How Are Animals Tested For Brain Abscesses

Introduction

Streptococcus intermedius is a β-hemolytic Gram-positive coccus and member of the Streptococcus anginosus group (SAG), as well referred to every bit the "Streptococcus milleri" (Facklam, 2002). Members of the SAG are office of the normal microbiota and are found at various mucosal sites in the respiratory, gastrointestinal, and genitourinary tracts with variable carriage levels (Gossling, 1988). However, members of the SAG are medically important considering they are ofttimes encountered in invasive suppurative infections in numerous torso sites, causing liver and brain abscesses, dentoalveolar infections, and infective endocarditis (Jacobs et al., 1995). Members of the SAG have been identified every bit the most common organism existence isolated from brain (Prasad et al., 2006; Sibley et al., 2012) and liver abscesses (Sibley et al., 2010) and thoracic empyema (Ahmed et al., 2006). Moreover, they arm-twist pulmonary exacerbation and worsen the illness outcome in patients with cystic fibrosis (Parkins et al., 2008). South. anginosus has been associated with intra-abdominal and gastrointestinal tract infections, whereas S. intermedius has been isolated more than frequently from purulent head and neck specimens and key nervous system infections (Whiley et al., 1992; Bantar et al., 1996; Clarridge et al., 2001). An association between S. constellatus and thoracic infections has been previously suggested (Jacobs et al., 1995). Two more recent studies that investigated possible associations between species of SAG bacteria and specific clinical syndromes on 245 and 76 bacterial isolates, respectively, did non show whatsoever significant correlation betwixt the species and the site of infection (Siegman-Igra et al., 2012; Junckerstorff et al., 2014). The simply association the authors institute was a higher relative representation of Southward. constellatus amongst claret culture isolates (Siegman-Igra et al., 2012). Very few studies also evaluated SAG bacterial infections and clinical outcomes, including morbidity and bloodshed, with varying conclusions (Jacobs et al., 1994, 1995; Casariego et al., 1996; Siegman-Igra et al., 2012; Junckerstorff et al., 2014). Bloodshed rates among patients with SAG-associated bacteremia range between ten and 16%. Jacobs et al. (1994) examined nineteen cases of SAG-associated bacteremia and found that 78.9% (n = fifteen) were caused by S. anginosus of which 33.3% (n = v) died. In another written report, they observed a xvi% mortality rate among patients with SAG-associated bacteremia (Jacobs et al., 1995). Casariego et al. (1996) reviewed thirty cases of SAG-associated bacteremia and observed a 10% (northward = 3) mortality rate among patients infected with S. constellatus, while half dozen.vii% (due north = two) of patients were infected with South. anginosus and survived. On the other hand, Siegman-Igra et al. (2012) establish that S. anginosus accounted for 67.8% (north = 19) of 28 SAG-associated bacteremia with a 15.viii% (due north = three) mortality. It is noteworthy that patients with invasive South. intermedius infections had significantly longer infirmary stays compared to patients infected with South. anginosus and significantly higher bloodshed rates than patients infected with S. constellatus (Junckerstorff et al., 2014).

Due south. intermedius bacteremia and liver abscesses have been frequently reported in patients following recent dental manipulation. Since Due south. intermedius is part of the commensal oral flora in humans, dental cleaning can result in bacteremia and seeding of the liver via the hematogenous road fifty-fifty in the absence of an active oral infection (Livingston and Perez-Colon, 2014).

The taxonomic grouping of SAG members has long been debatable (Coykendall et al., 1987), and this is partly due to varying nomenclature (Facklam, 2002) and partly due to the low resolution provided by traditional phenotypic identification methods (Jones, 1978; Kilian et al., 1989; Whiley et al., 1990, 1999). More recently, it has been shown that the SAG consists of three distinct species: S. anginosus, Southward. intermedius, and Southward. constellatus (Jensen et al., 2013). S. constellatus was further divided into three subspecies (subsp constellatus, subsp pharynges, and subsp viborgensis), and S. anginosus was divided into 2 subspecies (subsp anginosus and subsp whileyi) based on the use of seven core housekeeping genes (Jensen et al., 2013).

Despite existence phenotypically various, members of the SAG share few common characteristics, such as having a ho-hum growth rate, a distinctive "caramel smell," the power to hydrolyze arginine, the ability to produce acetoin from glucose, and the disability to ferment sorbitol (Gossling, 1988). They too have a variable Lancefield serogrouping; a system of group streptococci based on antigenic differences in C carbohydrates located in their cell wall. S. anginous are typically Lancefield types A, C, F, or Chiliad, S. constellatus are typically Lancefield types C, F, or no antigen, and Southward. intermedius are generally not typeable using the Lancefield method. Almost half of all human SAG clinical isolates are of the Lancefield F blazon (Grinwis et al., 2010).

A search on PubMed Central revealed that SAG members are clearly underrepresented compared to other medically relevant streptococci with the least represented being on S. constellatus followed by S. anginosus and S. intermedius (Effigy 1A). Very few contempo studies were published correlating clinical outcomes, morbidity, and mortality in SAG-infected patients, while the prediction of the disease effect in S. intermedius-infected patients remains unrealistic. Also, the advent of whole-genome sequencing (WGS) has provided in-depth data into S. intermedius genome organization, virulence, and secretion systems that might help in highlighting specific genetic markers and single point variants in various SAG members, as demonstrated in the work done by Issa et al. (2019). Agreement the diverse genetic components contributing to abscess development could also help in finding novel targets for therapy and vaccine development. Given the caveats in our understanding of S. intermedius pathobiology, prediction of illness outcome, and genome content, this review has summarized our current knowledge on the Southward. intermedius pathogen, its various identification methods, known virulence factors, and regulation of cistron expression involved in abscess development and whole-genome provided insights. Additionally, nosotros take summarized 101 recent case reports of Southward. intermedius infections with full description of patients' metadata, clinical profiles, symptoms, neurological results, imaging results, isolation sites, co-infections, abscess localization, prescribed antibiotics to care for the infection, and disease upshot obtained from PubMed in an attempt to observe patterns associated with the infection. This combined data highlights the gaps in our agreement of S. intermedius pathogenesis and suggests future research directions to unveil the factors contributing to abscess evolution.

Figure one. Representative members of streptococci and SAG members and the distribution of the genome assemblies. (A) Word cloud showing the medically relevant streptococci and SAG members based on a PubMed Central information (last accessed: July 3rd, 2019). (B) Distribution of the genome assemblies on NCBI for SAG members and other medically relevant streptococci (terminal accessed on 08/05/2019); SAG members are depicted in crimson.

Identification

Due to the lack of reliable phenotypic differences betwixt members of the SAG, these streptococci are rarely identified to the species level in clinical microbiological laboratories. One of the basic phenotypic characteristics for clinical laboratories is their reaction on claret agar plates. Hemolysis is used as a guide for managing patients and gives hints into the classification of the bacterium to the species level (Facklam, 2002). Ane step further in the identification and speciation of the SAG members could be performed using commercially bachelor identification kits, such as API 20 Strep (bioMérieux, Lyon, France).

Real-time PCR, mass spectrometry (MALDI-TOF-MS), likewise as conventional PCR assays were also used to differentiate between individual species of the SAG (Takao et al., 2004; Friedrichs et al., 2007; Desar et al., 2008; Olson et al., 2010; Reißmann et al., 2010). The PCR distension covering an 819 bp fragment of the ily gene encoding intermedilysin and its 3'-flanking region was shown to be specific for Southward. intermedius in contrast to other SAG members (Goto et al., 2002). Other target genes included 16S rRNA, cpn60, and rpoB (Olson et al., 2013). These, withal, might non provide enough discriminatory power between closely related species. For example, 16S rRNA gene-based phylogeny suffered from depression resolution (Schouls et al., 2003), and information technology was not a suitable approach to differentiate S. intermedius from Southward. constellatus (Issa et al., 2019). On the other hand, cpn60 outperformed both 16S rRNA and rpoB in differentiation between individual strains (Olson et al., 2013). Results obtained from single locus genetic markers might not be as reliable every bit those obtained with multiple genetic loci. In fact, a multi-locus sequence assay (MLSA) approach of concatenated sequences of vii housekeeping genes was shown to be more than promising in identifying well-resolved species clusters (Bishop et al., 2009; Jensen et al., 2013). Bishop et al. (2009) collected seven housekeeping gene sequences from 420 streptococci to produce a viridans group database and adult a publicly bachelor website and software for electronic taxonomy¹. The vii targeted genes were map encoded for a methionine aminopeptidase, pfl, a pyruvate formate lyase, ppaC, an inorganic pyrophosphatase, pyk, a pyruvate kinase, rpoB, an RNA polymerase subunit, soda, a superoxide dismutase, and tuf, an elongation factor Tu (Bishop et al., 2009). Jensen et al. (2013) used the MLSA-based arroyo and performed a phylogenetic analysis of concatenated sequences of the seven housekeeping genes in 123 SAG isolates. As a result, they were able to differentiate between seven distinct and coherent clusters in SAG and showed that unmarried gene analyses are often invalid as they suffered from allele sharing between species (Jensen et al., 2013).

