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Sample records for streptococcus pyogenes disease

  1. Epidemiology of Severe Streptococcus pyogenes Disease in Europe?

    PubMed Central

    Lamagni, Theresa L.; Darenberg, Jessica; Luca-Harari, Bogdan; Siljander, Tuula; Efstratiou, Androulla; Henriques-Normark, Birgitta; Vuopio-Varkila, Jaana; Bouvet, Anne; Creti, Roberta; Ekelund, Kim; Koliou, Maria; Reinert, Ralf Ren; Stathi, Angeliki; Strakova, Lenka; Ungureanu, Vasilica; Schaln, Claes; Jasir, Aftab

    2008-01-01

    The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe. PMID:18463210

  2. Genetic manipulation of Streptococcus pyogenes (the Group A Streptococcus, GAS).

    PubMed

    Le Breton, Yoann; McIver, Kevin S

    2013-01-01

    Streptococcus pyogenes (the Group A Streptococcus, GAS) is a Gram-positive bacterium responsible for a wide spectrum of diseases ranging from mild superficial infections (pharyngitis, impetigo) to severe, often life-threatening invasive diseases (necrotizing fasciitis, streptococcal toxic shock syndrome) in humans. This unit describes molecular techniques for the genetic manipulation of S. pyogenes with detailed protocols for transformation, gene disruption, allelic exchange, transposon mutagenesis, and genetic complementation. PMID:24510894

  3. Genetic Manipulation of Streptococcus pyogenes (The Group A Streptococcus, GAS)

    PubMed Central

    Le Breton, Yoann; McIver, Kevin S.

    2013-01-01

    Streptococcus pyogenes (the group A streptococcus, GAS) is a Gram-positive bacterium responsible for a wide spectrum of diseases ranging from mild superficial infections (pharyngitis, impetigo) to severe often life-threatening invasive diseases (necrotizing fasciitis, streptococcal toxic shock syndrome) in humans. This unit describes molecular techniques for the genetic manipulation of S. pyogenes with detailed protocols for transformation, gene disruption, allelic exchange, transposon mutagenesis, and genetic complementation. PMID:24510894

  4. Clinical and Microbiological Characteristics of Severe Streptococcus pyogenes Disease in Europe?

    PubMed Central

    Luca-Harari, Bogdan; Darenberg, Jessica; Neal, Shona; Siljander, Tuula; Strakova, Lenka; Tanna, Asha; Creti, Roberta; Ekelund, Kim; Koliou, Maria; Tassios, Panayotis T.; van der Linden, Mark; Straut, Monica; Vuopio-Varkila, Jaana; Bouvet, Anne; Efstratiou, Androulla; Schaln, Claes; Henriques-Normark, Birgitta; Jasir, Aftab

    2009-01-01

    In an attempt to compare the epidemiology of severe Streptococcus pyogenes infection within Europe, prospective data were collected through the Strep-EURO program. Surveillance for severe cases of S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe by using a standardized case definition and questionnaire. Patient data as well as bacterial isolates were collected and characterized by T and M/emm typing, and selected strains were analyzed for the presence of superantigen genes. Data were analyzed to compare the clinical and microbiological patterns of the infections across the participating countries. A total of 4,353 isolates were collected from 5,521 cases with severe S. pyogenes infections who were identified. A wide diversity of M/emm types (n = 104) was found among the S. pyogenes clinical isolates, but the M/emm type distribution varied broadly between participating countries. The 10 most predominant M/emm types were M/emm type 1 (M/emm1), M/emm28, M/emm3, M/emm89, M/emm87, M/emm12, M/emm4, M/emm83, M/emm81, and M/emm5, in descending order. A correlation was found between some specific disease manifestations, the age of the patients, and the emm types. Although streptococcal toxic shock syndrome and necrotizing fasciitis were caused by a large number of types, they were particularly associated with M/emm1 and M/emm3. The emm types included in the 26-valent vaccine under development were generally well represented in the present material; 16 of the vaccine types accounted for 69% of isolates. The Strep-EURO collaborative program has contributed to enhancement of the knowledge of the spread of invasive disease caused by S. pyogenes within Europe and encourages future surveillance by the notification of cases and the characterization of strains, which are important for vaccination strategies and other health care issues. PMID:19158266

  5. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of -hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection. PMID:25456681

  6. Novel Regulatory Small RNAs in Streptococcus pyogenes

    PubMed Central

    Tesorero, Rafael A.; Yu, Ning; Wright, Jordan O.; Svencionis, Juan P.; Cheng, Qiang; Kim, Jeong-Ho; Cho, Kyu Hong

