Streptococcus Dysgalactiae Subsp. Equisimilis Research Articles

Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

Streptococcal Toxic Shock Syndrome due to Streptococcus dysgalactiae subsp. equisimilis from Retroperitoneal Panniculitis during the treatment with anti-IL-6 receptor antibody: A Case Report.

A 53-year-old man with adult-onset Still's disease developed severe streptococcal toxic shock syndrome (STSS) due to Streptococcus dysgalactiae subsp. equisimilis (SDSE), following retroperitoneal panniculitis. He was receiving tocilizumab (TCZ), an interleukin-6 receptor inhibitor. The modifying effect of TCZ on the immune response and the pathophysiology of SDSE infection may have led to retroperitoneal panniculitis and atypical STSS with delayed shock and flare of soft tissue inflammation.

Effect of directive laboratory comments on prescribing response to positive throat swab cultures.

In patients without ethnicity risk factors for acute rheumatic fever (ARF), our local guidelines recommend limiting antibiotic use following a positive throat swab culture (TSC). If symptoms are severe, a 5-7 day course is recommended. Despite this, most local patients with a positive TSC for group A Streptococcus (GAS) or Streptococcus dysgalactiae subsp. equisimilis (SDSE) were being prescribed 10 days of antibiotics. In response, we added comments to positive TSC reports recommending shorter treatment durations in those without ARF risk factors. No other antimicrobial stewardship initiatives were implemented. To assess the effect of these comments on antibiotic course duration after positive TSC. All community TSC results from 1 October 2021 to 31 March 2023 (1 year pre- to 6 months post-change) were matched to antibiotic dispensing data. Patients who had been empirically dispensed an antibiotic prior to the culture report were excluded. The outcome of interest was the antibiotic duration dispensed in the 5 day period after the TSC report. Following introduction of the comments, median course duration reduced from 10 (IQR 5-10) to 7 days (IQR 0-10; P < 0.01) and from 7 (IQR 0-10) to 0 days (IQR 0-5; P < 0.01) following GAS- and SDSE-positive TSC, respectively, in those without ARF risk factors. The percentage of people receiving 10 days of antibiotics decreased from 63.0% to 37.0% (P < 0.01) and 41.2% to 14.6% (P < 0.01) for GAS and SDSE, respectively. The introduction of comments providing direct prescribing advice to requestors appears to have been highly effective at improving guideline-compliant prescribing following positive TSC report.

Streptococcus pyogenes carriage acquisition, persistence and transmission dynamics within households in The Gambia (SpyCATS): protocol for a longitudinal household cohort study.

Streptococcus pyogenes (StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC. StrepA can also asymptomatically colonise normal skin and the pharynx (carriage), potentially increasing infection risk. Streptococcus dysgalactiae subsp. equisimilis (SDSE) carriage is also common in LMIC and may interact with StrepA. This study aims to investigate StrepA and SDSE carriage and infection epidemiology, transmission dynamics and naturally acquired immunity within households in The Gambia. A longitudinal household observational cohort study will be conducted over one year. 45 households will be recruited from the urban area of Sukuta, The Gambia, resulting in approximately 450 participants. Households will be visited monthly, and available participants will undergo oropharyngeal and normal skin swabbing. Incident cases of pharyngitis and pyoderma will be captured via active case reporting, with swabs taken from disease sites. Swabs will be cultured for the presence of group A, C and G beta-haemolytic streptococci. Isolates will undergo whole genome sequencing. At each visit, clinical, socio-demographic and social mixing data will be collected. Blood serum will be collected at baseline and final visit. Oral fluid and dried blood spot samples will be collected at each visit. Mucosal and serum anti-StrepA antibody responses will be measured. This study will report StrepA and SDSE clinical epidemiology, risk factors, transmission dynamics, and serological responses to carriage and infection. Detailed social mixing behaviour will be combined with phylogenetic relatedness to model the extent of transmission occurring withing and between households. The study will provide data to help meet global strategic StrepA research goals.

Characterization of a prophage and a defective integrative conjugative element carrying the optrA gene in linezolid-resistant Streptococcus dysgalactiae subsp. equisimilis isolates from pigs, Italy.