The appearance of WGS has provided, still, a better resolution and discriminatory power between closely related organisms at the species and strain levels past looking into the aggregating of single-nucleotide polymorphisms (SNPs), core genome conservation, virulence potential, horizontally transferred genetic material, and microevolution within the host (Olson et al., 2013). This approach was better at comparing and identifying the isolates at the species and strain level (Issa et al., 2019). Although 42 genome assemblies of South. intermedius are currently bachelor on the NCBI database (last accessed on 08/05/2019), S. intermedius nevertheless remains under-represented compared to other SAG members and other medically relevant streptococci (Figure 1B).

Clinical Cases

Case reports of South. intermedius infections were collected from PubMed (terminal accessed on 08/05/2019) occurring over a 23-twelvemonth period (1996–2019). A total of 101 cases with available patient metadata were retained, 85.1% (n = 86) of which were reported after the yr of 2015, 12.ix% (n = 13) between 2001 and 2014, and 2.0% (n = 2) prior to 2001. The following demographic and clinical data was obtained from the literature: patient'south historic period, sex, yr of infection (if not bachelor the publication date was used), country of isolation, clinical contour (including previous relevant pathologies, surgeries, dental manipulation, etc.), symptoms, neurological results when bachelor (including sensory losses, quadriplegia, numbness, weakness, move restriction etc.), imaging results [mainly computed tomography (CT)], isolation source of the bacterium, coinfection with other bacteria, presence or absence of an abscess and its localization, prescribed antibiotics, and outcome of the disease (recovery or decease) (Table i and Supplementary Table S1).

Table ane. Characteristics of included South. intermedius case reports.

Patient Age, Sex, and Location

Patients' ages ranged from five to 83 years old. The hateful patient age was 45± 24 years old. Most cases of S. intermedius infection were identified in patients within older age groups of 61–70 (17.viii%; n = 18), followed by 51–lx (16.eight%; n = 17) and 14.9% (n = 15) for 71–80-year-old patients. Only ii cases (2.0%) were >80 years onetime. The remaining of the cases were 0–x years old (9.9%; n = ten), eleven–20 years old (12.9%; n = 13), 21–30 years old (ix.9%; due north = 10), 31–xl years old (viii.nine%; due north = 9), and 41–l years onetime (half-dozen.ix%; n = 7). Notably, the cases included approximately twice as many males as females (M: 63.4%; n = 64 and F: 36.6%; n = 37), with the mortality rate being 6.9% (due north = 7). Nigh reported cases were from the United States (38.six%; northward = 39), followed by Europe (32.7%; north =32), Eastern asia (19.viii%; due north = twenty), the Centre East and Due north Africa (4.9%; n = 5), Canada (iii.0%; due north = 3), and Commonwealth of australia and Republic of chile (1.0%; n = 1, each) (Figure 2). No age- or geo-specific design for abscess localization were detected (Figure 2, iii).

Figure 2. Worldwide reported S. intermedius cases. Dots were colored co-ordinate to the abscess localizations.

Effigy iii. Distribution of instance reports based on patients' age categories, sex, and abscess localization. Thousand, male; F, Female.

In accordance with our findings, a retrospective analysis of a hospital's admissions betwixt 2004 and 2009 in Commonwealth of australia showed male person predominance of S. intermedius infections comprising 67% (n = 6) of all cases as opposed to 33% (n = 3) of infections affecting females. The mean patient age was reported to be college (average = 59.8 years) (Junckerstorff et al., 2014).

Symptoms

Upon admission, most patients showed primarily symptoms of intermittent fever and consequent headaches. These symptoms classically imply a potential brain abscess (Brouwer et al., 2014). Nonetheless, proper imaging techniques are needed to diagnose and localize a brain abscess. Claret tests for the C-reactive protein and WBC count were elevated and indicative of an infection.

Take chances Factors

Underlying adventure factors for S. intermedius infections were detected among patients. Well-nigh patients experienced a previous dental manipulation (xviii.8%; north = 19) or suffered from sinusitis (11.9%; n = 12). Other chance factors included a history of diabetes (7.9%; north = 8), heavy alcohol consumption (7.9%; n = 8) congenital middle disease and middle-related conditions (seven.9%; n = eight), and cancer (half dozen.9%; n = vii). Patients also reported of undergoing surgery (4.9%; n = v), having asthma (four.0%; n = iv), suffering from falls (4.0%; n = 4), smoking (4.0%; n = 4), and employ of drugs (iii.0%; n = 3).

A previous study identified the primary risk factors of SAG infections (Suzuki et al., 2016). Solid tumors were the almost comorbid (32.1%, n = 25), followed by diabetes mellitus (xviii.0%, n = xiv), eye failure, liver disease, dementia (each 12.8%, n = 10), hemiplegia, cerebral vascular disease (each eleven.five%, n = 9), myocardial infarction (seven.7%, northward = half-dozen), collagen disease, peripheral artery illness (each 6.iv%, northward = 5), chronic respiratory disease (v.1%, n = 4), peptic ulcer affliction, chronic kidney disease (3.ix%, n = 3), and leukemia (1.3%, due north = 1) (Suzuki et al., 2016). In light of these reports and our findings, more attention has to be given to dental manipulations, sinusitis, and diabetes mellitus as underlying factors for Due south. intermedius infections.

Abscess Formation and Detection

S. intermedius was mainly isolated from pus (34.7%; due north = 35), encephalon (16.8%; n = 17), blood (fourteen.9%; northward = 15), and cerebrospinal fluid (6.nine%; north = 7). Isolation from the cornea, ear, oral cavity, nose, esophagus, heart, and lung were also reported. Virtually all infections (98.0%, n = 99) were associated with abscess development, detected through various imaging approaches including computed tomography (CT), scans and magnetic resonance imaging (MRIs). Brain abscesses were the most arable (41.6%), followed by lung (12.9%) equally well as liver and spine (7.9% each) (Effigy 3).

Similarly, Kobo et al. (2017) reported greater Due south. intermedius isolation from pyogenic infections (86.1%, n = 31) as compared to non-pyogenic infections (13.9%, north = 5). Another study correlated specific body sites with S. intermedius infection which prominently afflicted the central nervous system (62.1%, north = 18), followed by abdominal or pelvic sites (xiii.eight%, north = 4), skin, soft tissues, os (13.8%, n = iv), and head and neck infections (x.3%, n = iii) (Whiley et al., 1992).

Handling

Abscess drainage and surgery remained as the only interventions to limit the abscess and were performed in 32.seven% (n = 33) and 22.8% (north = 23) of the cases, respectively. The use of antibiotics was mentioned in 78.2% (n = 79) of the studied case reports. Antibiotic treatments were administered for up to 6 weeks after discharge from the hospital. A variety of antibiotics were prescribed to treat the patients with combination therapies prescribed in 77.ii% (due north = 61), and a single antibody treatment was prescribed in 25.3% (northward = 20) of the cases. Upon admission, nigh commonly prescribed antibiotic regimens were a combination of ceftriaxone and metronidazole alone (half-dozen.3%; north = v) or the latter two combined with vancomycin (vi.3%; n = v). Interestingly, the prescribed antibiotic regimen was inverse during the class of infection for 32.nine% (n = 26) of the patients; the antibody treatment prescribed upon infirmary access was most often changed to include metronidazole (xxx.8%; n = 8), ceftriaxone (19.2%; northward = five), or meropenem (xv.4%; n = 4). During the entire form of treatment, the about ordinarily prescribed antibiotic was metronidazole (44.three%; north = 35) followed by: ceftriaxone (39.ii%; n = 31), vancomycin (22.8%; n = 18), penicillin (xv.2%; n = 12), clindamycin (12.7%; n = 10), meropenem (13.9%; n = 11), and ampicillin (12.vii%; n = x). Subsequently patients were ordinarily exposed to i–6 antibiotics during the elapsing of handling with 4.9% (due north = 4), 8.6% (n = vii), eleven.one% (due north = 9), 17.2% (n = 12), 28.4% (n = 23), and 25.ix% (n = 21) patients beingness prescribed half dozen, five, four, 3, two, or one antibody, respectively. With no published guidelines or recommendations to treat SAG, the option and elapsing of handling remains unclear (De Louvois et al., 2000; Yakut et al., 2015). Nevertheless, the excessive use of antibiotics is alarming and favors the emergence of drug resistance especially with vancomycin and carbapenems (meropenem) (Mohammadi et al., 2019).