    2013-01-01

    Streptococcus pyogenes (Group A Streptococcus or GAS) is a Gram-positive bacterial pathogen that has shown complex modes of regulation of its virulence factors to cause diverse diseases. Bacterial small RNAs are regarded as novel widespread regulators of gene expression in response to environmental signals. Recent studies have revealed that several small RNAs (sRNAs) have an important role in S. pyogenes physiology and pathogenesis by regulating gene expression at the translational level. To search for new sRNAs in S. pyogenes, we performed a genomewide analysis through computational prediction followed by experimental verification. To overcome the limitation of low accuracy in computational prediction, we employed a combination of three different computational algorithms (sRNAPredict, eQRNA and RNAz). A total of 45 candidates were chosen based on the computational analysis, and their transcription was analyzed by reverse-transcriptase PCR and Northern blot. Through this process, we discovered 7 putative novel trans-acting sRNAs. Their abundance varied between different growth phases, suggesting that their expression is influenced by environmental or internal signals. Further, to screen target mRNAs of an sRNA, we employed differential RNA sequencing analysis. This study provides a significant resource for future study of small RNAs and their roles in physiology and pathogenesis of S. pyogenes. PMID:23762235

  7. Molecular typing of Chinese Streptococcus pyogenes isolates.

    PubMed

    You, Yuanhai; Wang, Haibin; Bi, Zhenwang; Walker, Mark; Peng, Xianhui; Hu, Bin; Zhou, Haijian; Song, Yanyan; Tao, Xiaoxia; Kou, Zengqiang; Meng, Fanliang; Zhang, Menghan; Bi, Zhenqiang; Luo, Fengji; Zhang, Jianzhong

    2015-06-01

    Streptococcus pyogenes causes human infections ranging from mild pharyngitis and impetigo to serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. The objective of this study was to compare molecular emm typing and pulsed field gel electrophoresis (PFGE) with multiple-locus variable-number tandem-repeat analysis (MLVA) for genotyping of Chinese S. pyogenes isolates. Molecular emm typing and PFGE were performed using standard protocols. Seven variable number tandem repeat (VNTR) loci reported in a previous study were used to genotype 169 S. pyogenes geographically-diverse isolates from China isolated from a variety of disease syndromes. Multiple-locus variable-number tandem-repeat analysis provided greater discrimination between isolates when compared to emm typing and PFGE. Removal of a single VNTR locus (Spy2) reduced the sensitivity by only 0.7%, which suggests that Spy2 was not informative for the isolates screened. The results presented support the use of MLVA as a powerful epidemiological tool for genotyping S. pyogenes clinical isolates. PMID:25843529

  8. Surface interactome in Streptococcus pyogenes.

    PubMed

    Galeotti, Cesira L; Bove, Elia; Pezzicoli, Alfredo; Nogarotto, Renzo; Norais, Nathalie; Pileri, Silvia; Lelli, Barbara; Falugi, Fabiana; Balloni, Sergio; Tedde, Vittorio; Chiarot, Emiliano; Bombaci, Mauro; Soriani, Marco; Bracci, Luisa; Grandi, Guido; Grifantini, Renata

    2012-04-01

    Very few studies have so far been dedicated to the systematic analysis of protein interactions occurring between surface and/or secreted proteins in bacteria. Such interactions are expected to play pivotal biological roles that deserve investigation. Taking advantage of the availability of a detailed map of surface and secreted proteins in Streptococcus pyogenes (group A Streptococcus (GAS)), we used protein array technology to define the "surface interactome" in this important human pathogen. Eighty-three proteins were spotted on glass slides in high density format, and each of the spotted proteins was probed for its capacity to interact with any of the immobilized proteins. A total of 146 interactions were identified, 25 of which classified as "reciprocal," namely, interactions that occur irrespective of which of the two partners was immobilized on the chip or in solution. Several of these interactions were validated by surface plasmon resonance and supported by confocal microscopy analysis of whole bacterial cells. By this approach, a number of interesting interactions have been discovered, including those occurring between OppA, DppA, PrsA, and TlpA, proteins known to be involved in protein folding and transport. These proteins, all localizing at the septum, might be part, together with HtrA, of the recently described ExPortal complex of GAS. Furthermore, SpeI was found to strongly interact with the metal transporters AdcA and Lmb. Because SpeI strictly requires zinc to exert its function, this finding provides evidence on how this superantigen, a major player in GAS pathogenesis, can acquire the metal in the host environment, where it is largely sequestered by carrier proteins. We believe that the approach proposed herein can lead to a deeper knowledge of the mechanisms underlying bacterial invasion, colonization, and pathogenesis. PMID:22199230

  9. [Neonatal Streptococcus pyogenes meningitis and sagittal sinus thrombosis: case report].

    PubMed

    Krebs, V L; Chieffi, L N; Jurfest, M E; Ceccon, R; Diniz, E M; Feferbaum, R; Takeuchi, C A; Marques-Dias, M J; Carneiro, J D; Vaz, F A

    1998-12-01

    We report a case of Streptococcus pyogenes meningitis in a 18 days year-old-girl with clinical course complicated by sagittal sinus thrombosis. Some aspects of the pathogenesis, treatment and follow-up of the disease are discussed. The world increase of serious streptococcal infections in the last 10 years, probably will become neonatal Streptococcus pyogenes meningitis more frequent in the future and it is important to be alert for the precocious diagnosis and the possible complications of that potentially lethal infection. PMID:10029890

  10. Changes in Streptococcus pyogenes causing invasive disease in Portugal: evidence for superantigen gene loss and acquisition.

