Search

Streptococcus pyogenes (Group A Streptococcus - GAS) is a human pathogen causing wide range of infections and toxin-mediated diseases in human beings of all age groups with fatality of 10–30 %. The limited success of antibiotics and the non-availability of vaccines makes GAS a global burden. The multi-subunit RNA polymerase (RNAP) is a validated bacterial therapeutic target as it is involved in transcription and can arrest growth. Of the five subunits of this enzyme complex, the β-subunit (RpoC) has attracted specific attention as a drug target, particularly in the switch region. Here we attempt to repurpose non-antimicrobial drugs to act as RpoC inhibitors against S. pyogenes. In this study, 1826 FDA approved drugs have been identified through high-throughput virtual screening. Free Energy Perturbation (FEP) based binding free energy calculations have been performed at the final step of the virtual screening funnel to ensure high accuracy in silico results. Three compounds identified have been tested for susceptibility of S. pyogenes MTCC 442 strain and two antibiotic-resistant clinical isolates of S. pyogenes using microdilution assay. Among the three, two drugs Amlodipine Besylate (Amd) and Ranitidine hydrochloride (Rnt) have shown inhibition against all the tested strains and its mechanism of interaction with RpoC has been studied. The docked complexes were analyzed to understand the binding mode of the drugs to the target. Classical Molecular Dynamics studies for RpoC-Rnt complex and the two stable conformations of RpoC-Amd complex was carried out. Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (RoG) and Solvent Accessible Surface Area (SASA) of the complexes were plotted and studied. The thermodynamic parameters of protein-drug were experimentally determined using Isothermal Titration Calorimetry (ITC). Infrared spectroscopic studies and Fluorescence quenching studies provided insights into the secondary structural changes in RpoC on binding to the drugs. • FDA approved drugs have been screened to identify compounds that can bind to RNA polymerase β'subunit of Streptococcus pyogenes from a database of 1826 drugs. • Three compounds with optimum binding free energy were tested for antibacterial activity against drug-resistant clinical and standard MTCC strains of S. pyogenes. • Two compounds showing promising activity were further validated experimentally using biophysical techniques such as ITC, FT-IR and fluorescence spectroscopy. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes (Group A streptococci: GAS) are known to cause a wide variety of human illnesses, some of which can be life-threatening. Usually, penicillin is the first-choice agent for the treatment of GAS infections. For patients with penicillin or beta-lactam antibiotics allergies, macrolide drugs are recommended as an alternative therapy. However, an increased prevalence of macrolide-resistant GAS (MRGAS) has been reported in many countries. Furthermore, fluoroquinolone non-susceptible GAS has been reported. The present study was focused on determining the features of fluoroquinolone non-susceptible strains collected from children with pharyngotonsillitis in the southwestern areas of Japan. To reveal the characteristics of fluoroquinolone non-susceptible GAS, we investigated the MIC, T-serotype, emm typing, and PFGE of 298 GAS strains isolated in the Fukuoka southwest area of Japan between 2011 and 2013. We determined that fluoroquinolone non-susceptibility shows a MIC to tosufloxacin of ≧1 μg/ml. We identified 33 (11.1%) fluoroquinolone non-susceptible GAS strains. In these strains, 6 T-serotypes and 9 emm /MLST patterns were detected. The predominant combinations were emm 6/ST382 (14 strains, 42.4%) and emm 89/ST101 (5 strains, 15.2%). PFGE classified 10 pulsotypes, and each was quite different. These results showed that fluoroquinolone non-susceptible GAS strains have a variety of origins. The usage of fluoroquinolone drugs could have a negative effect on the antimicrobial drug sensitivity of GAS in Japan. Considering such a situation, continuous monitoring of quinolone non-susceptible GAS is necessary. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus and Streptococcus pyogenes are the causative agents of cellulitis, a bacterial skin infection. Cellulitis primarily affects the skin, and it later spreads to the other parts of the body, especially through the lymph nodes and bloodstream. Without proper medication, it becomes life-threatening. The main symptoms include inflammation, tenderness, tight and swollen skin, and fever. Vaccines using epitopes as antigens trigger quick immune responses; in addition, they are cost effective. These antigens are derived from bacterial proteins. In this study, virulence factors from membrane proteins such as sak, tst, isdA, clfB, and can from S. aureus (Fig. 1) and SPy, scpA, and hylp1 from S. p yogenes (Fig. 2) were selected for predicting the vaccine epitopes. VaxiJen server was used to evaluate the antigenicity of the selected proteins; BCPred, AAPPred, and ABCpred were used for B-cell epitope prediction, while ProPred and ProPred I were used for T-cell epitope prediction. MHCPred was used for the selected alleles, DRB1*0101 and DRB1*0401. Pepitope server was used for epitope mapping of the selected peptides. Epitopes that are common among those from BCPred, AAPPred, and ABCpred were selected: LKYGPKFDK (tst) and MTFDDKNGK (cna) from S. aureus and YTNSDKGGS (SPy), FKIEPDTTV (SPy), MTPSERLDL (scpA), VKTDDQQDK (scpA), and LKFKPAATV (hylp1) from S. pyogenes. Among them, YTNSDKGGS, MTPSERLDL, and MTFDDKNGK, were identified as suitable vaccine candidates for eliciting immune responses. These results of this study can be used to create a peptide-based vaccine for preventing cellulitis. [ABSTRACT FROM AUTHOR]

