Population genomics of Streptococcus mitis in UK and Ireland bloodstream infection and infective endocarditis cases.

Streptococcus mitis is a leading cause of infective endocarditis (IE). However, our understanding of the genomic epidemiology and pathogenicity of IE-associated S. mitis is hampered by low IE incidence. Here we use whole genome sequencing of 129 S. mitis bloodstream infection (BSI) isolates collected between 2001-2016 from clinically diagnosed IE cases in the UK to investigate genetic diversity, antimicrobial resistance, and pathogenicity. We show high genetic diversity of IE-associated S. mitis with virtually all isolates belonging to distinct lineages indicating no predominance of specific lineages. Additionally, we find a highly variable distribution of known pneumococcal virulence genes among the isolates, some of which are overrepresented in disease when compared to carriage strains. Our findings suggest that S. mitis in patients with clinically diagnosed IE is not primarily caused by specific hypervirulent or antimicrobial resistant lineages, highlighting the accidental pathogenic nature of S. mitis in patients with clinically diagnosed IE.

Endogenous endophthalmitis caused by Streptococcus mitis: A case report.

RATIONALE: Endogenous endophthalmitis is a rare disease caused by hematogenous intraocular metastasis of bacteria from an infectious source. Diagnosing endogenous endophthalmitis is challenging for non-ophthalmologists. However, ophthalmic diseases can cause irreversible vision loss, making prompt diagnosis and treatment critical. Here we present a rare case of endogenous endophthalmitis initially misdiagnosed as a cataract. PATIENT CONCERNS: An 84-year-old Japanese man presented to the emergency department with fever and dysmotility. The patient was aware of a left subconjunctival hemorrhage and cloudy cornea upon arrival at the hospital, but he misunderstood it as a fall-induced subconjunctival hemorrhage and age-related cataracts. DIAGNOSES: On the day following admission, petechial hemorrhage on the eyelid conjunctiva and the detection of Streptococcus mitis in the blood culture results led us to suspect endophthalmitis rather than cataracts. A definitive diagnosis of endophthalmitis was made through ophthalmologic examinations, and endophthalmitis was considered secondary to endocarditis. INTERVENTIONS: Subsequently, antimicrobial treatment was continued. OUTCOMES: However, the patient developed myocardial infarction and died on the ninth day of hospitalization. LESSONS: Two important lessons were learned from the examination of this case of endogenous endophthalmitis caused by S mitis. First, endophthalmitis and cataracts can be misdiagnosed. Because the symptoms of endophthalmitis and cataracts, such as decreased vision, photophobia, and blurred vision, are similar, the eye must be cautiously examined. Second, endocarditis caused by S mitis may lead to endogenous endophthalmitis. Although S mitis is not pathogenic, endogenous endophthalmitis may occur in patients with certain risk factors, such as older age, cancer, and immunosuppression.

Streptococcus mitis enhances metal-induced apoptosis in reconstructed human gingiva but not skin.

BACKGROUND: Commensal bacteria colonizing oral mucosa and skin play an essential role in maintaining host-microbiome homeostasis. It is unknown whether cytotoxicity resulting from metal ions leaching from medical devices may be influenced by commensal microbes. OBJECTIVE: Determine whether the extent of apoptosis triggered by nickel or titanium ions is influenced by Streptococcus mitis and whether apoptosis occurs via the intrinsic or extrinsic apoptosis pathway. METHODS: Reconstructed Human Gingiva (RHG) and Skin (RHS) were topically exposed to titanium or nickel salts in the presence or absence of S. mitis. Cytotoxicity and apoptosis were assessed by histology, immunohistochemistry, TUNEL assay, and Western Blot. RESULTS: S. mitis alone resulted in negligible cytotoxicity. After metal exposure, localized apoptosis was observed in the epithelium and fibroblasts within the lamina propria hydrogel of both RHG and RHS. S. mitis enhanced metal-mediated apoptosis in gingiva but not in skin. Apoptosis was mediated via the extrinsic pathway caspase 8. Activation of the execution phase of apoptosis occurred via caspases 3 and 7, and PARP-1. CONCLUSION: Our study supports the finding that metals have irritant, cytotoxic properties resulting in apoptosis when leaching into skin or gingiva. Particularly for gingiva, commensal microbes exaggerate this detrimental effect.