    PubMed

    Friães, Ana; Lopes, Joana P; Melo-Cristino, José; Ramirez, Mario

    2013-12-01

    The emergence of highly virulent and successful Streptococcus pyogenes (group A streptococci - GAS) clones has been attributed to the exchange of virulence factors by lateral gene transfer mechanisms, which strongly contribute to genomic diversity. We characterized a collection of 191 GAS isolates recovered from normally sterile sites in Portugal during 2006-2009 and compared them to invasive isolates obtained during 2000-2005. Antimicrobial resistance rates did not change significantly between the two periods and were generally low. In 2006-2009, emm1, emm89, emm3, and emm6 represented 60% of the isolates. The chromosomally encoded superantigen (SAg) genes speG and smeZ were present in the majority (>90%) of the isolates, while speJ was found in only 45%. The phage encoded SAgs varied greatly in prevalence (2-53%). The distribution of emm types, pulsed-field gel electrophoresis profiling (PFGE) clusters, and SAg profiles changed significantly between the periods, although there were no statistically supported changes in the prevalence of individual types. While the macrolide susceptible clone emm1-T1-ST28 remained dominant (28%), there was a significant decrease in clonal diversity as indicated by both PFGE profiling and emm typing. This was accompanied by intra-clonal divergence of SAg profiles, which was statistically confirmed for isolates representing emm1, emm28, and emm44. This diversification was associated with the loss and acquisition of SAg genes, carried by phages and of chromosomal origin. These data suggest an ongoing genomic diversification of GAS invasive isolates in Portugal that may contribute to the persistence of clones with improved fitness or virulence. PMID:23932912

  11. [Epidemiology of Streptococcus pyogenes invasive diseases in France (2007-2011)].

    PubMed

    Plainvert, C; Loubinoux, J; Bidet, P; Doloy, A; Touak, G; Dmytruk, N; Collobert, G; Bingen, E; Bouvet, A; Fouet, A; Poyart, C

    2014-11-01

    Group A Streptococcus (GAS) is a human pathogen responsible for a wide range of clinical manifestations. An increase of GAS invasive infections has been described since the mid 1980s. To study the French epidemiology of invasive infections (i) we characterized all GAS invasive strains received at the French National Reference Center for streptococci (CNR-Strep) between 2007 and 2011; (ii) we analyzed the epidemiological data on the corresponding strains. For each strain, emm genotype, superantigen genes and antibiotics susceptibility were determined. Among the 2 603 non redundant invasive GAS strains, 65.1 % (n=1 695) were isolated from blood culture. A streptococcal toxic shock syndrome (STSS) was described in 16.4 % (n=428) of cases, mostly associated with necrotizing fasciitis (NF), pleuropulmonary or osteoarticular infections (p ≤0.001). The case fatality rate was 10.6 %. A total of 102 different emm genotypes were identified. Three emm genotypes predominated, reaching nearly 60 % of the strains: emm 1 (26.7 %), emm 28 (16.4 %), and emm 89 (12.8 %). The proportion of each emm genotype varied according to the year and the age of patients. Among those < 15 years old, the three main genotypes were emm 1 (36.8 %), emm 12 (12.9 %) and emm 4 (9.5 %). The distribution of superantigen genes (SpeA, SpeC and Ssa) was restricted to several emm genotypes. Between 2007 and 2011, the rate of macrolides resistant GAS strains decreased from 7.8 to 5.5 %. emm 1 strains are still the most common especially in most severe clinical manifestations including STSS and NF. PMID:25456682

  12. Thermoregulation of Capsule Production by Streptococcus pyogenes

    PubMed Central

    Kang, Song Ok; Wright, Jordan O.; Tesorero, Rafael A.; Lee, Hyunwoo; Beall, Bernard; Cho, Kyu Hong

    2012-01-01

    The capsule of Streptococcus pyogenes serves as an adhesin as well as an anti-phagocytic factor by binding to CD44 on keratinocytes of the pharyngeal mucosa and the skin, the main entry sites of the pathogen. We discovered that S. pyogenes HSC5 and MGAS315 strains are further thermoregulated for capsule production at a post-transcriptional level in addition to the transcriptional regulation by the CovRS two-component regulatory system. When the transcription of the hasABC capsular biosynthetic locus was de-repressed through mutation of the covRS system, the two strains, which have been used for pathogenesis studies in the laboratory, exhibited markedly increased capsule production at sub-body temperature. Employing transposon mutagenesis, we found that CvfA, a previously identified membrane-associated endoribonuclease, is required for the thermoregulation of capsule synthesis. The mutation of the cvfA gene conferred increased capsule production regardless of temperature. However, the amount of the capsule transcript was not changed by the mutation, indicating that a post-transcriptional regulator mediates between CvfA and thermoregulated capsule production. When we tested naturally occurring invasive mucoid strains, a high percentage (11/53, 21%) of the strains exhibited thermoregulated capsule production. As expected, the mucoid phenotype of these strains at sub-body temperature was due to mutations within the chromosomal covRS genes. Capsule thermoregulation that exhibits high capsule production at lower temperatures that occur on the skin or mucosal surface potentially confers better capability of adhesion and invasion when S. pyogenes penetrates the epithelial surface. PMID:22615992

  13. Clinical and microbial characteristics of invasive Streptococcus pyogenes disease in New Caledonia, a region in Oceania with a high incidence of acute rheumatic fever.