To investigate the optrA-carrying genetic elements and their transferability in two linezolid-resistant Streptococcus dysgalactiae subsp. equisimilis (SDSE) strains of swine origin. SDSE strains (V220 and V1524) were phenotypically and genotypically characterized. Transferability of oxazolidinone resistance genes (filter mating), genetic elements and relatedness between isolates (WGS) were analysed. Excision of the genetic elements was assayed by inverse PCR. SDSE isolates were resistant to chloramphenicol, florfenicol and linezolid, but susceptible to tedizolid and both carried the optrA gene.In SDSE V220 optrA was located on a 72.9-kb ICESdyV220 inserted in the 3' end of the chromosomal rum gene. It was 94%-96% identical (coverage, from 31% to 61%) to other optrA-carrying ICEs. In-depth ICESdyV220 sequence analysis revealed that optrA was carried by an IMESdyV220 (17.9 kb), also containing the tet(O/W/32/O) gene. Inverse PCR assays excluded the ICESdyV220 mobility. In SDSE V1524, optrA was carried by the ΦSdyV1524 prophage, integrated near the 5' end of the chromosomal had gene, showing a genetic organization similar to that of other streptococcal phage. Conjugation and transduction assays failed to demonstrate the optrA transferability to streptococcal recipients. V220 and V1524 belonged to two novel sequence types (ST704 and ST634, respectively). To the best of our knowledge, this is the first identification of the optrA gene on a prophage and an ICE in SDSE isolates from swine brain.These findings are consistent with the current belief in the key role of bacteriophages and ICEs in the streptococcal evolution and adaptation.

Biofilm Production Ability of Streptococcus dysgalactiae Subsp. equisimilis: Associations with Host Species, Lancefield Group, Source, Clonal Complex, and Virulence-Associated Genes.

We assessed the biofilm production ability (BPA) of noninvasive Streptococcus dysgalactiae subsp. equisimilis (SDSE) in humans and companion animals and determined the relationship between bacterial populations with BPA and other host and microbiological features. Sixty-four isolates from companion animals and humans were collected along with host information. We measured BPA using crystal violet staining, in addition to emm typing, multilocus sequence typing, antimicrobial resistance (AMR) phenotyping/genotyping, and virulence-associated gene (VAG) detecting (prtF1-prtF2-lmb-cbp-sicG-srtp1-srtp2-brpA). Differences in the BPA of SDSE from different hosts and sources and different Lancefield groups were assessed. We analyzed the associations between populations with and without BPA (strong, moderate, weak, and no biofilm producers) and emm types, sequence types/clonal complexes (CCs), AMR phenotypes/genotypes, and VAG types. Seventeen, twenty-four, and twelve isolates were strong, moderate, and weak biofilm producers, respectively; eleven showed no BPA. There was a difference in the distribution of populations with BPA between human and animal origins and between isolates of groups G and C. We found an association between populations with BPA and the eye and ear source (vs. the pus and skin source). A relationship was observed between the populations with BPA and CC127 (vs. CC17). We observed no association between the populations with BPA and AMR phenotype/genotype. There was an association between the distribution of populations with BPA and srtp1 expression. Our observations suggest potential associations between populations with BPA and the host species, Lancefield group, source, CC, and VAG type.

A New Integrative and Mobilizable Element Is a Major Contributor to Tetracycline Resistance in Streptococcus dysgalactiae subsp. equisimilis

Tetracycline resistance in streptococci is mainly due to ribosomal protection mediated by the tet(M) gene that is usually located in the integrative and conjugative elements (ICEs) of the Tn916-family. In this study, we analyzed the genes involved in tetracycline resistance and the associated mobile genetic elements (MGEs) in Streptococcus dysgalactiae subsp. equisimilis (SDSE) causing invasive disease. SDSE resistant to tetracycline collected from 2012 to 2019 in a single hospital and from 2018 in three other hospitals were analyzed by whole genome sequencing. Out of a total of 84 SDSE isolates, 24 (28.5%) were resistant to tetracycline due to the presence of tet(M) (n = 22), tet(W) (n = 1), or tet(L) plus tet(W) (n = 1). The tet(M) genes were found in the ICEs of the Tn916-family (n = 10) and in a new integrative and mobilizable element (IME; n = 12). Phylogenetic analysis showed a higher genetic diversity among the strains carrying Tn916 than those having the new IME, which were closely related, and all belonged to CC15. In conclusion, tetracycline resistance in SDSE is mostly due to the tet(M) gene associated with ICEs belonging to the Tn916-family and a new IME. This new IME is a major cause of tetracycline resistance in invasive Streptococcus dysgalactiae subsp. equisimilis in our settings.