A newly developed MLVA seven-loci scheme for Streptococcus pyogenes is described. The method can be successfully applied by using both agarose gel with visual inspections of bands and Lab on Chip technology. The potential of the present MLVA has been tested on a collection of 100 clinical GAS strains representing the most common emm types found in high-income countries plus 18 published gap-free genomes, in comparison to PFGE and MLST. The MLVA analysis defined 30 MLVA types with ten out of the considered 15 emm types exhibiting multiple and specific MLVA types. In only one occasion the same MLVA profile was shared between isolates belonging to two different emm types. A robust congruency between the methods was observed, with MLVA discriminating within clonal complexes as defined by PFGE or MLST. This new MLVA scheme can be adopted as a quick, low-cost and reliable typing method to track the short-term diffusion of GAS clones in inter-laboratory-based surveillance. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes is commonly found on pharynx, mouth and rarely on skin, lower gastrointestinal tract. It is a potential pathogen causing tonsillitis, pneumonia, endocarditis. The present study was undertaken to study the effects of low shear modeled microgravity on growth, morphology, antibiotic resistance, cross-stress resistance to various stresses and alteration in gene expression of S. pyogenes . The growth analysis performed using UV–Visible spectroscopy indicated decrease in growth of S. pyogenes under low shear modeled microgravity. Morphological analysis by Bio-transmission electron microscopy (TEM), Bio-scanning electron microscopy (SEM) did not reveal much difference between normal and low shear modeled microgravity grown S. pyogenes . The sensitivity of S. pyogenes to antibiotics ampicillin, penicillin, streptomycin, kanamycin, hygromycin, rifampicin indicates that the bacterium is resistant to hygromycin. Further S. pyogenes cultured under low shear modeled microgravity was found to be more sensitive to ampicillin and rifampicin as compared with normal gravity grown S. pyogenes . The bacteria were tested for the acid, osmotic, temperature and oxidative cross stress resistances. The gene expression of S. pyogenes under low shear modeled microgravity analyzed by microarray revealed upregulation of 26 genes and down regulation of 22 genes by a fold change of 1.5. [ABSTRACT FROM AUTHOR]

The important human gram positive bacterial pathogen Streptococcus pyogenes employs various virulence factors to promote inflammation and to facilitate invasive disease progression. In this study we explored the relation of the secreted streptococcal cysteine proteases IdeS and SpeB, and neutrophil (PMN) proteases. We found that SpeB is resistant to proteolytic attack in an inflammatory environment, emphasizing the importance of SpeB for streptococcal pathogenicity, while PMN enzymes and SpeB itself process the IgG degrading endopeptidase IdeS. Processing occurs as NH 2 -terminal cleavage of IdeS resulting in reduced immunorecognition of the protease by specific antibodies. While the endopeptidase retains IgG cleaving activity, its ability to suppress the generation of reactive oxygen species is abolished. We suggest that the cleavage of NH 2 -terminal peptides by SpeB and/or neutrophil proteases is a mechanism evolved to prevent early inactivation of this important streptococcal virulence factor, albeit at the cost of impaired functionality. [ABSTRACT FROM AUTHOR]