    PubMed

    Le Hello, S; Doloy, A; Baumann, F; Roques, N; Coudene, P; Rouchon, B; Lacassin, F; Bouvet, A

    2010-02-01

    New Caledonia is an archipelago in the South Pacific with a high prevalence of acute rheumatic fever and rheumatic heart disease. Conducted in 2006, this study aimed at characterizing clinical manifestations and microbial features of isolates obtained from invasive Streptococcus pyogenes disease. Clinical and demographic data were collected prospectively. Isolates were biotyped, T typed, emm sequenced, and tested for antibiotic susceptibility. Detection of the speA, speB, speC, and ssa genes was also carried out. The estimated annual incidence of invasive S. pyogenes disease in 2006 was high at 38 cases/100,000 inhabitants in New Caledonia. Invasive isolates were obtained from 90 patients with necrotizing fasciitis (41 cases), bacteremia with no identified focus (12 cases), myositis (10 cases), septic arthritis (9 cases), erysipelas (8 cases), postpartum infection (4 cases), myelitis and osteomyelitis (3 cases), severe pneumonia (2 cases), and endocarditis (1 case). The most frequent associated comorbidities were skin lesions (71%) and obesity (29%). Thirty-one different emm types were identified, and the following six accounted for 54% of the isolates: emm15 (15.5%), emm92 (12.2%), emm106 (8.9%), emm74 (6.7%), emm89 (5.6%), and emm109 (5.6%). The speA, speC, and ssa genes were expressed at different frequencies in the various emm types. The first epidemiological study of invasive S. pyogenes disease in New Caledonia highlights that emm type distribution is particular and should be taken into account in the development of an appropriate vaccine. These findings support the prevention of pyoderma and other cutaneous lesions in order to limit the development of both invasive disease and poststreptococcal sequelae in the South Pacific. PMID:19955276

  14. Invasive Streptococcus pyogenes after allograft implantation--Colorado, 2003.

    PubMed

    2003-12-01

    Allograft tissues are used for various orthopedic procedures (e.g., ligament reconstruction, meniscal transplantation, and spinal surgery). In 2002, approximately one million allografts were distributed for transplantation (American Association of Tissue Banks [AATB], unpublished data, 2002). Recent reports of allograft-associated infections have prompted evaluation of the processing and quality-control methods employed by tissue processors. This report describes a case of invasive disease with Streptococcus pyogenes (i.e., group A streptococcus [GAS]), after reconstructive knee surgery using contaminated allograft tissue and provides recommendations to reduce the risk for allograft-associated infections. Although allograft infections are rare, they highlight the need for improved tissue evaluation and processing standards. PMID:14654764

  15. [Invasive disease due to Streptococcus pyogenes in a patient with A H1N1 influenza infection. Report of one case].

    PubMed

    Guerrero S, Gonzalo; Marín S, Felipe

    2015-08-01

    Bacterial superinfection is a known complication among patients affected by viral respiratory tract infections. Streptococcus pyogenes, a major bacterial agent involved in acute tonsillopharyngitis, skin and soft tissue infections, was reported as a co-infecting microorganism during the 2009 A H1N1 influenza pandemic. We report a 65-year-old male patient who evolved with multifocal pneumonia and multiple organ failure with a fatal outcome. Influenza A H1N1 was detected by a polymerase chain reaction-based technique from a tracheal aspirate sample. S. pyogenes was identified by a rapid test from a nasopharyngeal sample and isolated afterwards from a positive blood culture. PMID:26436938

  16. Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus: S. pyogenes super-infection.

    PubMed

    Klonoski, Joshua M; Hurtig, Heather R; Juber, Brian A; Schuneman, Margaret J; Bickett, Thomas E; Svendsen, Joshua M; Burum, Brandon; Penfound, Thomas A; Sereda, Grigoriy; Dale, James B; Chaussee, Michael S; Huber, Victor C

    2014-09-01

    Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The ?-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection. PMID:25077423

  17. Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole?

