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.

Malignancy and Endocarditis: Divulging Into the Intertwined Association.

Cancer is an immunosuppressive disorder with characteristic features of unchecked cell growth, invasion, and sometimes thromboembolism leading to multiple systemic sequelae, including infective endocarditis. This article has compiled some of the crucial mechanisms by which infective endocarditis occurs in cancer patients, its risk factors, and the existing treatment interventions. It has focused on the necessity of being aware that these multiple pathogeneses are involved in the development of infective endocarditis (IE) in cancer patients, which would help delineate the risk factors associated with the condition and help physicians screen better for specific red flags. Identifying these risk factors and patient-oriented therapy, targeting the necessary elements such as causative organism, patient immune status, type of cancer, choosing evidence-based treatment modalities, and to improve the outcome of the disease in an already exasperating condition called cancer.

Shotgun whole genome sequencing of drug-resistance Streptococcus anginosus strain 47S1 isolated from a patient with pharyngitis in Saudi Arabia.

BACKGROUND: Streptococcus anginosus is an emergence opportunistic pathogen that colonize the human upper respiratory tract (URT), S. anginosus alongside with S. intermedius and S. constellatus, members of S. anginosus group, are implicated in several human infections. However, our understanding this bacterium to the genotype level with determining the genes associated with pathogenicity and antimicrobial resistance (AMR) is scarce. S. anginosus 47S1 strain was isolated from sore throat infection, the whole genome was characterized and the virulence & AMR genes contributing in pathogenicity were investigated. METHODOLOGY: The whole genome of 47S1 was sequenced by Illumina sequencing technology. Strain 47S1 genome was de novo assembled with different strategies and annotated via PGAP, PROKKA and RAST pipelines. Identifying the CRISPR-Cass system and prophages sequences was performed using CRISPRloci and PhiSpy tools respectively. Prediction the virulence genes were performed with the VFDB database. AMR genes were detected in silico using NCBI AMRFinderPlus pipeline and CARD database and compared with in vitro AST findings. RESULTS: ß-hemolytic strain 47S1 was identified with conventional microbiology techniques and confirmed by the sequences of 16S rRNA gene. Genome of 47S1 comprised of 1981512 bp. Type I-C CRISPR-Cas system and 4 prophages were detected among the genome of 47S1. Several virulence genes were predicted, most of these genes are found in other pathogenic streptococci, mainly lmb, pavA, htrA/degP, eno, sagA, psaA and cpsI which play a significant role in colonizing, invading host tissues and evade form immune system. In silico AMR findings showed that 47S1 gnome harbors (tetA, tetB &tet32), (aac(6')-I, aadK &aph(3')-IVa), fusC, and PmrA genes that mediated-resistance to tetracyclines, aminoglycosides, fusidic acid, and fluoroquinolone respectively which corresponds with in vitro AST obtained results. In conclusion, WGS is a key approach to predict the virulence and AMR genes, results obtained in this study may contribute for a better understanding of the opportunistic S. anginosus pathogenicity.

An Unusual Case of Streptococcus anginosus Endocarditis in a Healthy Host With Bicuspid Aortic Valve.

Streptococcus anginosus group (SAG) is a subgroup of viridans streptococci and can be found ubiquitously in normal human flora. SAG is known to form invasive pyogenic infection when it becomes pathogenic. Yet, SAG is a very rare cause of endocarditis, and there is a dearth of case reports on this topic. We present a rare case of native bicuspid aortic valve endocarditis secondary to S. anginosus that caused aortic insufficiency and ascending aortic aneurysm. To our knowledge, this is the first well-documented case report of community-acquired S. anginosus endocarditis on a bicuspid aortic valve in an immunocompetent patient. The patient first presented with cough that was likely due to bronchus irritation from a 5.5 x 5.2 cm ascending aortic aneurysm. He underwent aortic valve replacement with bovine bioprosthesis and ascending aortic aneurysm repairment and was treated with a two-week regimen of IV ceftriaxone and gentamicin followed by another four weeks of IV ceftriaxone. He was eventually discharged to a rehabilitation facility. SAG is usually susceptible to beta-lactam antibiotics. The prognosis of SAG infection is usually good, but progression to bacteremia carries a poor outcome.

The fibronectin-binding protein homologue Fbp62 of Streptococcus anginosus is a potent virulence factor.

Streptococcus anginosus appears to be able to adhere to cultured epithelial cells or fibronectin and this may be associated with bacterial pathogenicity. In the present study, the molecular characteristics and virulence of the fibronectin-binding protein (FBP), Fbp62, of S. anginosus were investigated in animal models to determine the role of the molecule in bacterial infection. fbp62 encodes a 549 amino acid residue with an apparent molecular mass of 62.8 kDa that lacks a membrane anchor motif and a leader peptide, suggesting that fbp62 codes for an atypical FBP. It has been observed that the S. anginosus Fbp62 is very similar to the FbpA of Streptococcus gordonii, PavA of Streptococcus pneumoniae, SmFnB of Streptococcus mutans and Fbp54 of Streptococcus pyogenes. Recombinant Fbp62 prepared from pGEX-4T-2 was found to bind to fibronectin in a dose-dependent manner and competitively inhibit the binding of S. anginosus to fibronectin. Furthermore, anti-Fbp62 antiserum abrogated the binding of S. anginosus to fibronectin. Adhesion of the isogenic mutant, Δfbp62, constructed from S. anginosus NCTC 10713 (wild-type, WT) by homologous recombination to HEp-2 cells and DOK cells was significantly weaker than that of S. anginosus WT. In addition, Δfbp62's lethality and ability to form abscesses were weaker in a mouse model of infection than in the WT strain. Taken together, these results suggest that Fbp62 is an important pathogenic factor of S. anginosus.