Prior retrospective studies past Clarridge et al. (2001) suggested the necessity of CT-guided aspiration or extensive surgery in both the diagnosis and handling of S. intermedius. Furthermore, patients in this written report were administered penicillin or its enhanced form every bit a single-drug therapy or a combination of drugs in cases of polymicrobial infections. Subsequent effective handling outcomes suggested microbial susceptibility to the antibody used (Clarridge et al., 2001).

Co-infection

Co-infection with microorganisms other than S. intermedius was detected in 29.7% of the studied cases (northward = 30). Other SAG members were ordinarily detected such equally S. anginosus (ten.0%; n = 3) and South. constellatus (13.iii%; north = 4) in addition to other streptococci, such equally non-enterococcal group D streptococci, Due south. viridans, South. salivarus, and South. pneumoniae. Other normally detected organisms included Actinomyces species (13.3%; n = 4) and Fusobacterium species (6.7%; due north = 2). Staphylococcus species were found in 13.3% (n = four) of co-infection cases.

Previously Furuichi and Horikoshi (2018), revealed a college occurrence of polymicrobial infections (71.iv%, n = 10) and included anaerobic microorganisms, mainly Peptostreptococcus spp. (14%, n = 2), Bacteroides spp. (7%, north = 1), Prevotella spp. (7%, due north = i), and Porphyromonas spp. (7%, due north = 1). Other gram-positive bacteria were isolated and normally identified as Staphylococcus species (21%, n = 3), cocci (29%, north = four), and rods (7%, northward = 1). Bacterial cultures as well revealed gram-negative cocci (21%, n = 3), Haemophilus influenzae (xiv%, due north = 2), and Eikenella corrodens (7%, n = 1).

Virulence and Abscess Formation

SAG members have been identified every bit the most common organisms isolated from brain abscess (Prasad et al., 2006; Sibley et al., 2012), liver abscess (Sibley et al., 2010), and empyema (Ahmed et al., 2006). S. intermedius has been mostly associated with central nervous system infections, particularly brain abscesses (Whiley et al., 1992). Currently, the verbal genetic components leading to brain abscess development in some strains of South. intermedius, but non others, are not well understood. The known factors contributing to S. intermedius invasion and encephalon abscess formation are summarized in Figure 4.

Effigy 4. Major Southward. intermedius virulence factors and regulation of factor expression involved in encephalon abscess formation. Post-obit Due south. intermedius infection, tissue harm is caused past the hydrolytic activeness of hyaluronidase (hyl) and proinflammatory cytokine build-up from the bounden of surface proteins to ECM components and macrophage stimulation by histone-like DNA binding proteins (HLPs). Hyl likewise degrades the hyaluronate constituent of connective tissues, which serves every bit a bacterial nutrient. Antigens I/Ii surface proteins (fbp54 and lmb) bind to fibronectin and laminin of the ECM, which stimulates interleukin 8 release from monocytes followed by neutrophil chemotaxis. Adhesion is besides mediated past surface proteins (psaA), enolase (eno), and pullulanase (pulA). S. intermedius escapes host immunological defenses through the expression of lymphocyte-apoptotic superantigens and biofilm germination monitored past the product of the luxS gene, antoinducer-ii, and hyaluronidase activity. Invasion is ensured by a complete Streptococcus Invasion locus (sil) system and a homolog of internalin A. Replication and abscess formation are immune through the polysaccharidic capsular inhibition of phagocytic polymorphonuclear neutrophils. Intermedilysin (ILY) and sialidase A (NanA) are Southward. intermedius-specific virulence factors. ILY binds to the human complement regulator CD59 (hCD59) and creates pores in membranes of red blood cells allowing for necrosis. NanA releases sialic acid moieties from sugar chains nowadays in the environment and the surface of bacteria to straight inter-bacterial and host-bacterial interactions. Regulation of gene expression depends on carbohydrate supply. Under glucose-poor conditions (calorie-free bluish), multi-substrate glycosidase A (MsgA) and NanA dethrone glycans in the human serum to release N-acetylneuraminic acid and galactose. Galactose inhibits the lactose phosphotransferase organization repressor (LacR), an ILY silencer, resulting in a constitutive ILY expression and a positive feedback loop for MsgA and NanA expression. Under glucose-rich weather condition (red), the catabolite command protein (CcpA) represses ILY expression via either binding to the ily promoter on the catabolite repressible chemical element (cre) or controlling the concentration of ily transcriptional regulators. ILY, MsgA, and NanA activities are too reduced by immunoglobulins in the homo plasma. The luxS pathway (violet) constitutively increase ILY and hyl expression and the ILY hemolytic activity but not that of hyaluronidase (figure created with BioRender).

Antigens I/II

The onset of S. intermedius brain abscess germination first begins with tissue damage that precedes bacterial colonization. This occurs by bounden to human fibronectin and laminin components of the extracellular matrix (ECM) through antigens I/II surface proteins, and they are coded by fbp54 and lmb, respectively (Baddour, 1994; Petersen et al., 2001). The immunological response to binding is manifested past Interleukin viii (IL-viii), released from monocytes, which in turn activates neutrophil chemotaxis and contributes to proinflammatory cytokine build-up causing tissue damage (Kielian et al., 2001; Petersen et al., 2001). Cytokines are too released from human macrophages upon stimulation by histone-like DNA binding proteins (HLPs), and this alters the nucleoid architecture to command cistron transcription (Liu et al., 2008). Adhesion to the ECM is as well facilitated by the surface protein (psaA), enolase (eno) for plasminogen binding, and pullulanase (pulA) (Issa et al., 2019). The PsaA protein ortholog in Due south. pneumoniae has been shown to bind to the adhesion molecule E-cadherin (Anderton et al., 2007). Likewise, α-Enolase is the major plasmin- and plasminogen-binding poly peptide of streptococci and was associated with bounden to mucin in S. mutans (Ge et al., 2004). Finally, pulA was linked to the strepadhesin activity of S. pyogenes (Hytönen et al., 2003).

Hyaluronidase

Due south. intermedius farther expresses hydrolytic enzymes responsible for tissue liquefaction and pus germination, such as hyaluronidase (hyl), chondroitin sulfatase, and deoxyribonuclease. Hyaluronidase is also a growth cistron that mobilizes low molecular weight nutrients in the host to be used by this bacterium (Ruoff and Ferraro, 1987; Willcox et al., 1995; Takao et al., 1997). Consequently, college hyaluronidase concentrations are observed in deeper abscesses as its expression depends on substrate availability of hyaluronate (Homer et al., 1997). Hyaluronidase facilitates bacterial and toxin spread in tissues through increased connective tissue permeability and decreased footing substance viscosity of the ECM by degrading the hyaluronate constituent of theses tissues (Hynes and Walton, 2000).

Autoinducer-2 and Superantigens

Biofilm formation is also dependent on hyaluronidase activity and on autoinducer-2 (AI-ii), a furanosyl borate diester signal molecule production of the luxS factor. AI-2 controls quorum-sensing communication, and, past that, the tendency for biofilm formation. S. intermedius pathogenesis is induced past biofilm formation, which also decreases antibiotic susceptibility and protects from host immunological defenses (Vendeville et al., 2005; Pecharki et al., 2008b). S. intermedius expresses additional defensive genes to oppose the human immune system, such equally superantigens that cause lymphocyte apoptosis or proteins to arrest lymphocyte and fibroblast proliferation (Arala-Chaves et al., 1979; Proft and Fraser, 1998).

The Capsule

A college tendency for abscess formation is observed in encapsulated Due south. intermedius isolates (Brook and Walker, 1985). In fact, the polysaccharidic sheathing of S. intermedius prevents phagocytosis, every bit it inhibits polymorphonuclear neutrophils from exerting a phagocytic function to allow for replication after inflow to the infection site and adherence. This inhibition depends on the concentration of capsular polysaccharides (Wessels, 1997; Kanamori et al., 2004).