    PubMed

    Bowen, Asha C; Lilliebridge, Rachael A; Tong, Steven Y C; Baird, Robert W; Ward, Peter; McDonald, Malcolm I; Currie, Bart J; Carapetis, Jonathan R

    2012-12-01

    Streptococcus pyogenes is commonly believed to be resistant to trimethoprim-sulfamethoxazole (SXT), resulting in reservations about using SXT for skin and soft tissue infections (SSTI) where S. pyogenes is involved. S. pyogenes' in vitro susceptibility to SXT depends on the medium's thymidine content. Thymidine allows S. pyogenes to bypass the sulfur-mediated inhibition of folate metabolism and, historically, has resulted in apparently reduced susceptibility of S. pyogenes to sulfur antibacterials. The low thymidine concentration in Mueller-Hinton agar (MHA) is now regulated. We explored S. pyogenes susceptibility to SXT on various media. Using two sets of 100 clinical S. pyogenes isolates, we tested for susceptibility using SXT Etests on MHA containing defibrinated horse blood and 20 mg/liter ?-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA). European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints defined susceptibility (MIC, ? 1 mg/liter) and resistance (MIC, >2 mg/liter). In study 1, 99% of S. pyogenes isolates were susceptible to SXT on MHA, MHBA, and MHLHBA, with geometric mean MICs of 0.04, 0.04, and 0.05 mg/liter, respectively. In study 2, all 100 S. pyogenes isolates were susceptible to SXT on MHF, MHS, MHA, and MHLHBA with geometric mean MICs of 0.07, 0.16, 0.07, and 0.09 mg/liter, respectively. This study confirms the in vitro susceptibility of S. pyogenes to SXT, providing support for the use of SXT for SSTIs. A clinical trial using SXT for impetigo is ongoing. PMID:23052313

  18. Molecular Epidemiology of sil Locus in Clinical Streptococcus pyogenes Strains

    PubMed Central

    Plainvert, Cline; Dinis, Mrcia; Ravins, Miriam; Hanski, Emanuel; Touak, Grald; Dmytruk, Nicolas; Fouet, Agns

    2014-01-01

    Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide variety of diseases, ranging from mild noninvasive to severe invasive infections. Mutations in regulatory components have been implicated in the switch from colonization to invasive phenotypes. The inactivation of the sil locus, composed of six genes encoding a quorum-sensing complex, gives rise to a highly invasive strain. However, studies conducted on limited collections of GAS strains suggested that sil prevalence is around 15%; furthermore, whereas a correlation between the presence of sil and the genetic background was suggested, no link between the presence of a functional sil locus and the invasive status was assessed. We established a collection of 637 nonredundant strains covering all emm genotypes present in France and of known clinical history; 68%, 22%, and 10% were from invasive infections, noninvasive infections, and asymptomatic carriage, respectively. Among the 637 strains, 206 were sil positive. The prevalence of the sil locus varied according to the emm genotype, being present in >85% of the emm4, emm18, emm32, emm60, emm87, and emm90 strains and absent from all emm1, emm28, and emm89 strains. A random selection based on 2009 French epidemiological data indicated that 16% of GAS strains are sil positive. Moreover, due to mutations leading to truncated proteins, only 9% of GAS strains harbor a predicted functional sil system. No correlation was observed between the presence or absence of a functional sil locus and the strain invasiveness status. PMID:24671796

  19. Molecular epidemiology of sil locus in clinical Streptococcus pyogenes strains.

    PubMed

    Plainvert, Cline; Dinis, Mrcia; Ravins, Miriam; Hanski, Emanuel; Touak, Grald; Dmytruk, Nicolas; Fouet, Agns; Poyart, Claire

    2014-06-01

    Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide variety of diseases, ranging from mild noninvasive to severe invasive infections. Mutations in regulatory components have been implicated in the switch from colonization to invasive phenotypes. The inactivation of the sil locus, composed of six genes encoding a quorum-sensing complex, gives rise to a highly invasive strain. However, studies conducted on limited collections of GAS strains suggested that sil prevalence is around 15%; furthermore, whereas a correlation between the presence of sil and the genetic background was suggested, no link between the presence of a functional sil locus and the invasive status was assessed. We established a collection of 637 nonredundant strains covering all emm genotypes present in France and of known clinical history; 68%, 22%, and 10% were from invasive infections, noninvasive infections, and asymptomatic carriage, respectively. Among the 637 strains, 206 were sil positive. The prevalence of the sil locus varied according to the emm genotype, being present in >85% of the emm4, emm18, emm32, emm60, emm87, and emm90 strains and absent from all emm1, emm28, and emm89 strains. A random selection based on 2009 French epidemiological data indicated that 16% of GAS strains are sil positive. Moreover, due to mutations leading to truncated proteins, only 9% of GAS strains harbor a predicted functional sil system. No correlation was observed between the presence or absence of a functional sil locus and the strain invasiveness status. PMID:24671796

  20. The role of coagulation/fibrinolysis during Streptococcus pyogenes infection

    PubMed Central

    Loof, Torsten G.; Deicke, Christin; Medina, Eva

    2014-01-01

    The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit. PMID:25309880

  1. The role of coagulation/fibrinolysis during Streptococcus pyogenes infection.

    PubMed

    Loof, Torsten G; Deicke, Christin; Medina, Eva

    2014-01-01

    The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit. PMID:25309880

  2. In Vitro Antibacterial Activity of Essential Oils against Streptococcus pyogenes.

    PubMed

    Sfeir, Julien; Lefranois, Corinne; Baudoux, Dominique; Derbr, Sverine; Licznar, Patricia