Sites of infection associated with Streptococcus anginosus group among children.

Streptococcus anginosus group (SAG) are parts of normal flora of the oral cavity and associated with abscess forming in various sites on the body. Although the clinical features of infections caused by each member of the SAG in adults has been reported, it has not well been known in children. The aim of this study was to clarify the site of infections associated with individual SAG species among children. Medical records from March 2010 to July 2016 were reviewed at Tokyo Metropolitan Children's Medical Center. Any SAG species (S. anginosus, S. constellatus, or S. intermedius) isolated from clinical samples and recorded in the microbiological database were included for analysis. Analysis of 52 infectious episodes found that S. anginosus was most frequently isolated from the genitourinary tract, and 73% of genitourinary tract infection was balanoposthitis. All genitourinary tract infections were associated with S. anginosus. These findings were different from those of a previous study of adults. Of all the patients, 45 patients (87%) had polymicrobial infections. More than 70% of patients infected by S. anginosus and S. constellatus were co-infected by obligate anaerobes, in comparison with only 21% of S. intermedius cases. Among the obligate anaerobes species, Bacteroides spp. was significantly accompanied with S. anginosus. Susceptibility to penicillin, ampicillin, cefotaxime, erythromycin, clindamycin, levofloxacin, and vancomycin was 100%, 100%, 100%, 77%, 89%, 97% and 100%, respectively. S. anginosus was often isolated from balanoposthitis among children.

Lincosamide resistance mediated by lnu(C) (L phenotype) in a Streptococcus anginosus clinical isolate.

OBJECTIVES: Unique resistance to lincosamides (L phenotype) due to the production of nucleotidyltransferases (Lnu) is uncommon among Gram-positive bacteria. The aim of the study was to characterize the L phenotype in a clinical isolate of the Streptococcus milleri group. METHODS: The strain UCN93 was recovered from neonatal specimens and from the mother's vaginal swab. Identification was confirmed by sequencing of the sodA gene. Antimicrobial susceptibility testing was carried out by the disc diffusion method, while MICs were determined using the agar dilution method. Screening for lnu(A), lnu(B), lnu(C) and lnu(D) genes was performed by PCR. Genetic environment and support were determined by thermal asymmetric interlaced PCR and PCR mapping. The transfer of lincomycin resistance was also attempted by conjugation. RESULTS: UCN93 was unambiguously identified as Streptococcus anginosus. It was susceptible to all tested antibiotics, except lincomycin (MIC, 8 mg/L) and tetracycline (2 mg/L). The lnu(C) gene was found to be responsible for the L phenotype. It was shown that lnu(C) was associated with a gene coding for a transposase within a structure similar to the transposon MTnSag1, described once in Streptococcus agalactiae. Since MTnSag1 was found to be mobilized by Tn916 and S. anginosus UCN93 harboured a Tn916 transposon, several attempts at transfer were performed but they all failed. The lnu(C)-containing genetic element was inserted into a chromosomal intergenic sequence of S. anginosus. CONCLUSIONS: Since lnu(C) has been detected in only one S. agalactiae clinical isolate so far, this is its second description among clinically relevant streptococci.

Antibiotic susceptibility in mutans streptococci and Streptococcus anginosus isolated from dental plaque / 대한치과보존학회지

The aim of this study was to investigate the susceptibility of mutans streptococci (S. mutans and S. sobrinus) and Streptococcus anginosus, for seven antibiotics, penicillin G, amoxicillin, ciprofloxacin, cefuroxime, erythromycin, bacitracin, and vancomycin. The minimum inhibitory concentration (MIC) of seven antibiotics against 3 species (type strains) of mutans streptococci and S. anginosus, 10 strains (wild type) of S. mutans, 7 strains (wild type) of S. sobrinus, and 11 strains (wild type) of S. anginosus, were measured by broth dilution method. All of the type strains of mutans streptococci and S. anginosus had the same susceptibility for penicillin G, amoxicillin, cefuroxime and bacitracin. Type strain of S. anginosus was sensitive in ciprofloxacin, but those of mutans streptococci were not. All of the clinical isolates of mutans streptococci and S. anginosus had the same susceptibility for the seven antibiotics. Our data reveal that mutans streptococci and S. anginosus have similar antibiotic-resistant character. In addition, these results may offer the basic data to verify the antibiotic-resistant mechanism of mutans streptococci and S. anginosus.