Bacterial adhesion and surface properties of computer-aided design-computer-aided manufacturing restorative materials.

PURPOSE: This study aimed to evaluate the surface properties and bacterial adhesion of computer-aided design-computer-aided manufacturing (CAD-CAM) restorative materials. METHODS: Four CAD-CAM resin-based blocks (Vita Enamic, Shofu block HC, Cerasmart [CS] and Lava Ultimate [LU]) and a leucite-reinforced glass ceramic block (IPS Empress CAD) were used in the present study. Specimens prepared with dimensions of 10 × 10 × 1 mm were polished. Surface characteristics were assessed with hydrophobicity and surface free energy (SFE) analysis. Surface roughness was measured using a profilometer, and elemental and topographic evaluations were performed with SEM-EDX analysis. After being kept in artificial saliva for 1 h, Streptococcus mutans (S. mutans) and Streptococcus mitis (S. mitis) were incubated separately in 5% CO2 atmosphere at 37°C for 24 h. The adhered bacteria were counted as ×108 CFU/mL. RESULTS: Surface roughness, contact angle and SFE measurement values were found to be in the range of 0.144-0.264 Ra, 28.362°-70.074° and 39.65-63.62 mN/m, respectively. The highest adhered amount of S. mutans was found in CS and the lowest in LU, while there was no significant difference between the amounts of adhered S. mitis. CONCLUSION: Despite differences in the surface properties of the materials used for the study, the materials exhibited identical properties with respect to bacterial adhesion.

Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations.

Evaluation of the apportionment of genetic diversity of human bacterial commensals within and between human populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among human populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oro-nasopharyngeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher ancestral bacterial population effective size (Ne) in S. mitis, whose genomic variation has been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral bacterial population. Strikingly, both species show limited differentiation among human populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.

Clinical isolates of Streptococcus mitis/oralis-related species with reduced carbapenem susceptibility, harboring amino acid substitutions in penicillin-binding proteins in Japan.

Streptococcus mitis/oralis group isolates with reduced carbapenem susceptibility have been reported, but its isolation rate in Japan is unknown. We collected 356 clinical α-hemolytic streptococcal isolates and identified 142 of them as S. mitis/oralis using partial sodA sequencing. The rate of meropenem non-susceptibility was 17.6% (25/142). All 25 carbapenem-non-susceptible isolates harbored amino acid substitutions in/near the conserved motifs in PBP1A, PBP2B, and PBP2X. Carbapenem non-susceptibility is common among S. mitis/oralis group isolates in Japan.

Developing multispecies quorum-sensing modulators based on the Streptococcus mitis competence-stimulating peptide.

Bacteria utilize quorum sensing (QS) to coordinate many group behaviors. As such, QS has attracted significant attention as a potential mean to attenuate bacterial infectivity without introducing selective pressure for resistance development. Streptococcus mitis, a human commensal, acts as a genetic diversity reservoir for Streptococcus pneumoniae, a prevalent human pathogen. S. mitis possesses a typical comABCDE competence regulon QS circuitry; however, the competence-stimulating peptide (CSP) responsible for QS activation and the regulatory role of the competence regulon QS circuitry in S. mitis are yet to be explored. We set out to delineate the competence regulon QS circuitry in S. mitis, including confirming the identity of the native CSP signal, evaluating the molecular mechanism that governs CSP interactions with histidine kinase receptor ComD leading to ComD activation, and defining the regulatory roles of the competence regulon QS circuitry in initiating various S. mitis phenotypes. Our analysis revealed important structure-activity relationship insights of the CSP signal and facilitated the development of novel CSP-based QS modulators. Our analysis also revealed the involvement of the competence regulon in modulating competence development and biofilm formation. Furthermore, our analysis revealed that the native S. mitis CSP signal can modulate QS response in S. pneumoniae. Capitalizing on this crosstalk, we developed a multispecies QS modulator that activates both the pneumococcus ComD receptors and the S. mitis ComD-2 receptor with high potencies. The novel scaffolds identified herein can be utilized to evaluate the effects temporal QS modulation has on S. mitis as it inhabits its natural niche.