Identification of Novel Mobile Genetic Elements Associated with Resistance to Macrolide and Lincosamide in Streptococcus dysgalactiae subsp. equisimilis

Background: Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an important human pathogen. Recently, several studies have described the incidence of antibiotic resistance for SDSE worldwide, however, the data on the presence of corresponding genes and their possible association with mobile genetic elements are still limited. Objective: The objective of this research was to analyze the macrolide resistance in SDSE and to identify genetic determinants, mechanisms of resistance, and association with mobile genetic elements. Methods: A total of 9 SDSE strains from the collection of Joint Russian-Vietnamese Tropical Research and Technological Center (Hanoi, Vietnam) were used. These strains were previously isolated from throat swabs of children with pharyngotonsillitis in 6 provinces in Vietnam from 2012 to 2015. Antimicrobial resistance was tested by disk diffusion method. The presence of antibiotic resistance genes (ARG) was analyzed by PCR. The strains were characterized by emm typing and multilocus sequence typing (MLST). Illumina sequencing was employed for genome analysis of 4 representative SDSE isolates. Analysis of genetic elements with antibiotic resistance determinants was done using PubMed database and BLAST-searches. Artemis was used for comparative analysis of genetic elements. Results: In our study, we identified emm types that were similar to those reported in other studies. All SDSE isolates remained susceptible to penicillin, but presented alarming level of resistance to macrolides, tetracyclines, and fluoroquinolones. Most of the erythromycin-resistant strains were also characterized by clindamycin-resistance (MLSB phenotype). Both erm and different alleles of mef genes widely distributed among streptococcus pyogenes and Streptococcus pneumoniae were detected, except erm (TR) gene. The genetic elements carrying resistance determinants showed significant interspecies similarities, indicating conjugative transfer of antibiotic resistance genes between streptococcal species. Conclusion: Identification of the novel antibiotic resistance genes in SDSE indicates the necessity of monitoring of antibiotic resistance spreading and gene transfer in this bacterium.

Streptococcus pyogenes carriage acquisition, persistence and transmission dynamics within households in The Gambia (SpyCATS): protocol for a longitudinal household cohort study

Background Streptococcus pyogenes (StrepA) causes a significant burden of disease globally from superficial infections to invasive disease. It is responsible for over 500,000 deaths each year, predominantly in low- and middle-income countries (LMIC). Superficial StrepA infections of the skin and pharynx can lead to rheumatic heart disease, the largest cause of StrepA-related deaths in LMIC. StrepA can also asymptomatically colonise normal skin and the pharynx (carriage), potentially increasing infection risk. Streptococcus dysgalactiae subsp. equisimilis (SDSE) carriage is also common in LMIC and may interact with StrepA. This study aims to investigate StrepA and SDSE carriage and infection epidemiology, transmission dynamics and naturally acquired immunity within households in The Gambia. Methods A longitudinal household observational cohort study will be conducted over one year. 45 households will be recruited from the urban area of Sukuta, The Gambia, resulting in approximately 450 participants. Households will be visited monthly, and available participants will undergo oropharyngeal and normal skin swabbing. Incident cases of pharyngitis and pyoderma will be captured via active case reporting, with swabs taken from disease sites. Swabs will be cultured for the presence of group A, C and G beta-haemolytic streptococci. Isolates will undergo whole genome sequencing. At each visit, clinical, socio-demographic and social mixing data will be collected. Blood serum will be collected at baseline and final visit. Oral fluid and dried blood spot samples will be collected at each visit. Mucosal and serum anti-StrepA antibody responses will be measured. Outcome This study will report StrepA and SDSE clinical epidemiology, risk factors, transmission dynamics, and serological responses to carriage and infection. Detailed social mixing behaviour will be combined with phylogenetic relatedness to model the extent of transmission occurring withing and between households. The study will provide data to help meet global strategic StrepA research goals.

Antimicrobial Resistance among Beta-Hemolytic Streptococcus in Brazil: An Overview.

Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus dysgalactiae subsp. equisimilis (SDSE) are the beta-hemolytic streptococci species with the most clinical relevance to humans. These species are responsible for several infections, ranging from mild to life-threatening diseases. Although resistance to recommended drugs has not been so critical as detected in other species, it has occurred in diverse regions. In Brazil, it is possible to observe an increasing macrolide and lincosamide resistance trend due to the spread of polyclonal strains. Macrolide–lincosamide–streptogramin B (MLS) resistance phenotypes have been prevalent among S. agalactiae and S. pyogenes, while M phenotype (resistance only to macrolides) has prevailed among SDSE resistant isolates. Fluoroquinolone resistance is rare in this country, reported only in S. agalactiae and S. pyogenes. This is due to nucleotide substitutions in gyrA and parC genes. Reduced penicillin susceptibility and vancomycin resistance, detected in other regions, have not yet been reported in Brazil. Tetracycline is not a therapeutical option, and resistance has occurred at high levels, especially among S. agalactiae. These findings highlight the need for continuous monitoring in order to track the occurrence of antimicrobial resistance among beta-hemolytic streptococci species circulating in this country.

Streptococcus dysgalactiae subsp. equisimilis from invasive and non-invasive infections in Spain: combining epidemiology, molecular characterization, and genetic diversity.

The purpose of this study was to characterize the antibiotic resistance, virulence, and genetic diversity among invasive and non-invasive Streptococcus dysgalactiae subsp. equisimilis (SDSE) isolates. SDSE were isolated from clinical samples of outpatients and inpatients cares in La Rioja region (Spain) during 2012-2015. The analyses performed were susceptibility testing by disc diffusion, resistance and virulence genes by PCR, emm typing by PCR and sequencing, and other molecular typing by SmaI-PFGE and MLST. Forty-two SDSE isolates were recovered (64.3% non-invasive, 35.7% invasive) that were grouped in 31 PFGE patterns, 17 ST, and 14 emm types, being stC1400, stG6792, and stG62647 the most frequent, and stC74a and stC5345 exclusive in invasive SDSE. Twenty-one SDSE were resistant to at least one antibiotic. The erm(TR) and erm(B) genes were linked with resistance to macrolides; tet(M) and tet(T) to tetracycline; dfrF to trimethoprim; ant(6)-Ia and aph(3')-IIIa to aminoglycosides; and the substitutions Asp80Ala in GyrA and Ser79Phe in ParC with resistance to levofloxacin. The sagA, slo, scpA, and ska virulence genes were amplified in 93% SDSE. Streptococcal superantigenic speGdys gene was identified in 80% of invasive and 63% of non-invasive SDSE and correlated with certain emm types (e.g., stG62647 or stG6792). SDSE invasive infections were most frequent in elderly patients, and half of our SDSE were resistant to at least one antibiotic tested. This work is the first detection of tet(T), dfrF, and new substitution in GyrA protein in SDSE. A high diversity of circulating genetic lineages was found among our SDSE.

Novel Hyaluronate Lyase Involved in Pathogenicity of Streptococcus dysgalactiae subsp. equisimilis.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes cellulitis, bacteremia, and invasive diseases, such as streptococcal toxic shock syndrome. Although SDSE infection is more prevalent among elderly individuals and those with diabetes mellitus than infections with Streptococcus pyogenes (Group A streptococci; GAS) and Streptococcus agalactiae (Group B streptococci; GBS), the mechanisms underlying the pathogenicity of SDSE remain unknown. SDSE possesses a gene hylD encoding a hyaluronate lyase (HylD), whose homologue (HylB) is involved in pathogenicity of GBS, while the role of HylD has not been characterized. In this study, we focused on the enzyme HylD produced by SDSE; HylD cleaves hyaluronate (HA) and generates unsaturated disaccharides via a β-elimination reaction. Hyaluronate-agar plate assays revealed that SDSE promoted dramatic HA degradation. SDSE expresses both HylD and an unsaturated glucuronyl hydrolase (UGL) that catalyzes the degradation of HA-derived oligosaccharides; as such, SDSE was more effective at HA degradation than other β-hemolytic streptococci, including GAS and GBS. Although HylD shows some homology to HylB, a similar enzyme produced by GBS, HylD exhibited significantly higher enzymatic activity than HylB at pH 6.0, conditions that are detected in the skin of both elderly individuals and those with diabetes mellitus. We also detected upregulation of transcripts from hylD and ugl genes from SDSE wild-type collected from the mouse peritoneal cavity; upregulated expression of ugl was not observed in ΔhylD SDSE mutants. These results suggested that disaccharides produced by the actions of HylD are capable of triggering downstream pathways that catalyze their destruction. Furthermore, we determined that infection with SDSEΔhylD was significantly less lethal than infection with the parent strain. When mouse skin wounds were infected for 2 days, intensive infiltration of neutrophils was observed around the wound areas infected with SDSE wild-type but not SDSEΔhylD. Our investigation suggested that HylD and UGL play important roles in nutrient acquisition from hosts, followed by the bacterial pathogenicity damaging host tissues.