    2013-01-01

    Streptococcus pyogenes plays an important role in the pathogenesis of tonsillitis. The present study was conducted to evaluate the in vitro antibacterial activities of 18 essential oils chemotypes from aromatic medicinal plants against S. pyogenes. Antibacterial activity of essential oils was investigated using disc diffusion method. Minimum Inhibitory Concentration of essential oils showing an important antibacterial activity was measured using broth dilution method. Out of 18 essential oils tested, 14 showed antibacterial activity against S. pyogenes. Among them Cinnamomum verum, Cymbopogon citratus, Thymus vulgaris CT thymol, Origanum compactum, and Satureja montana essential oils exhibited significant antibacterial activity. The in vitro results reported here suggest that, for patients suffering from bacterial throat infections, if aromatherapy is used, these essential oils, considered as potential antimicrobial agents, should be preferred. PMID:23662123

  3. Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG

    PubMed Central

    Reglinski, Mark; Lynskey, Nicola N.; Choi, Yoon Jung; Edwards, Robert J.; Sriskandan, Shiranee

    2016-01-01

    Summary Objectives Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. Methods Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. Results Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. Conclusion Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. PMID:26880087

  4. Streptococcus pyogenes biofilms—formation, biology, and clinical relevance

    PubMed Central

    Fiedler, Tomas; Köller, Thomas; Kreikemeyer, Bernd

    2015-01-01

    Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options. PMID:25717441

  5. Delineation of Streptococcus dysgalactiae, Its Subspecies, and Its Clinical and Phylogenetic Relationship to Streptococcus pyogenes

    PubMed Central

    Jensen, Anders

    2012-01-01

    The taxonomic status and structure of Streptococcus dysgalactiae have been the object of much confusion. Bacteria belonging to this species are usually referred to as Lancefield group C or group G streptococci in clinical settings in spite of the fact that these terms lack precision and prevent recognition of the exact clinical relevance of these bacteria. The purpose of this study was to develop an improved basis for delineation and identification of the individual species of the pyogenic group of streptococci in the clinical microbiology laboratory, with a special focus on S. dysgalactiae. We critically reexamined the genetic relationships of the species S. dysgalactiae, Streptococcus pyogenes, Streptococcus canis, and Streptococcus equi, which may share Lancefield group antigens, by phylogenetic reconstruction based on multilocus sequence analysis (MLSA) and 16S rRNA gene sequences and by emm typing combined with phenotypic characterization. Analysis of concatenated sequences of seven genes previously used for examination of viridans streptococci distinguished robust and coherent clusters. S. dysgalactiae consists of two separate clusters consistent with the two recognized subspecies dysgalactiae and equisimilis. Both taxa share alleles with S. pyogenes in several housekeeping genes, which invalidates identification based on single-locus sequencing. S. dysgalactiae, S. canis, and S. pyogenes constitute a closely related branch within the genus Streptococcus indicative of recent descent from a common ancestor, while S. equi is highly divergent from other species of the pyogenic group streptococci. The results provide an improved basis for identification of clinically important pyogenic group streptococci and explain the overlapping spectrum of infections caused by the species associated with humans. PMID:22075580

  6. Streptococcus pyogenes Infection in a Free-Living European Hedgehog (Erinaceus europaeus).

    PubMed

    Franklinos, Lydia H V; Efstratiou, Androulla; Macgregor, Shaheed K; John, Shinto K; Hopkins, Timothy; Cunningham, Andrew A; Lawson, Becki

    2015-12-01

    Streptococcus pyogenes, a common pathogen of humans, was isolated from the carcass of a free-living European hedgehog (Erinaceus europaeus) found in northern England in June 2014. The animal had abscessation of the deep right cervical lymph node, mesenteric lymph nodes and liver. The S. pyogenes strain isolated from the lesions, peritoneal and pleural cavities was characterised as emm 28, which can be associated with invasive disease in humans. This is the first known report of S. pyogenes in a hedgehog and in any free-living wild animal that has been confirmed by gene sequencing. As close associations between wild hedgehogs and people in England are common, we hypothesise that this case might have resulted from anthroponotic infection. PMID:26242215

  7. Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and methicillin-resistant Staphylococcus aureus.