Streptococcus Invasion Locus (sil)

Bacterial invasion is assisted by a complete Streptococcus Invasion locus (sil) system detected in S. intermedius (Issa et al., 2019). The sil genes improve virulence and delay wound healing in S. pyogenes infections (Salim et al., 2008). Their activity was kickoff identified in GAS members where a transposon insertion in the sil system attenuated virulence in a murine model (Hidalgo-Grass et al., 2002). Moreover, the sil system has been implicated in the regulation of microbe–microbe interactions at mucosal surfaces through putative bacteriocins that gave Southward. intermedius a competitive advantage (Mendonca et al., 2017).

Intermedilysin and Sialidase A

Two S. intermedius-specific virulence factors, namely the intermedilysin (ILY) and sialidase A (NanA), are not found in other members of the SAG grouping and are preserved nether purifying option (Takao et al., 2010; Issa et al., 2019). Cholesterol-dependent cytolysin ILY does not bind cholesterol directly, which makes South. intermedius a strictly homo-specific pathogen (Giddings et al., 2004). Instead, ILY binds its cell-surface receptor hCD59, which initiates pore circuitous formation in host cell membranes peculiarly carmine blood cells causing their programmed necrosis (Giddings et al., 2004) and prevents binding to the C8 and C9 complement components, thereby inducing host cell lysis via the formation of the membrane assail complex (MAC) (LaChapelle et al., 2009).

NanA, on the other mitt, contributes to pathogenicity by controlling inter-bacterial communication and host-bacterial interactions through releasing sialic acrid moieties from sugar chains nowadays in the environment and the surface of leaner (Long et al., 2004; Orihuela et al., 2004; Takao et al., 2010).

Regulation of Cistron Expression

ILY activity is reciprocally regulated past either activation of ily cistron expression or immunological inhibition by blood modulators according to carbohydrate availability.

Glucose-Poor Weather

In the absenteeism of glucose, the metabolic deposition of glycans in the human being serum by multi-substrate glycosidase A (MsgA) and NanA releases Northward-acetylneuraminic acid and galactose. The latter is an inhibitory monosaccharide of the lactose phosphotransferase organization repressor (LacR) (Tomoyasu et al., 2013; Imaki et al., 2014). Being a transcriptional regulator from the GntR family, LacR normally binds to the ily promoter and represses transcription (Rooijen et al., 1992; Tomoyasu et al., 2013). Therefore, inactivation of LacR nether galactose-rich weather condition results in constitutive ILY stimulation, equally seen past the increased toxicity toward hepatoma cells. MsgA and NanA expression is also upregulated by a positive feedback loop, which induces S. intermedius virulence (Tomoyasu et al., 2017). Notably, genomic assay of a deep-seated abscess correlated a non-functional and mutated LacR to ILY overproduction (Tomoyasu et al., 2013). The expression blueprint of ILY is, still, negatively affected by elevated concentrations of other utilizable sugars, including glucose, fructose, and maltose.

Glucose-Rich Conditions

Nether abundant glucose supply, transcriptional repression of ILY is achieved by the catabolite control protein (CcpA), which either binds to the ily promoter on the catabolite repressible element (cre) or controls the concentration of transcriptional regulators for ily. The dual inhibition pathways suggested the presence of two alternate sugar-dependent types of growth, rapid-slightly virulent and ho-hum-highly virulent, depending on ecology saccharide abundance or limitation, respectively (Tomoyasu et al., 2010). Sugar association with ily gene expression suggested the presence of mechanisms controlling sugar concentrations (Tomoyasu et al., 2017). Given the importance of ILY in the increased virulence of this pathogen, further work is warranted to characterize the mechanisms involved and their correlation to pathogenicity and/or commensalism.

Sugar availability is likewise important during the early on stages of infection; the ability of South. intermedius to survive dental restoration and obtain nutrients for survival has been linked to deposition of galactose, N-acetyl-D-glucosamine, and N-acetylneuraminic acid on serum glycoproteins from the pulp of the infected dentin (Paddick et al., 2005).

Oxygen Availability

Differential growth kinetics and metabolic activities of South. intermedius are influenced by oxygen availability, as observed by Fei et al. (2016). S. intermedius showed an increased growth charge per unit in an anaerobic surround, which could be prompted by an increased expression of genes interim in nucleoside and nucleotide metabolism. Furthermore, an upregulation of glycolysis-associated genes resulted in an increased glucose metabolism. An enhanced expression of the glycogen biosynthesis operon (glgABCD) was also observed, suggesting the storage of glucose in the form of glycogen (Fei et al., 2016).

Moreover, under anaerobic conditions, Southward. intermedius increased arginine turnover to carbamoyl phosphate via the arginine deiminase pathway, leading to an increase in pyrimidine de novo synthesis (Fei et al., 2016). As such, arginine consumption by S. intermedius limited nitric oxide production past host cells, favoring, as a result, its survival in the host (Stadelmann et al., 2013; Cusumano et al., 2014). Although the expression of virulence-associated genes was not related to the presence or absenteeism of oxygen, nanA and pulA genes were upregulated under anaerobic weather condition (Fei et al., 2016).

On the other paw, nether aerobic conditions, genes encoding DNA-repair pathways, atomic number 26 metabolism, and iron-sulfur clusters were upregulated (Fei et al., 2016).

Notably, bacterial membrane composition also varied to adjust the differences in oxygen availability (Fei et al., 2016). These observed changes in the membrane merit farther investigation to map their role in S. intermedius pathogenesis, if any.

Immunological Inhibition

Immunoglobulins in the human plasma also have a regulative holding in preventing ILY, MsgA, and NanA activities (Tomoyasu et al., 2017). ILY-silencing experiments via an anti-ILY antibody showed decreased S. intermedius cytotoxicity toward cancerous human liver cells (Sukeno et al., 2005). Efficiency of the immunoreaction relies on antibody concentration particularly since partial neutralization of ILY activeness in immunocompromised patients would exert a positive feedback mechanism on ily product further inducing infection rather than terminating information technology (Tomoyasu et al., 2017). Antibiotic concentration represents a form of adaptive immune machinery since higher anti-ILY levels are observed in patients with past S. intermedius infections. Human plasma immunoglobulins that neutralize ILY could too neutralize MsgA and NanA activities, though to varying extents (Tomoyasu et al., 2017).

The luxS Pathway

An additional ily and hyl level of regulation involves luxS (autoinducer-; AI-2). Mutations introduced in luxS led to a subtract in ily and hyl expression and attenuated ILY hemolytic activity, though not that of hyaluronidase. The disposition of membrane antigens I/Two didn't modify every bit luxS does non command the expression of the relevant genes (fbp54 for antigen I and lmb for antigen II) (Pecharki et al., 2008a). AI-2 mediated regulation also involves other factors, such as iron acquisition, saccharide metabolism, proteolytic and hemolytic activities, antibiotic production, and biofilm formation (Vendeville et al., 2005). The link between the luxS and regulation of carbohydrate metabolism is non still clear. The role of luxS as a 'chief factor' might suggest its involvement in the command of sugar-sensing monitors at the base of sugar-dependent regulation.

Genome Insights

The S. intermedius genome is comprised of a unmarried circular chromosome having an average size of 1.99 Mbp and includes roughly ∼1,700 coding genes and a 37.6% G + C content. Like to other streptococci (Ajdiæ et al., 2002; Holden et al., 2009), no plasmid DNA have been reported in S. intermedius (Olson et al., 2013). At least two S. constellatus strains have been previously misidentified and deposited on NCBI equally S. intermedius, F0395 (Jensen et al., 2013), and 567_SINT (Issa et al., 2019). The genome of S. intermedius consists of 1,327 cadre genes (≥ 99% of isolates), 991 shell genes nowadays in two or more than isolates (xv% ≤ isolates < 95%), and 1,672 unique cloud genes specific to single isolates (0% ≤ isolates < 15%) (Issa et al., 2019). This is less than the i,617 core genes establish in Southward. constellatus (Olson et al., 2013).