Pathogenicity Characterization of Prevalent-Type Streptococcus dysgalactiae subsp. equisimilis Strains.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging human pathogen that causes severe invasive streptococcal diseases. Recent reports have shown that SDSE exhibits high pathogenicity with different mechanisms from that of Streptococcus pyogenes, although the two streptococci possess some common virulence factors such as streptolysin, streptokinase, and cell-binding proteins. To date, only a few studies have examined the variety of mechanisms expressing the pathogenicity of SDSE. Among nine SDSE clinical isolates sequenced in this study, we present in vitro and in vivo analyses of KNZ01 and KNZ03, whose emm and multilocus species types (MLSTs) are prevalent in Japan and other countries. For the comparison of pathogenicity, we also utilized the ATCC 12394 strain. The whole-genome analysis showed that KNZ03 and ATCC 12394 are categorized into an identical clonal complex by MLST and are phylogenetically close. However, the three strains exhibited different characteristics for pathogenicity in vitro; ATCC 12394 showed significant cytotoxicity to human keratinocytes and release of streptolysin O (SLO) compared to KNZ01 and KNZ03; KNZ03 exhibited significantly high hemolytic activity, but did not secrete SLO. KNZ01 and KNZ03 adhered to human keratinocytes at a higher rate than ATCC 12394; KNZ03 showed a higher rate of survival after a brief (30 min) incubation with human neutrophils compared to the other two strains; also, KNZ01 grew more rapidly in the presence of human serum. In vivo subcutaneous infection commonly resulted in ulcer formation in the three strains 7 days after infection. KNZ01-infected mice showed significant body weight loss 2 days after infection. Besides, on post-infection day 2, only KNZ01 remained in the cutaneous tissues of mice. Scanning electron microscopy analysis revealed that KNZ01 formed an extracellular structure (biofilm), which was probably composed of cell wall-anchoring proteins, in the presence of glucose and human serum. The extracellular structure of ATCC 12394 was also changed dramatically in response to culture conditions, whereas that of KNZ03 did not. Our study proposed that each SDSE strain possesses different virulence factors characteristics for mediating pathogenicity in humans.

Prevalence and genomic characterization of Group A Streptococcus dysgalactiae subsp. equisimilis isolated from patients with invasive infections in Toyama prefecture, Japan

Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes severe invasive streptococcal infections, especially in elderly people. Between 2013 and 2018, 88 streptococci were isolated from clinical blood culture in a hospital in Toyama prefecture, Japan. The collection included six Group A SDSE (ASD) strains, which are rarely isolated. Multilocus sequence typing categorized five of the six strains into ST128 and the remaining strain into a new type. Maximum-likelihood phylogenetic analysis revealed that the six ASD strains had highly similar genome sequences. Bayesian analysis indicated that the most recent common ancestor of the strains appeared 39 years ago. The ASD strains possessed carbohydrate synthase genes that are conserved in Streptococcus pyogenes strains, whereas one strain featured a different arrangement of the gene cluster. The carbohydrate synthase genes varied by Lancefield type (A, C, and G).

Prevalence and long-term persistence of beta-haemolytic streptococci throat carriage among children and young adults.