Objectives The primary objective of our study was to obtain susceptibility data for josamycin against Streptococcus pyogenes isolated from patients presenting with upper respiratory tract infections in France. The secondary objective was to characterize the molecular mechanism of resistance in macrolide-resistant isolates. Patients and methods MICs of erythromycin, clarithromycin, azithromycin, josamycin, and clindamycin were determined by the broth microdilution method. Resistance genes erm (B), erm (TR), and mef (A) were screened by PCR. Results The MIC 50 and MIC 90 of josamycin against 193 isolates of S. pyogenes were 0.12 and 0.25 mg/L, respectively, with a resistance rate estimated at 4.7%. Resistance was due to the erm (B) gene whereas strains harboring erm (TR) or mef (A) remained susceptible. Conclusions Josamycin was active against >95% of S. pyogenes isolated from patients with upper respiratory tract infections, and can be used as an alternative for the treatment of pharyngitis. [ABSTRACT FROM AUTHOR]

Abstract: Streptococcus pyogenes infections remain a health problem in several countries because of post-streptococcal sequelae, such as rheumatic fever and rheumatic heart disease. We developed a vaccine epitope (StreptInCor) composed of 55 amino acid residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. Recently, by using human blood samples, we showed that the StreptInCor epitope is able to bind to different HLA class II molecules and that it could be considered a universal vaccine epitope. In the present work, we evaluated the immune response of HLA class II transgenic mice against aluminum hydroxide-absorbed StreptInCor. After a period of one year, several organs were analyzed histologically to verify the safety of the candidate vaccine epitope. Our results showed that StreptInCor is able to induce robust and safe and long lasting immune response without deleterious reactions in several organs. In conclusion, the results presented here indicate that StreptInCor could be considered a safe vaccine against severe streptococcus-induced diseases. [Copyright &y& Elsevier]

Abstract: To investigate the antimicrobial resistance trends and the distribution of emm types of group A streptococci (GAS), we examined 1160 clinical isolates of GAS collected between 2003 and 2006. Susceptibilities to commonly used antimicrobial agents were determined by Etest, and macrolide resistance genes were detected by polymerase chain reaction (PCR). GAS isolates were typed by polymerase chain reaction PCR and sequencing of emm gene. The rates of resistance to erythromycin (ERY), clindamycin, azithromycin, tetracycline, and chloramphenicol were 14.9%, 1.4%, 14.9%, 18.9%, 0.6%, respectively. None of the isolates exhibited resistance to penicillin, ceftriaxone, linezolid, moxifloxacin, rifampicin, or vancomycin. Macrolide resistance increased from 12.1% in 2003 to 18.8% in 2006 (P = 0.02). Of 173 ERY-resistant GAS isolates, 93 (53.7%) harbored the mefA gene, 70 (40.4%) the ermA, and 10 (5.8%) the ermB. Eighty percent of the observed emm types are covered by the proposed 26-valent GAS vaccine. Among 173 ERY-resistant isolates, the predominant emm types were 12 (19.5%), 77 (17.9%), and 4 (16.8%), and among 770 ERY-susceptible isolates, the predominant types were 1 (18.8%), 12 (17.5%), 28 (13.8%). The observed antimicrobial resistance trends and the distribution of specific emm types have implications in guiding empiric therapy and in developing vaccine strategies to prevent GAS infections. [Copyright &y& Elsevier]

Abstract: The important human bacterial pathogen Streptococcus pyogenes has evolved a variety of mechanisms to evade the actions of the human immune system. M protein and M-like proteins are major virulence factors that bind with high affinity to the Fc-part of IgG. However, the contribution of non-immune binding of IgG to bacterial virulence is not fully established. Importantly, the capacity of S. pyogenes to bind IgG is limited and due to the presence of large amounts of IgG present in vivo, the majority of IgGFc binding sites at the streptococcal surface are likely to be occupied by non-specific IgG. S. pyogenes also secretes a highly effective IgG-endopeptidase, IdeS that inhibits phagocytic killing by cleavage of specific IgG creating F(ab′)2 and 1/2Fc fragments. In the present work, IgG and 1/2Fc binding to the streptococcal surface was studied and correlated to IdeS activity. Binding of IgG to the streptococcal surface is shown to be equilibrium and thus not designed to mediate a lasting protection against specific antibodies. However, non-immune binding of IgG to the bacterial surface is followed by the proteolytic cleavage of the antibody by the IgG-endopeptidase IdeS. IdeS generated 1/2Fc fragments do not compete efficiently with intact IgG in binding to the bacterial surface and rapid dissociation of 1/2Fc allows binding of new IgG. Thus, a correlated binding and proteolytic cleavage of IgG also increases the probability that the bacteria can resist specific IgG, despite the presence of a large excess of non-specific IgG in the circulation. As a consequence of IdeS activity, circulating 1/2Fc fragments are generated. These 1/2Fc fragments were shown to be biological active by acting as priming agents for polymorphonuclear leucocytes, suggesting a new mechanism of immune evasion employed by S. pyogenes. [Copyright &y& Elsevier]