Few studies have been performed on the whole-genome molecular characterization and comparative genome analysis of S. intermedius (Olson et al., 2013; Planet et al., 2013; Hasegawa et al., 2017; Issa et al., 2019). A genome announcement for the BA1 strain isolated from an intracranial abscess in a child was published by Planet et al. (2013). Olson et al. (2013) used an intra and inter species comparative genome analysis approach of seven SAG genomes and 59 publicly available Streptococcus genomes to clarify the phylogenetic relationships of these bacteria and supports their distinct species classification. Shared orthologous proteins suggested that the SAG genomes were most closely related to S. gordonii and S. sanguinis even so harbored a similar number of proteins inside each COG category to other Streptococcus species. South. intermedius was generally like to S. constellatus. Mobile elements, primarily integrative conjugative elements, and bacteriophage were plant to account for more x% of the SAG genomes with S. anginosus beingness the most variable species. S. intermedius and Southward. constellatus, on the other manus, shared greater than half of their virulence traits and with numerous potential virulence determinants in SAG.

Hasegawa et al. (2017) performed a comprehensive molecular characterization of S. intermedius pathogenicity based on the complete genome sequence and a murine subcutaneous abscess model with transcriptome and random transposon mutagenesis of TYG1620 strain isolated from a brain abscess in an babe. They reported the presence of a notable type VII secretion organisation (T7SS), two long repeat regions, and xix ORFs for cell wall-anchored proteins (CWAPs). Transcriptome analysis in a murine subcutaneous abscess model suggested that the levels of expression of small hypothetical proteins like to phenol-soluble modulin _1 (PSM_1), a staphylococcal virulence factor, significantly increased in the abscess model. Finally, Issa et al. (2019) performed a whole-genome comparative analysis of LAU_SINT associated with a brain abscess with 16 S. intermedius genomes in addition to S. constellatus and S. anginosus. No geographical correlation between pan-genome and SNPs-based analysis could exist established. Four different T7SS modules (I–4) located on various genomic island were described, and nisin resistance determinants were institute in 47% of the isolates.

Conclusion

S. intermedius is one of the most common pathogens associated with brain as well every bit liver abscesses and thoracic empyema. A search on PubMed Fundamental revealed that SAG members are clearly underrepresented compared to other medically relevant streptococci. Patients with invasive S. intermedius infections have a significantly longer hospital stay and higher mortality rates than other SAG members. Dental manipulation or sinusitis are the ii most of import underlying risk factors for S. intermedius infections. Almost all infections are associated with abscess development, detected through diverse imaging approaches including CT, scans, and MRIs. Due south. intermedius brain abscess formation begins with tissue damage mediated past the bounden to homo fibronectin and laminin and the subsequent Il-viii release from monocytes, which activates neutrophil chemotaxis and contributes to the proinflammatory cytokine build-upwardly causing tissue damage. Due south. intermedius expresses hydrolytic enzymes responsible for the tissue liquefaction and pus formation with higher hyaluronidase concentrations existence observed in deeper abscesses. Biofilm formation is also dependent on hyaluronidase activity and on AI-two. ILY and NanA, two important virulence determinants, are not found in other members of the SAG group. ILY activity is regulated by ily gene expression and/or immunological inhibition past blood modulators depending on the availability of carbohydrates. Abscess drainage and surgery remained the just interventions to limit the abscess. A variety of antibiotics were prescribed to treat the patients with combination therapies being the dominant used approach. Upon admission, the most commonly prescribed antibody regimens were a combination of ceftriaxone and metronidazole lonely or combined with vancomycin. The prescribed antibiotic regimen was changed nearly oft to include metronidazole, ceftriaxone, or meropenem.

Sugar association with ily cistron expression and the correlation between a deep-seated abscess with a non-functional and mutated LacR warrant further studies to better narrate the mechanisms involved. Medical diagnostic laboratories could adopt ily PCR for a rapid and authentic identification and diagnosis in cases where patients nowadays whatsoever of the previously stated chance factors and symptoms. In this context, improved guidelines for antibiotics drug assistants can aid in preventing the random and excessive antibiotics usage in S. intermedius infections. Additional research is also required to elucidate mechanisms used past S. intermedius to cross the blood brain barrier and to design and implement targeted therapeutic approaches. Finally, the dependency of S. intermedius virulence on sugar availability requires further experimental testing, as it represents an alternative nutritional therapy based on dietary restriction of sugar intake.

Summary

This review aimed at summarizing our current noesis of S. intermedius, its various identification methods, known virulence factors, and regulation of gene expression involved in abscess development. Members of the SAG are role of the normal microbiota beingness found at diverse mucosal sites and are frequently encountered in invasive suppurative infections. SAG members share few common characteristics and take a variable Lancefield serogrouping. Different identification approaches were used with the nearly promising being the MLSA and WGS, with the WGS approach providing a better resolution and discriminatory power. Currently, 42 genome assemblies of South. intermedius are available on NCBI database, and S. intermedius even so remains underrepresented compared to other SAG members and other medically relevant streptococci. A total of 101 cases with available patient's metadata were retained in this review, which revealed a male predominance of S. intermedius infections with most patients showing upon access intermittent fever and consistent headaches. Blood tests for the C-reactive poly peptide and WBC count were elevated and indicative of an infection. The most important underlying risk factor and comorbidity was dental manipulation and sinusitis, respectively. Abscess drainage and surgery remained as the simply interventions to limit the abscess, and antibiotic treatment prescribed upon hospital access was most frequently changed to include metronidazole, which was the most commonly prescribed antibody. The onset of S. intermedius encephalon abscess germination first begins with tissue damage that precedes bacterial colonization, tissue liquefaction, and pus formation through hyaluronidase activeness. Several virulence factors were detected, and ILY and NanA were specific to Due south. intermedius. Carbohydrate association with ily gene expression and the correlation betwixt deep-seated abscess with a not-functional and mutated LacR warrant further studies to better narrate the mechanisms involved. Moreover, ily based PCR identification and improved guidelines for drug administration could assistance in preventing the random and excessive antibiotics usage in treating Due south. intermedius infections. Additional enquiry is as well required to elucidate the mechanisms used past Southward. intermedius to cross the blood brain bulwark and to make up one's mind the correlation between virulence and carbohydrate availability.

Writer Contributions

ST performed the study conceptualization and performed the supervision. EI and TS performed the literature search, performed the writing, and the original draft preparation. ST, EI, and TS carried out the critical discussion, carried out the writing, reviewing, and editing. All authors have read and agreed to the published version of the manuscript.

Conflict of Involvement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Supplementary Material

The Supplementary Cloth for this commodity can be establish online at: https://world wide web.frontiersin.org/articles/x.3389/fmicb.2020.00826/full#supplementary-material

Footnotes

1. ^ http://www.eMLSA.cyberspace

References

Ahmed, R. A., Marrie, T. J., and Huang, J. Q. (2006). Thoracic empyema in patients with community-Caused Pneumonia. Am. J. Med. 119, 877–883. doi: x.1016/j.amjmed.2006.03.042

CrossRef Full Text | Google Scholar

Ajdiæ, D., McShan, West. Chiliad., McLaughlin, R. E., Saviæ, G., Chang, J., Carson, M. B., et al. (2002). Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc. Natl. Acad. Sci. U.Southward.A. 99, 14434–14439. doi: 10.1073/pnas.172501299

CrossRef Full Text | Google Scholar

Anderton, J. Thousand., Rajam, One thousand., Romero-Steiner, S., Summer, S., Kowalczyk, A. P., Carlone, 1000. M., et al. (2007). Eastward-cadherin is a receptor for the common protein pneumococcal surface adhesin A (PsaA) of Streptococcus pneumoniae. Microb. Pathog. 42, 225–236.

Google Scholar

Arala-Chaves, M. P., Higerd, T. B., Porto, K. T., Munoz, J., Goust, J. Grand., Fudenberg, H. H., et al. (1979). Evidence for the synthesis and release of strongly immunosuppressive, noncytotoxic substances by Streptococcus intermedius. J. Clin. Invest. 64, 871–883. doi: x.1172/JCI109553

CrossRef Full Text | Google Scholar

Baddour, L. One thousand. (1994). Virulence factors among gram-positive bacteria in experimental endocarditis. Infect. Immun. 62, 2143–2148.

Google Scholar

Bantar, C., Canigia, L. F., Relloso, South., Lanza, A., Bianchini, H., and Smayevsky, J. (1996). Species belonging to the "Streptococcus milleri" group: antimicrobial susceptibility and comparative prevalence in significant clinical specimens. J. Clin. Microbiol. 34, 2020–2022.