Introduction. Among beta-haemolytic streptococci, Streptococcus pyogenes (GAS) is the prototype agent of bacterial pharyngitis and causes other human infections. Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes GAS-like infections, while Streptococcus agalactiae (GBS) is a common neonate pathogen that is rarely associated with pharyngitis.Aim. To determine the prevalence and persistence of beta-haemolytic streptococci throat carriage and type the bacterial population.Methods. Throat swabs were collected from 121 children and 127 young adult volunteers and cultured. Colonized volunteers were screened quarterly, for up to 1 year, while beta-haemolytic streptococci could be detected. Isolates were identified and submitted to antimicrobial susceptibility testing and epidemiological typing.Results. Carriage was detected in 34 (13.7 %) volunteers. Seventeen children carried GAS (14 %), while 17 young adults carried SDSE (8, 6.3 %), GBS (4, 3.1 %), GAS (3, 2.4 %) and the Streptococcus anginosus group (2, 1.6 %). Persistent carriage was detected for up to 6 months in two children and for up to 1 year in three young adults. Three new emm subtypes were found, emm87.16 and emm90.9 (GAS) and stC36.11 (SDSE). While the GAS population among children was unexpectedly clonal, substantial genetic diversity was found among the isolates recovered from young adults. Resistance to erythromycin, clindamycin and tetracycline was detected in GAS, GBS and SDSE recovered from young adults.Conclusions. Prevalence was slightly greater among children, but persistent carriage was greater among young adults, with SDSE being the species most associated with persistence. Few sources seemed to disseminate GAS among children, since only two clonal types were found. The volunteers hosted pathogenic streptococci persistently, including macrolide-resistant strains.

Infections Caused by Group C and G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis and Others): Epidemiological and Clinical Aspects.

Streptococci carrying serogroup C and G antigens, and in particular, Streptococcus dysgalactiae subsp. equisimilis (SDSE), are emerging human pathogens that are increasingly isolated from patients with a myriad of infections that range from mundane to life-threatening. SDSE is microbiologically similar to Streptococcus pyogenes. These streptococci frequently cause infections of the throat and skin and soft tissues. Moreover, they may invade the bloodstream and disseminate widely to many deep tissue sites, including the endocardium. Life-threatening invasive infections due to SDSE, including the streptococcal toxic shock syndrome, occur most frequently in patients with severe underlying medical diseases. Treatment with penicillin is adequate under most circumstances, but treatment failure occurs. SDSE may also be resistant to other antibiotic classes including tetracyclines, macrolides, and clindamycin. Most human infections caused by groups C and G streptococci are transmitted from person to person, but infections due to Streptococcus equi subsp. zooepidemicus (and, rarely, to S. equi subsp. equi) are zoonoses. Transmission of these latter species occurs by animal contact or by contamination of food products and has been associated with the development of poststreptococcal glomerulonephritis. Members of the Streptococcus anginosus group, usually classified with the viridans group of streptococci, are associated with a variety of pyogenic infections.

Homologous role of CovRS two-component regulatory system in NAD+ -glycohydrolase activity in Streptococcus dysgalactiae subsp. equisimilis as in Streptococcus pyogenes.

Streptococcal toxic shock syndrome (STSS) is primarily caused by Streptococcus pyogenes, but it may also be caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE). The analyses of S.pyogenes have revealed the important roles of NAD+ -glycohydrolase (Nga) and CovR/CovS, a two-component regulatory system. We examined these factors in SDSE by analyzing mainly two isogenic SDSE strains (12-10-1 and 12-10-3) from the blood of a patient with STSS. The Nga activities were measured and the nucleotide sequences of covR and covS genes were determined. We detected one nucleotide difference between the covR gene of 12-10-1 and that of 12-10-3, and the Nga activity of 12-10-1 was approximately 6.8-fold more than that of 12-10-3. The introduction of covR of 12-10-3 into 12-10-1 significantly reduced the Nga activity, but the introduction of 12-10-1 covR into itself had only a little effect. In addition, the knockout of covR or covS of 12-10-3 remarkably increased the Nga activity. We are the first to report that strains with wild-type and mutated covR were isolated simultaneously from an SDSE STSS patient and that the CovR/CovS two-component regulatory system is involved in the Nga activity in SDSE as well as in S.pyogenes.

