substitutions were identified next to the essential PBP motifs SxxK, SxN and/or KS/TGS/T. Changes in these motifs have been previously linked to ß-lactam resistance in Streptococcus pneumoniae. CONCLUSIONS: Our study suggests that aminopenicillin and third-generation cephalosporin susceptibility should be determined for SAG strains in the event of severe infection as screening for penicillin G resistance might not be sufficient to detect resistance mechanisms that predominantly affect cephalosporins. The PBP sequencing of resistant SAG strains allowed us to detect amino acid changes potentially linked to ß-lactam resistance.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).