Google Scholar

Bishop, C. J., Aanensen, D. Chiliad., Jordan, Grand. E., Kilian, M., Hanage, W. P., and Spratt, B. G. (2009). Assigning strains to bacterial species via the internet. BMC Biol. 7:iii. doi: x.1186/1741-7007-7-3

CrossRef Full Text | Google Scholar

Brook, I., and Walker, R. I. (1985). The role of encapsulation in the pathogenesis of anaerobic gram-positive cocci. Can. J. Microbiol. 31, 176–180. doi: x.1139/m85-033

CrossRef Full Text | Google Scholar

Brouwer, Chiliad. C., Coutinho, J. One thousand., and van de Beek, D. (2014). Clinical characteristics and outcome of brain abscess: systematic review and meta-analysis. Neurology 82, 806–813. doi: 10.1212/WNL.0000000000000172

CrossRef Full Text | Google Scholar

Casariego, E., Rodriguez, A., Corredoira, J. C., Alonso, P., Coira, A., Bal, 1000., et al. (1996). Prospective written report of Streptococcus milleri bacteremia. Eur. J. Clin. Microbiol. Infect. Dis. fifteen, 194–200. doi: 10.1007/BF01591353

CrossRef Total Text | Google Scholar

Clarridge, J. E., Attorri, Southward., Musher, D. Thousand., Hebert, J., and Dunbar, South. (2001). Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus ("Streptococcus milleri Group") are of different clinical importance and are not equally associated with abscess. Clin. Infect. Dis. 32, 1511–1515. doi: x.1086/320163

CrossRef Full Text | Google Scholar

Coykendall, A. L., Wesbecher, P. M., and Gustafson, M. B. (1987). Streptococcus milleri" Streptococcus constellatus, and Streptococcus intermedius Are Subsequently Synonyms of Streptococcus anginosus. Int. J. Syst. Evol. Microbiol. 37, 222–228. doi: 10.1099/00207713-37-3-222

CrossRef Total Text | Google Scholar

Cusumano, Z. T., Watson, K. Due east., and Caparon, M. G. (2014). Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity. Infect. Immun. 82, 233–242.

Google Scholar

Desar, I. One thousand. E., de Boer, Thousand., Bens, C. C. P. Grand., Jacobs, J. A., Mouton, J. Due west., Dofferhoff, A. S. Thou., et al. (2008). Rapid and reliable identification of Streptococcus anginosus grouping isolates to the species level by existent-time PCR and melting curve analysis. J. Microbiol. Methods 75, 372–374. doi: 10.1016/j.mimet.2008.06.022

CrossRef Total Text | Google Scholar

Facklam, R. (2002). What happened to the Streptococci: overview of taxonomic and classification changes. Clin. Microbiol. Rev. 15, 613–630. doi: 10.1128/CMR.15.4.613-630.2002

CrossRef Total Text | Google Scholar

Fei, F., Mendonca, Thousand. L., McCarry, B. E., Bowdish, D. M. E., and Surette, G. One thousand. (2016). Metabolic and transcriptomic profiling of Streptococcus intermedius during aerobic and anaerobic growth. Metabolomics 12:46. doi: x.1007/s11306-016-0966-0

CrossRef Total Text | Google Scholar

Friedrichs, C., Rodloff, A. C., Chhatwal, G. S., Schellenberger, West., and Eschrich, M. (2007). Rapid identification of viridans Streptococci by mass spectrometric bigotry. J. Clin. Microbiol. 45, 2392–2397. doi: 10.1128/JCM.00556-07

CrossRef Full Text | Google Scholar

Furuichi, 1000., and Horikoshi, Y. (2018). Sites of infection associated with Streptococcus anginosus grouping among children. J. Infect. Chemother. 24, 99–102. doi: 10.1016/j.jiac.2017.09.011

CrossRef Full Text | Google Scholar

Ge, J., Catt, D. M., and Gregory, R. Fifty. (2004). Streptococcus mutans surface α-enolase binds salivary mucin MG2 and man plasminogen. Infect. Immun. 72, 6748–6752.

Google Scholar

Giddings, Thou. S., Zhao, J., Sims, P. J., and Tweten, R. K. (2004). Man CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin. Nat. Struct. Mol. Biol. 11, 1173–1178. doi: 10.1038/nsmb862

CrossRef Full Text | Google Scholar

Gossling, J. (1988). Occurrence and pathogenicity of the Streptococcus milleri grouping. Rev. Infect. Dis. 10, 257–285. doi: 10.1093/clinids/ten.ii.257

CrossRef Full Text | Google Scholar

Goto, T., Nagamune, H., Miyazaki, A., Kawamura, Y., Ohnishi, O., Hattori, K., et al. (2002). Rapid identification of Streptococcus intermedius past PCR with the ily gene as a species mark cistron. J. Med. Microbiol. 51, 178–186.

Google Scholar

Grinwis, Chiliad. E., Sibley, C. D., Parkins, M. D., Eshaghurshan, C. South., Rabin, H. R., and Surette, Thousand. G. (2010). Characterization of Streptococcus milleri group isolates from expectorated sputum of adult patients with cystic fibrosis. J. Clin. Microbiol. 48, 395–401. doi: 10.1128/JCM.01807-09

CrossRef Full Text | Google Scholar

Hasegawa, Northward., Sekizuka, T., Sugi, Y., Kawakami, N., Ogasawara, Y., Kato, Thousand., et al. (2017). Characterization of the Pathogenicity of Streptococcus intermedius TYG1620 isolated from a human being encephalon abscess based on the consummate genome sequence with transcriptome analysis and transposon mutagenesis in a murine subcutaneous abscess model. Infect. Immun. 85:e00886-xvi. doi: x.1128/IAI.00886-sixteen

CrossRef Full Text | Google Scholar

Hidalgo-Grass, C., Ravins, 1000., Dan-Goor, Thou., Jaffe, J., Moses, A. Due east., and Hanski, E. (2002). A locus of grouping A Streptococcus involved in invasive disease and DNA transfer. Mol. Microbiol. 46, 87–99.

Google Scholar

Holden, M. T. G., Hauser, H., Sanders, M., Ngo, T. H., Cherevach, I., Cronin, A., et al. (2009). Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis. PLoS Ane 4:e6072. doi: 10.1371/periodical.pone.0006072

CrossRef Full Text | Google Scholar

Homer, K., Shain, H., and Beighton, D. (1997). "The function of hyaluronidase in growth of Streptococcus intermedius on hyaluronate," in Streptococci and the Host, eds T. Horaud and Thousand. Sicard (Berlin: Springer), 681–683.

Google Scholar

Hynes, Due west. L., and Walton, S. L. (2000). Hyaluronidases of Gram-positive bacteria. FEMS Microbiol. Lett. 183, 201–207. doi: ten.1111/j.1574-6968.2000.tb08958.10

CrossRef Full Text | Google Scholar

Hytönen, J., Haataja, Due south., and Finne, J. (2003). Streptococcus pyogenes glycoprotein-binding strepadhesin activity is mediated past a surface-associated sugar-degrading enzyme, pullulanase. Infect. Immun. 71, 784–793.

Google Scholar

Imaki, H., Tomoyasu, T., Yamamoto, Northward., Taue, C., Masuda, S., Takao, A., et al. (2014). Identification and characterization of a novel secreted glycosidase with multiple glycosidase activities in Streptococcus intermedius. J. Bacteriol. 196, 2817–2826. doi: 10.1128/JB.01727-14

CrossRef Total Text | Google Scholar

Issa, E., Salloum, T., Panossian, B., Ayoub, D., Abboud, East., and Tokajian, S. (2019). Genome Mining and Comparative Assay of Streptococcus intermedius Causing Brain Abscess in a Kid. Pathogens 8:22. doi: 10.3390/pathogens8010022

CrossRef Total Text | Google Scholar

Jacobs, J. A., Pietersen, H. G., Stobberingh, Due east. E., and Soeters, P. B. (1994). Bacteremia Involving the "Streptococcus milleri" group: assay of nineteen Cases. Clin. Infect. Dis. nineteen, 704–713. doi: 10.1093/clinids/nineteen.iv.704

CrossRef Full Text | Google Scholar

Jacobs, J. A., Pietersen, H. Thousand., Stobberingh, E. E., and Soeters, P. B. (1995). Streptococcus anginosus, Streptococcus constellatus and Streptococcus intermedius clinical relevance, hemolytic and serologic characteristics. Am. J. Clin. Pathol. 104, 547–553. doi: x.1093/ajcp/104.v.547

CrossRef Total Text | Google Scholar

Jensen, A., Hoshino, T., and Kilian, Grand. (2013). Taxonomy of the Anginosus grouping of the genus Streptococcus and description of Streptococcus anginosus subsp. whileyi subsp. november. and Streptococcus constellatus subsp. viborgensis subsp. november. Int. J. Syst. Evol. Microbiol. 63, 2506–2519. doi: ten.1099/ijs.0.043232-0

CrossRef Full Text | Google Scholar

Jones, D. (1978). Limerick and differentiation of the genus Streptococcus. Soc. Appl. Bacteriol. Symp. Ser. 7, 1–49.