The increase detected in macrolide resistance in streptococci in various parts of the world has brought into question the usefulness of macrolides as first line therapy for respiratory tract infections. In a nationwide study, a total of 3012 Streptococcus pneumoniae and 499 Streptococcus pyogenes isolates were collected from 1996 to 2002 and tested for their susceptibility to penicillin, azithromycin, clarithromycin and telithromycin (2002 only). Penicillin-intermediate and -resistant isolates of S. pneumoniae comprised 4.9% (2.9 and 2.0%, respectively) of all isolates in 1996; macrolide resistance was also comparatively low at 3.2%. In the following years the rate of penicillin-resistant pneumococci increased steadily, reaching the 10% mark in 2002. A similar trend was recorded for the macrolides. No penicillin-resistant strain of S. pyogenes was found during the observation period. The prevalence of macrolide-resistance in S. pyogenes climbed from 4.7% in 1996 to the present rate of 7.2% (clarithromycin) and 9.4% (azithromycin). Telithromycin showed excellent activity against both S. pneumoniae and S. pyogenes with 99.8 and 100% strains sensitive, respectively. [Copyright &y& Elsevier]

In the present study, a real-time PCR protocol was developed for the detection of macrolide resistance determinants and was validated in a nationwide study in Germany covering a total of 236 Streptococcus pyogenes and 241 Streptococcus pneumoniae strains collected from children ≤16 years of age with community-acquired infections. Macrolide resistance was observed in 19.9% of pneumococcal strains and 14% of S. pyogenes isolates. Of the erythromycin A-resistant S. pyogenes strains, 93.9% showed the efflux type mef(A); 62.5% of the S. pneumoniae strains were mef(A)- and 37.5% erm(B)-positive. The correlation of the results of real-time PCR assay genotyping in the present study compared with those of conventional PCR genotyping and resistance phenotyping was 100%. Macrolide resistance is of growing concern in Germany. This highly sensitive and specific PCR assay to detect macrolide resistance has the potential to provide sufficiently rapid results to improve antibiotic treatment of streptococcal infections. [Copyright &y& Elsevier]

The objective of this study was to consider the invasive properties of Streptococcus pyogenes in human pharyngeal epithelial cells, and to correlate these with their clinical significance. Clinical isolates of S. pyogenes obtained from blood cultures over a period of 10 years, and throat and skin isolates from a community-based study, were used in this investigation. The S. pyogenes isolates were inoculated in HEp-2 cells and subsequently treated with antibiotics to kill the extracellular bacteria. The cells were then lyzed, and a colony count was carried out to check for invasion. The throat and skin isolates had 45.7%, 25.7% and 28.5% of low, intermediate and high invasion efficiencies, respectively, while 80%, 8.6% and 11.4% of the blood isolates had low, intermediate and high invasion efficiencies. We concluded that the throat and the skin isolates from superficial infections were more invasive than the blood isolates, which is an interesting and paradoxical feature. [ABSTRACT FROM AUTHOR]

Abstract: Superantigens (SAgs) include a class of certain bacterial and viral proteins exhibiting highly potent lymphocyte-transforming (mitogenic) activity towards human and or other mammalian T lymphocytes. Unlike conventional antigens, SAgs bind to certain regions of major histocompatibility complex (MHC) class II molecules of antigen-presenting cells (APCs) outside the classical antigen-binding groove and concomitantly bind in their native form to T cells at specific motifs of the variable region of the ? chain (V?) of the T cell receptor (TcR). This interaction triggers the activation (proliferation) of the targeted T lymphocytes and leads to the in vivo or in vitro release of high amounts of various cytokines and other effectors by immune cells. Each SAg interacts specifically with a characteristic set of V? motifs. The review summarizes our current knowledge on S. aureus and S. pyogenes superantigen proteins. The repertoire of the staphylococcal and streptococcal SAgs comprises 24 and 8 proteins, respectively. The staphylococcal SAgs include (i) the classical enterotoxins A, B, C (and antigenic variants), D, E, and the recently discovered enterotoxins G to Q, (ii) toxic shock syndrome toxin-1, (iii) exfoliatins A and B. The streptococcal SAgs include the classical pyrogenic exotoxins A and C and the newly identified pyrogenic toxins, G, H, I, J, SMEZ, and SSA. The structural and genomic aspects of these toxins and their molecular relatedness are described as well as the available 3-D crystal structure of some of them and that of certain of their complexes with MHC class II molecules and the TcR, respectively. The pathophysiological properties and clinical disorders related to these SAgs are reviewed. [Copyright &y& Elsevier]