    PubMed

    Gilmer, Daniel B; Schmitz, Jonathan E; Euler, Chad W; Fischetti, Vincent A

    2013-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococcus [GrAS]) cause serious and sometimes fatal human diseases. They are among the many Gram-positive pathogens for which resistance to leading antibiotics has emerged. As a result, alternative therapies need to be developed to combat these pathogens. We have identified a novel bacteriophage lysin (PlySs2), derived from a Streptococcus suis phage, with broad lytic activity against MRSA, vancomycin-intermediate S. aureus (VISA), Streptococcus suis, Listeria, Staphylococcus simulans, Staphylococcus epidermidis, Streptococcus equi, Streptococcus agalactiae (group B streptococcus [GBS]), S. pyogenes, Streptococcus sanguinis, group G streptococci (GGS), group E streptococci (GES), and Streptococcus pneumoniae. PlySs2 has an N-terminal cysteine-histidine aminopeptidase (CHAP) catalytic domain and a C-terminal SH3b binding domain. It is stable at 50 °C for 30 min, 37 °C for >24 h, 4°C for 15 days, and -80 °C for >7 months; it maintained full activity after 10 freeze-thaw cycles. PlySs2 at 128 μg/ml in vitro reduced MRSA and S. pyogenes growth by 5 logs and 3 logs within 1 h, respectively, and exhibited a MIC of 16 μg/ml for MRSA. A single, 2-mg dose of PlySs2 protected 92% (22/24) of the mice in a bacteremia model of mixed MRSA and S. pyogenes infection. Serially increasing exposure of MRSA and S. pyogenes to PlySs2 or mupirocin resulted in no observed resistance to PlySs2 and resistance to mupirocin. To date, no other lysin has shown such notable broad lytic activity, stability, and efficacy against multiple, leading, human bacterial pathogens; as such, PlySs2 has all the characteristics to be an effective therapeutic. PMID:23571534

  8. Novel Bacteriophage Lysin with Broad Lytic Activity Protects against Mixed Infection by Streptococcus pyogenes and Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Gilmer, Daniel B.; Schmitz, Jonathan E.; Euler, Chad W.

    2013-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A streptococcus [GrAS]) cause serious and sometimes fatal human diseases. They are among the many Gram-positive pathogens for which resistance to leading antibiotics has emerged. As a result, alternative therapies need to be developed to combat these pathogens. We have identified a novel bacteriophage lysin (PlySs2), derived from a Streptococcus suis phage, with broad lytic activity against MRSA, vancomycin-intermediate S. aureus (VISA), Streptococcus suis, Listeria, Staphylococcus simulans, Staphylococcus epidermidis, Streptococcus equi, Streptococcus agalactiae (group B streptococcus [GBS]), S. pyogenes, Streptococcus sanguinis, group G streptococci (GGS), group E streptococci (GES), and Streptococcus pneumoniae. PlySs2 has an N-terminal cysteine-histidine aminopeptidase (CHAP) catalytic domain and a C-terminal SH3b binding domain. It is stable at 50°C for 30 min, 37°C for >24 h, 4°C for 15 days, and −80°C for >7 months; it maintained full activity after 10 freeze-thaw cycles. PlySs2 at 128 μg/ml in vitro reduced MRSA and S. pyogenes growth by 5 logs and 3 logs within 1 h, respectively, and exhibited a MIC of 16 μg/ml for MRSA. A single, 2-mg dose of PlySs2 protected 92% (22/24) of the mice in a bacteremia model of mixed MRSA and S. pyogenes infection. Serially increasing exposure of MRSA and S. pyogenes to PlySs2 or mupirocin resulted in no observed resistance to PlySs2 and resistance to mupirocin. To date, no other lysin has shown such notable broad lytic activity, stability, and efficacy against multiple, leading, human bacterial pathogens; as such, PlySs2 has all the characteristics to be an effective therapeutic. PMID:23571534

  9. Cationic Antimicrobial Peptides Disrupt the Streptococcus pyogenes ExPortal

    PubMed Central

    Vega, Luis Alberto; Caparon, Michael G.

    2012-01-01

    Summary Although they possess a well-characterized ability to porate the bacterial membrane, emerging research suggests that cationic antimicrobial peptides (CAPs) can influence pathogen behavior at levels that are sub-lethal. In this study, we investigated the interaction of polymyxin B and human neutrophil peptide (HNP-1) with the human pathogen Streptococcus pyogenes. At sub-lethal concentrations, these CAPs preferentially targeted the ExPortal, a unique microdomain of the S. pyogenes membrane, specialized for protein secretion and processing. A consequence of this interaction was the disruption of ExPortal organization and a redistribution of ExPortal components into the peripheral membrane. Redistribution was associated with inhibition of secretion of certain toxins, including the SpeB cysteine protease and the Streptolysin O (SLO) cytolysin, but not SIC, a protein that protects S. pyogenes from CAPs. These data suggest a novel function for CAPs in targeting the ExPortal and interfering with secretion of factors required for infection and survival. This mechanism may prove valuable for the design of new types of antimicrobial agents to combat the emergence of antibiotic-resistant pathogens. PMID:22780862

  10. RNA sequencing uncovers antisense RNAs and novel small RNAs in Streptococcus pyogenes.

    PubMed

    Le Rhun, Anas; Beer, Yan Yan; Reimegrd, Johan; Chylinski, Krzysztof; Charpentier, Emmanuelle