Google Scholar

Junckerstorff, R. K., Robinson, J. O., and Murray, R. J. (2014). Invasive Streptococcus anginosus group infection—does the species predict the consequence? Int. J. Infect. Dis. 18, 38–xl. doi: 10.1016/j.ijid.2013.09.003

CrossRef Total Text | Google Scholar

Kanamori, S., Shinzato, T., Saito, A., and Kusano, Northward. (2004). The role of the capsule of the Streptococcus milleri grouping in its pathogenicity. J. Infect. Chemother. 10, 105–109. doi: 10.1007/s10156-004-0305-7

CrossRef Full Text | Google Scholar

Kielian, T., Barry, B., and Hickey, West. F. (2001). CXC Chemokine Receptor-ii Ligands Are required for Neutrophil-Mediated host defence in experimental brain abscesses1. J. Immunol. 166, 4634–4643. doi: 10.4049/jimmunol.166.7.4634

CrossRef Full Text | Google Scholar

Kilian, M., Mikkelsen, L., and Henrichsen, J. (1989). Taxonomic Report of Viridans Streptococci: clarification of Streptococcus gordonii sp. nov. and emended descriptions of Streptococcus sanguis (White and Niven 1946), Streptococcus oralis (Bridge and Sneath 1982), and Streptococcus mitis (Andrewes and Horder 1906). Int. J. Syst. Evol. Microbiol. 39, 471–484. doi: 10.1099/00207713-39-4-471

CrossRef Full Text | Google Scholar

Kobo, O., Nikola, S., Geffen, Y., and Paul, M. (2017). The pyogenic potential of the unlike Streptococcus anginosus group bacterial species: retrospective cohort study. Epidemiol. Infect. 145, 3065–3069. doi: 10.1017/S0950268817001807

CrossRef Full Text | Google Scholar

LaChapelle, S., Tweten, R. K., and Hotze, E. M. (2009). Intermedilysin-Receptor Interactions during Assembly of the Pore Circuitous assembly intermediates increment host cell susceptibility to complement-mediated lysis. J. Biol. Chem. 284, 12719–12726. doi: x.1074/jbc.M900772200

CrossRef Total Text | Google Scholar

Liu, D., Yumoto, H., Hirota, Thou., Murakami, K., Takahashi, K., Hirao, G., et al. (2008). Histone-like Dna binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways. Cell Microbiol. 10, 262–276. doi: 10.1111/j.1462-5822.2007.01040.x

CrossRef Full Text | Google Scholar

Livingston, Fifty. Five., and Perez-Colon, East. (2014). Streptococcus intermedius bacteremia and liver abscess following a routine dental cleaning. Example Rep. Infect. Dis. 2014:954046. doi: x.1155/2014/954046

CrossRef Total Text | Google Scholar

Long, J. P., Tong, H. H., and DeMaria, T. F. (2004). Immunization with Native or Recombinant Streptococcus pneumoniae neuraminidase affords protection in the Chinchilla otitis media model. Infect. Immun. 72, 4309–4313. doi: 10.1128/IAI.72.7.4309-4313.2004

CrossRef Total Text | Google Scholar

De Louvois, J., Brownish, Due east. Thousand., Bayston, R., and Lees, P. D. (2000). The rational utilize of antibiotics in the treatment of brain abscess. Br. J. Neurosurg. 14, 525–530. doi: 10.1080/02688690020005527

CrossRef Total Text | Google Scholar

Mendonca, G. L., Szamosi, J. C., Lacroix, A.-M., Fontes, M. E., Bowdish, D. Thousand., and Surette, M. Chiliad. (2017). The sil locus in Streptococcus anginosus group: interspecies competition and a hotspot of genetic diversity. Front. Microbiol. 7:2156. doi: 10.3389/fmicb.2016.02156

CrossRef Full Text | Google Scholar

Mohammadi, F., Khademi, Grand., Afzalaghaee, 1000., and Sasan, M. South. (2019). The Result of antibody stewardship targeted against vancomycin and carbapenems on antibody usage in PICU. Int. J. Med. Sci. Clin. Invent. half dozen, 4308–4312. doi: 10.18535/ijmsci/v6i2.05

CrossRef Full Text | Google Scholar

Olson, A. B., Kent, H., Sibley, C. D., Grinwis, Yard. Eastward., Mabon, P., Ouellette, C., et al. (2013). Phylogenetic relationship and virulence inference of Streptococcus anginosus Group: curated notation and whole-genome comparative analysis support singled-out species designation. BMC Genomics 14:895. doi: 10.1186/1471-2164-14-895

CrossRef Total Text | Google Scholar

Olson, A. B., Sibley, C. D., Schmidt, L., Wilcox, M. A., Surette, M. G., and Corbett, C. R. (2010). Development of Real-Time PCR assays for detection of the Streptococcus milleri group from cystic fibrosis clinical specimens by targeting the cpn60 and 16S rRNA Genes. J. Clin. Microbiol. 48, 1150–1160. doi: 10.1128/JCM.02082-09

CrossRef Full Text | Google Scholar

Orihuela, C. J., Gao, Thou., Francis, G. P., Yu, J., and Tuomanen, E. I. (2004). Tissue-Specific contributions of pneumococcal virulence factors to pathogenesis. J. Infect. Dis. 190, 1661–1669. doi: 10.1086/424596

CrossRef Total Text | Google Scholar

Paddick, J. Southward., Brailsford, S. R., Kidd, Eastward. A. M., and Beighton, D. (2005). Phenotypic and genotypic selection of microbiota surviving under dental restorations. Appl. Environ. Microbiol. 71, 2467–2472. doi: 10.1128/AEM.71.5.2467-2472.2005

CrossRef Full Text | Google Scholar

Parkins, Grand. D., Sibley, C. D., Surette, M. Chiliad., and Rabin, H. R. (2008). The Streptococcus milleri group—An unrecognized cause of disease in cystic fibrosis: a example serial and literature review. Pediatr. Pulmonol. 43, 490–497. doi: ten.1002/ppul.20809

CrossRef Full Text | Google Scholar

Pecharki, D., Petersen, F. C., and Scheie, A. A. (2008a). LuxS and expression of virulence factors in Streptococcus intermedius. Oral Microbiol. Immunol. 23, 79–83. doi: ten.1111/j.1399-302X.2007.00395.ten

CrossRef Full Text | Google Scholar

Pecharki, D., Petersen, F. C., and Scheie, A. A. (2008b). Part of hyaluronidase in Streptococcus intermedius biofilm. Microbiology 154, 932–938. doi: 10.1099/mic.0.2007/012393-0

CrossRef Total Text | Google Scholar

Petersen, F. C., Pasco, S., Ogier, J., Klein, J. P., Assev, S., and Scheie, A. A. (2001). Expression and Functional Properties of theStreptococcus intermedius Surface Protein Antigen I/II. Infect. Immun. 69, 4647–4653. doi: 10.1128/IAI.69.7.4647-4653.2001

CrossRef Total Text | Google Scholar

Planet, P. J., Rampersaud, R., Hymes, S. R., Whittier, S., Della-Latta, P. A., Narechania, A., et al. (2013). Genome sequence of the human abscess isolate Streptococcus intermedius BA1. Genome Announc. one:e00117-12. doi: x.1128/genomeA.00117-12

CrossRef Full Text | Google Scholar

Prasad, K. N., Mishra, A. M., Gupta, D., Husain, N., Husain, Grand., and Gupta, R. K. (2006). Analysis of microbial etiology and bloodshed in patients with brain abscess. J. Infect. 53, 221–227. doi: 10.1016/j.jinf.2005.12.002

CrossRef Total Text | Google Scholar

Proft, T., and Fraser, J. (1998). Superantigens: but similar peptides but different. J. Exp. Med. 187, 819–821.