Objective: To assess the activity of levofloxacin against pneumococci and streptococci.Method: One thousand two hundred and fifty five strains of pneumococci (1015) and streptococci (240) was obtained from October 1999 to March 2000 in 46 participant centers: 35 hospital laboratories and 11 community laboratories. Susceptibilities were determined by the standard disc-diffusion test and MICs of beta-lactams (penicillin, amoxicillin, cefotaxime, cefpirome, cefpodoxime and cefuroxime) by Etest. MICs of levofloxacin were measured, for a sample of susceptible strains and for all strains that were resistant by disc-diffusion.Results: 41.3% and 31.1% of S. pneumoniae strains were susceptible, 34% and 57.4% intermediates, 24.7% and 11.5% were resistant to penicillin by Etest in hospital and in community laboratories, respectively. Percentages of susceptibilities to levofloxacin were of 98.2% (hospitals) and 100% (community), and of 41.2% (hospital) and 21.6% (community) to erythromycin. The highest percentage of non susceptible strains observed in the community was probably related to the fact that strains isolated in community mostly originated from children: 64.2% versus 26.5%.Susceptibility of Streptococcus pyogenes to penicillin remains constant, 100% of strains being susceptible. Macrolides still exhibit good activity against this species with 93.3% of susceptible strains to erythromycin. Percentage of susceptible strains of S. pyogenes was 97.8. Viridans group streptococci are less susceptible to antibiotics with 73.5% and 47% of strains being susceptible to penicillin and macrolides, respectively. 95.4% of strains were susceptible to levofloxacin.Conclusion: The results of this study show the good in vitro activity of levofloxacin against S. pneumoniae in hospital and in community. [Copyright &y& Elsevier]

Matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) has revolutionized bacterial identification. However, the phylogenetic resolution is still insufficient for discerning several β-haemolytic streptococcal species. We aimed to improve the diagnostic performance of MALDI-ToF through manual curation of the reference spectra in Brukers Compass Library DB-7854. Before intervention, only 133 out of 217 (62%) Streptococcus dysgalactiae isolates were successfully identified to the species level, 83 isolates were identified to the genus level as either S. dysgalactiae , S. pyogenes or S. canis , and one S. dysgalactiae isolate was wrongly identified as S. canis. All 109 S. canis isolates were successfully identified to the species level. Removal of three reference spectra from the database significantly improved the identification of S. dysgalactiae to 94%, without compromising identification of S. canis. This illustrates the advantage of refinement of the reference database in order to improve the analytic precision of MALDI-ToF. [ABSTRACT FROM AUTHOR]

Berberine is an isoquinoline alkaloid found in many plants. Although berberine is known to possess the antibacterial activity against Streptococcus pyogenes , the mechanism underlying it is not fully understood. In the current study, to investigate the molecular mechanism how berberine exerts its antibacterial effects, quantitative proteomics was conducted to investigate differential expressed proteins in S. pyogenes in response to berberine treatment. KEGG pathways analysis revealed that berberine regulated proteins were mainly involved in carbohydrate metabolism, fatty acid biosynthesis, pyrimidine metabolism, RNA degradation, ribosome, purine metabolism, DNA replication and repair and oxidative phosphorylation pathways. Moreover, we found that berberine induced the accumulation of reactive oxygen species (ROS), whereas inhibition of ROS generation with antioxidant N -acetyl L-cysteine could block the berberine induced antibacterial effects. Collectively, we demonstrated that berberine exerts its antibacterial effects by perturbing carbohydrate metabolism, which therefore generate ROS to damage the DNA, protein and lipids biosynthesis, ultimately trigger cell lethality. These findings provide novel insights into the mechanism of berberine as an antimicrobial drug to control diseases caused by S. pyogenes. Streptococcus pyogenes is the major cause of invasive bacterial disease in human, which leads to hundreds of million cases annually and over 500,000 deaths due to severe infections. Berberine is an isoquinoline alkaloid from medicinal plants, which possesses a variety of pharmacological effects including antibacterial. In this work, proteomic analysis revealed that berberine affected carbohydrate metabolism, DNA, protein and fatty acid biosynthesis and oxidative phosphorylation pathways in S. pyogenes. And further experimental results showed that berberine exerts its antibacterial effects against Streptococcus pyogenes by stimulated the generation of reactive oxygen species (ROS). These data provide novel insights into the effect of berberine on oxidative stress as an antimicrobial drug. Unlabelled Image • Berberine regulated the expression of proteins which involved in multiple pathways. • Berberine induced the accumulation of reactive oxygen species (ROS) to exert its antibacterial effects in S. pyogenes. • Antioxidant N-acetyl L-cysteine could block the berberine induced antibacterial effects. [ABSTRACT FROM AUTHOR]