Genomic Features and Comparative Genomic Analysis of Streptococcus sp. v1. nov., Isolated from an Endophthalmitis Patient.

Endophthalmitis is an acute inflammatory intraocular condition that can cause permanent vision loss. The treatment strategy and visual outcome partly depend on the identification of the agents of pathogens. In this study, metagenomic sequencing was conducted to investigate the microbial and antibiotic resistance genes (ARGs) composition in the vitreous (intraocular body fluid) of an endophthalmitis patient, who progressed rapidly and accompanied by severe pain. Metagenomic sequencing data revealed that the vitreous sample was predominated by Streptococcus, with a low-diversity microbiome in the vitreous. This strain harbor's the ARGs mainly against beta-lactam, macrolide-lincosamide-streptogramin, and multidrug. Additionally, metagenome-assembled genome sequence of Streptococcus sp. v1. nov. was identified. The Tetra Correlation Search (TCS) analysis uncovered that the closest relative of the Streptococcus sp. v1. nov. was Streptococcus mitis SK321. Pan/core genome analysis for Streptococcus sp. v1. nov. and TCS top 25 hits strains revealed that most unique genes of Streptococcus sp. v1. nov. were linked to ATP-binding cassette transport system, which could indicate unique virulence and pathogenic potentials of Streptococcus sp. v1. nov. In addition, a total of 7 virulence factors were identified, and the overwhelming of them were classified into "offensive virulence factors". The high pathogenicity of Streptococcus sp. v1. nov. could be a reason for the patient's rapid disease progression. Our study was first isolated an ocular pathogen with highly virulent based on metagenomic sequencing and bioinformatics analysis, which has important reference value for revealing the composition and genome characteristics of pathogens in endophthalmitis patient in the future.

Bacterial multispecies interaction mechanisms dictate biogeographic arrangement between the oral commensals Corynebacterium matruchotii and Streptococcus mitis.

IMPORTANCE: As the microbiome era matures, the need for mechanistic interaction data between species is crucial to understand how stable microbiomes are preserved, especially in healthy conditions where the microbiota could help resist opportunistic or exogenous pathogens. Here we reveal multiple mechanisms of interaction between two commensals that dictate their biogeographic relationship to each other in previously described structures in human supragingival plaque. Using a novel variation for chemical detection, we observed metabolite exchange between individual bacterial cells in real time validating the ability of these organisms to carry out metabolic crossfeeding at distal and temporal scales observed in vivo. These findings reveal one way by which these interactions are both favorable to the interacting commensals and potentially the host.

Streptococcus Mitis Endocarditis Associated with Early Gastric Carcinoma.

We report a case of Streptococcus mitis endocarditis associated with early gastric carcinoma. A 71-year-old man who had been diagnosed with aortic regurgitation (AR) two years previously was referred for valve surgery and evaluation of elevated inflammatory markers. Four months previously, atrophic gastritis, early gastric adenocarcinoma, and colon polyp had been identified in the patient during endoscopy. However, Helicobacter pylori testing was negative. On admission, he had no dental diseases or recent oral procedures. Echocardiography demonstrated severe AR and mobile vegetation on the aortic valve. Magnetic resonance imaging revealed cerebral embolism and spondylodiscitis. Blood cultures grew Streptococcus mitis. At surgery, destruction of the left cusp with vegetation and a perforation of the non-coronary cusp were found; in addition, aortic valve replacement was performed. Although the association between Streptococcus bovis bacteremia and colon neoplasm is well recognized, the association between Streptococcus mitis endocarditis and gastrointestinal carcinoma should also be kept in mind.