Google Scholar

Reißmann, S., Friedrichs, C., Rajkumari, R., Itzek, A., Fulde, G., Rodloff, A. C., et al. (2010). Contribution of Streptococcus anginosus to infections caused by groups C and G Streptococci, Southern India. Emerg. Infect. Dis. 16, 656–663. doi: 10.3201/eid1604.090448

CrossRef Full Text | Google Scholar

Rooijen, R. J., van, Gasson, M. J., and de Vos, Due west. M. (1992). Characterization of the Lactococcus lactis lactose operon promoter: contribution of flanking sequences and LacR repressor to promoter activity. J. Bacteriol. 174, 2273–2280. doi: 10.1128/jb.174.7.2273-2280.1992

CrossRef Full Text | Google Scholar

Ruoff, K. L., and Ferraro, Thousand. J. (1987). Hydrolytic enzymes of "Streptococcus milleri". J. Clin. Microbiol. 25, 1645–1647.

Google Scholar

Salim, K. Y., De Azavedo, J. C., Bast, D. J., and Cvitkovitch, D. G. (2008). Regulation of sagA, siaA and scpC by SilCR, a putative signaling peptide of Streptococcus pyogenes. FEMS Microbiol. Lett. 289, 119–125. doi: 10.1111/j.1574-6968.2008.01375.x

CrossRef Full Text | Google Scholar

Schouls, Fifty. M., Schot, C. Due south., and Jacobs, J. A. (2003). Horizontal transfer of segments of the 16S rRNA Genes between Species of the Streptococcus anginosus group. J. Bacteriol. 185, 7241–7246. doi: 10.1128/JB.185.24.7241-7246.2003

CrossRef Total Text | Google Scholar

Sibley, C. D., Church building, D. L., Surette, Yard. Chiliad., Dowd, S. E., and Parkins, M. D. (2012). Pyrosequencing reveals the complex polymicrobial nature of invasive pyogenic infections: microbial constituents of empyema, liver abscess, and intracerebral abscess. Eur. J. Clin. Microbiol. Infect. Dis. 31, 2679–2691. doi: 10.1007/s10096-012-1614-x

CrossRef Total Text | Google Scholar

Sibley, C. D., Grinwis, M. East., Field, T. R., Parkins, Grand. D., Norgaard, J. C., Gregson, D. B., et al. (2010). McKay agar enables routine quantification of the 'Streptococcus milleri' group in cystic fibrosis patients. J. Med. Microbiol. 59, 534–540. doi: 10.1099/jmm.0.016592-0

CrossRef Full Text | Google Scholar

Siegman-Igra, Y., Azmon, Y., and Schwartz, D. (2012). Milleri grouping streptococcus—a stepchild in the viridans family. Eur. J. Clin. Microbiol. Infect. Dis. 31, 2453–2459. doi: 10.1007/s10096-012-1589-7

CrossRef Total Text | Google Scholar

Stadelmann, B., Hanevik, Chiliad., Andersson, Thou. K., Bruserud, O., and Svärd, Southward. G. (2013). The role of arginine and arginine-metabolizing enzymes during Giardia–host cell interactions in vitro. BMC Microbiol. 13:256. doi: ten.1186/1471-2180-xiii-256

CrossRef Full Text | Google Scholar

Sukeno, A., Nagamune, H., Whiley, R. A., Jafar, Due south. I, Aduse-Opoku, J., Ohkura, K., et al. (2005). Intermedilysin is essential for the invasion of Hepatoma HepG2 Cells by Streptococcus intermedius. Microbiol. Immunol. 49, 681–694. doi: 10.1111/j.1348-0421.2005.tb03647.x

CrossRef Total Text | Google Scholar

Suzuki, H., Hase, R., Otsuka, Y., and Hosokawa, N. (2016). Bloodstream infections acquired by Streptococcus anginosus group bacteria: a retrospective analysis of 78 cases at a Japanese third infirmary. J. Infect. Chemother. 22, 456–460. doi: 10.1016/j.jiac.2016.03.017

CrossRef Full Text | Google Scholar

Takao, A., Nagamune, H., and Maeda, North. (2004). Identification of the anginosus group within the genus Streptococcus using polymerase chain reaction. FEMS Microbiol. Lett. 233, 83–89. doi: ten.1016/j.femsle.2004.01.042

CrossRef Full Text | Google Scholar

Takao, A., Nagamune, H., and Maeda, Northward. (2010). Sialidase of Streptococcus intermedius: a putative virulence factor modifying sugar bondage. Microbiol. Immunol. 54, 584–595. doi: 10.1111/j.1348-0421.2010.00257.x

CrossRef Total Text | Google Scholar

Takao, A., Nagashima, H., Usui, H., Sasaki, F., Maeda, N., Ishibashi, K., et al. (1997). Hyaluronidase activity in homo pus from which Streptococcus intermedius was isolated. Microbiol. Immunol. 41, 795–798. doi: 10.1111/j.1348-0421.1997.tb01929.x

CrossRef Full Text | Google Scholar

Tomoyasu, T., Imaki, H., Masuda, S., Okamoto, A., Kim, H., Waite, R. D., et al. (2013). LacR mutations are ofttimes observed in Streptococcus intermedius and are responsible for increased intermedilysin production and virulence. Infect. Immun. 81, 3276–3286. doi: 10.1128/IAI.00638-13

CrossRef Full Text | Google Scholar

Tomoyasu, T., Tabata, A., Hiroshima, R., Imaki, H., Masuda, S., Whiley, R. A., et al. (2010). Role of catabolite control protein a in the regulation of intermedilysin production by Streptococcus intermedius. Infect. Immun. 78, 4012–4021. doi: 10.1128/IAI.00113-ten

CrossRef Full Text | Google Scholar

Tomoyasu, T., Yamasaki, T., Chiba, South., Kusaka, S., Tabata, A., Whiley, R. A., et al. (2017). Positive- and negative-control pathways by blood components for intermedilysin production in Streptococcus intermedius. Infect. Immun. 85:e00379-17. doi: 10.1128/IAI.00379-17

CrossRef Full Text | Google Scholar

Vendeville, A., Winzer, K., Heurlier, K., Tang, C. M., and Hardie, Yard. R. (2005). Making "sense" of metabolism: autoinducer-2, LUXS and pathogenic bacteria. Nat. Rev. Microbiol. 3, 383–396. doi: x.1038/nrmicro1146

CrossRef Full Text | Google Scholar

Wessels, Chiliad. R. (1997). Biological science of streptococcal capsular polysaccharides. J. Appl. Microbiol. 83, 20S–31S. doi: ten.1046/j.1365-2672.83.s1.3.x

CrossRef Total Text | Google Scholar

Whiley, R. A., Beighton, D., Winstanley, T. K., Fraser, H. Y., and Hardie, J. Chiliad. (1992). Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus (the Streptococcus milleri grouping): association with different body sites and clinical infections. J. Clin. Microbiol. 30, 243–244.

Google Scholar

Whiley, R. A., Fraser, H., Hardie, J. Chiliad., and Beighton, D. (1990). Phenotypic differentiation of Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus strains within the "Streptococcus milleri group". J. Clin. Microbiol. 28, 1497–1501.

Google Scholar

Whiley, R. A., Hall, 50. K. C., Hardie, J. 1000., and Beighton, D. (1999). A study of modest-colony, β-haemolytic, Lancefield group C Streptococci inside the anginosus group: description of Streptococcus constellatus subsp. pharyngis subsp. november., associated with the human throat and pharyngitis. Int. J. Syst. Evol. Microbiol. 49, 1443–1449. doi: x.1099/00207713-49-four-1443

CrossRef Full Text | Google Scholar

Willcox, Yard. D. P., Patrikakis, M., and Knox, G. Due west. (1995). Degradative enzymes of oral streptococci. Aust. Dent. J. 40, 121–128. doi: x.1111/j.1834-7819.1995.tb03127.ten

CrossRef Full Text | Google Scholar

Yakut, Due north., Kadayifci, Due east. K., Karaaslan, A., Atici, Due south., Akkoc, G., Ocal Demir, South., et al. (2015). Braın abscess due to Streptococcus intermedius secondary to mastoiditis in a kid. SpringerPlus 4:809. doi: 10.1186/s40064-015-1608-0

CrossRef Full Text | Google Scholar

Source: https://www.frontiersin.org/articles/10.3389/fmicb.2020.00826/full

Posted by: sullivanwhinged.blogspot.com

Share this post