• The study underscores S. pyogenes as a potential cause of respiratory illness in pets. • Emergence of multidrug-resistant S. pyogenes among pet animals. • Alarming public health community for the possible transmission of such strains to pet owners. Macrolide-resistant Streptococcus pyogenes is an emerging problem with a great public health concern throughout the world. The current study was carried out in order to investigate the possible role of pet animals in the epidemiology of such pathogen. For this purpose, nasal or oral swabs were collected from 115 pets (40 dogs and 75 cats) with respiratory illness. The collected swabs were cultured for isolation and identification of S. pyogenes. Macrolide-resistant S. pyogenes strains were initially identified after antibiotic susceptibility testing of the all obtained S. pyogenes isolates, then the phenotypic and molecular identification were done using the double-disk test and the detection of macrolide resistance genes, respectively. Of the 115 examined pet animals, S. pyogenes was recovered from 11 (9.6 %), from which, the isolation rates among dogs and cats were 15 % and 6.7 %, respectively. Macrolide-resistant S. pyogenes was isolated from dogs and cats in the following rates 10 % and 5.3 %, respectively. All macrolide-resistant S. pyogenes strains were assigned to cMLS resistance phenotype while all of them carried ermB gene only, except one strain from a cat possessed both ermB and ermTR genes. The phylogenetic analysis of 4 ermB gene sequences showed high genetic relatedness with those carried by bacteria isolated from human cases to underline the public health impact of such strains. Seriously, all macrolide-resistant S. pyogenes strains were resistant to penicillin. The emergence of penicillin-macrolide resistant S. pyogenes among pet animals underscores not only an emerging veterinary pathogen, but also an ongoing public health threat. [ABSTRACT FROM AUTHOR]

Group A Streptococcus (GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function—annotated subsequently as S protein—in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo , the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory. • S protein promotes red blood cell binding to group A Streptococcus (GAS) cell surface • Red blood cell membrane binding is an immune evasion tactic used by GAS • Lack of S protein results in a drastic reduction of virulence during systemic infection • Attenuated virulence during Δ ess infection is associated with altered immunity Wierzbicki et al. show that S protein is a major group A Streptococcus (GAS) virulence factor that facilitates bacterial coating with lysed red blood cells to promote molecular mimicry, which increases virulence in vitro and in vivo. Removal of S protein reduces the abundance of multiple virulence factors and attenuates virulence. [ABSTRACT FROM AUTHOR]

Introduction The signs of Streptococcus pyogenes , group A streptococci (GAS) bacteremia are non-specific and patients can have wide presentations ranging from flu-like symptoms to life-threatening toxic-shock syndrome in just a few hours. Case presentation We report a case of fulminant S. pyogenes sepsis in an elderly woman with septic arthritis and remarkable past medical history/risk factors. She was febrile, hypotensive and had a swollen and tender right knee. Multiple blood cultures and the synovial fluid culture yielded S. pyogenes . Despite adequate antimicrobial therapy with penicillin and clindamycin the patient succumbed to her infection within 4 days of presentation in our hospital. Conclusion GAS remains penicillin sensitive most of the time but prompt appropriate antibiotic therapy is very crucial to survival. [ABSTRACT FROM AUTHOR]

The worldwide spread of erythromycin A-resistant streptococci, including Streptococcus pneumoniae , is of concern. Many studies have demonstrated that the viridans group streptococci can be a reservoir of erythromycin A resistance. Within oral streptoccoci, an important difference in the susceptibility pattern has been noted. The purpose of this short editorial is to highlight the importance of this group of bacteria as a reservoir of resistance to erythromycin A and the possible transfer of resistance to S. pneumoniae and S. pyogenes. [ABSTRACT FROM AUTHOR]