Pathogenicity Induced by Invasive Infection of Streptococcus dysgalactiae subsp. equisimilis in a Mouse Model of Diabetes.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes severe invasive diseases such as streptococcal toxic shock syndrome, similar to that caused by S. pyogenes (GAS). Invasive SDSE infections are increasing, particularly among patients with diabetes mellitus. Here we investigate the association between the pathogenicity of SDSE and diabetes mellitus in a mouse model, using GAS infection for comparison. Intraperitoneal injection of highly hemolytic SDSE-167 into C57BL6/J mice induced a rapid rise in blood glucose concentrations within 4 h, which was otherwise seen only in mice injected with high doses of hypervirulent GAS mutants. The survival rates of mice injected with SDSE-167 were significantly lower in mice (db/db) with type 2 diabetes than in nondiabetic mice. Injection of db/db mice with SDSE-167 increased the concentrations of cytokines and chemokines, particularly those of interleukin 6 and monocyte chemotactic protein-1. Microarray data indicate that multiple pathways are involved in the pathogenicity of SDSE-167 in db/db mice. These data reveal that the mechanisms underlying streptococcal infection differ between SDSE and GAS.

Detection of Streptococcus pyogenes virulence genes in Streptococcus dysgalactiae subsp. equisimilis from Vellore, India.

Streptococcus dysgalactiae subsp. equisimilis (SDSE), belonging to the group C and G streptococci, are human pathogens reported to cause clinical manifestations similar to infections caused by Streptococcus pyogenes. To scrutinize the distribution of gene coding for S. pyogenes virulence factors in SDSE, 255 isolates were collected from humans infected with SDSE in Vellore, a region in southern India, with high incidence of SDSE infections. Initial evaluation indicated SDSE isolates comprising of 82.35% group G and 17.64% group C. A multiplex PCR system was used to detect 21 gene encoding virulence-associated factors of S. pyogenes, like superantigens, DNases, proteinases, and other immune modulatory toxins. As validated by DNA sequencing of the PCR products, sequences homologous to speC, speG, speH, speI, speL, ssa and smeZ of the family of superantigen coding genes and for DNases like sdaD and sdc were detected in the SDSE collection. Furthermore, there was high abundance (48.12% in group G and 86.6% in group C SDSE) of scpA, the gene coding for C5a peptidase in these isolates. Higher abundance of S. pyogenes virulence factor genes was observed in SDSE of Lancefield group C as compared to group G, even though the incidence rates in former were lower. This study not only substantiates detection of S. pyogenes virulence factor genes in whole genome sequenced SDSE but also makes significant contribution towards the understanding of SDSE and its increasing virulence potential.

Molecular Epidemiological Features and Antibiotic Susceptibility Patterns of Streptococcus dysgalactiae subsp. equisimilis Isolates from Korea and Japan.

BackgroundThe molecular characterization of Streptococcus dysgalactiae subsp. equisimilis (SDSE) has not yet been performed in Korea. This study aimed to find the differences or similarities in the clinical features, molecular epidemiological findings, and antimicrobial resistance patterns of SDSE from two countries (Korea and Japan).MethodsSDSE isolates were collected from Korea (N=69) from 2012–2016 and Japan (N=71) from 2014–2016. Clinical characteristics, emm genotypes, and sequence types (STs) were compared. Microdilution tests were performed using different antimicrobials, and their resistance determinants were screened.ResultsMedian ages were 69 years in Korea and 76 years in Japan. The most common underlying diseases were diabetes and malignancy. Blood-derived isolates comprised 36.2% and 50.7% of Korean and Japanese isolates, respectively; mortality was not different between the two groups (5.8% vs 9.9%, P=0.53). Among Korean isolates with 20 different combined ST-emm types, ST127-stG245 (N=16), ST128-stG485 (N=10), and ST138-stG652 (N=8) were prevalent. Among Japanese isolates with 29 different combined types, ST17-stG6792 (N=11), ST29-stG485 (N=7), and ST205-stG6792 (N=6) were prevalent. Resistance rates to erythromycin, clindamycin, and minocycline were 34.8%, 17.4%, and 30.4% in Korea and 28.2%, 14.1%, and 21.4% in Japan, respectively.ConclusionsSDSE infections commonly occurred in elderly persons with underlying diseases. There was a significant difference in the distribution of ST-emm types between the two countries. Antimicrobial resistance rates were comparable with different frequencies of resistance determinants in each country.