    2016-02-01

    Streptococcus pyogenes is a human pathogen responsible for a wide spectrum of diseases ranging from mild to life-threatening infections. During the infectious process, the temporal and spatial expression of pathogenicity factors is tightly controlled by a complex network of protein and RNA regulators acting in response to various environmental signals. Here, we focus on the class of small RNA regulators (sRNAs) and present the first complete analysis of sRNA sequencing data in S. pyogenes. In the SF370 clinical isolate (M1 serotype), we identified 197 and 428 putative regulatory RNAs by visual inspection and bioinformatics screening of the sequencing data, respectively. Only 35 from the 197 candidates identified by visual screening were assigned a predicted function (T-boxes, ribosomal protein leaders, characterized riboswitches or sRNAs), indicating how little is known about sRNA regulation in S. pyogenes. By comparing our list of predicted sRNAs with previous S. pyogenes sRNA screens using bioinformatics or microarrays, 92 novel sRNAs were revealed, including antisense RNAs that are for the first time shown to be expressed in this pathogen. We experimentally validated the expression of 30 novel sRNAs and antisense RNAs. We show that the expression profile of 9 sRNAs including 2 predicted regulatory elements is affected by the endoribonucleases RNase III and/or RNase Y, highlighting the critical role of these enzymes in sRNA regulation. PMID:26580233

  11. Platelet-Dependent Neutrophil Function Is Dysregulated by M Protein from Streptococcus pyogenes.

    PubMed

    Hurley, Sinéad M; Kahn, Fredrik; Nordenfelt, Pontus; Mörgelin, Matthias; Sørensen, Ole E; Shannon, Oonagh

    2015-09-01

    Platelets are rapidly responsive sentinel cells that patrol the bloodstream and contribute to the host response to infection. Platelets have been reported to form heterotypic aggregates with leukocytes and may modulate their function. Here, we have investigated platelet-neutrophil complex formation and neutrophil function in response to distinct agonists. The endogenous platelet activator thrombin gave rise to platelet-dependent neutrophil activation, resulting in enhanced phagocytosis and bacterial killing. Streptococcus pyogenes is an important causative agent of severe infectious disease, which can manifest as sepsis and septic shock. M1 protein from S. pyogenes also mediated platelet-neutrophil complex formation; however, these neutrophils were dysfunctional and exhibited diminished chemotactic ability and bacterial killing. This reveals an important agonist-dependent neutrophil dysfunction during platelet-neutrophil complex formation and highlights the role of platelets during the immune response to streptococcal infection. PMID:26099589

  12. Murine Vaginal Colonization Model for Investigating Asymptomatic Mucosal Carriage of Streptococcus pyogenes

    PubMed Central

    Watson, Michael E.; Nielsen, Hailyn V.; Hultgren, Scott J.

    2013-01-01

    While many virulence factors promoting Streptococcus pyogenes invasive disease have been described, specific streptococcal factors and host properties influencing asymptomatic mucosal carriage remain uncertain. To address the need for a refined model of prolonged S. pyogenes asymptomatic mucosal colonization, we have adapted a preestrogenized murine vaginal colonization model for S. pyogenes. In this model, derivatives of strains HSC5, SF370, JRS4, NZ131, and MEW123 established a reproducible, asymptomatic colonization of the vaginal mucosa over a period of typically 3 to 4 weeks' duration at a relatively high colonization efficiency. Prior treatment with estradiol prolonged streptococcal colonization and was associated with reduced inflammation in the colonized vaginal epithelium as well as a decreased leukocyte presence in vaginal fluid compared to the levels of inflammation and leukocyte presence in non-estradiol-treated control mice. The utility of our model for investigating S. pyogenes factors contributing to mucosal carriage was verified, as a mutant with a mutation in the transcriptional regulator catabolite control protein A (CcpA) demonstrated significant impairment in vaginal colonization. An assessment of in vivo transcriptional activity in the CcpA? strain for several known CcpA-regulated genes identified significantly elevated transcription of lactate oxidase (lctO) correlating with excessive generation of hydrogen peroxide to self-lethal levels. Deletion of lctO did not impair colonization, but deletion of lctO in a CcpA? strain prolonged carriage, exceeding even that of the wild-type strain. Thus, while LctO is not essential for vaginal colonization, its dysregulation is deleterious, highlighting the critical role of CcpA in promoting mucosal colonization. The vaginal colonization model should prove effective for future analyses of S. pyogenes mucosal colonization. PMID:23460515

  13. Detection of early gastric cancer facilitated by surveillance for a pyogenic liver abscess caused by Streptococcus intermedius.

    PubMed

    Shigefuku, Ryuta; Matsunaga, Kotaro; Tamura, Tomohiro; Ozawa, Shun-Ichiro; Matsuo, Yasumasa; Takahashi, Hideaki; Matsumoto, Nobuyuki; Okuse, Chiaki; Suzuki, Michihiro; Itoh, Fumio

    2016-01-01

    We report a case of early gastric cancer that was detected during surveillance of a pyogenic liver abscess caused by Streptococcus intermedius, an oral microbiota. Treatment with proton pump inhibitors can result in the alteration of gastric bacterial flora by altering intragastric acidity. This can place immunocompromised patients, such as those with diabetes mellitus and the elderly, at an increased risk for disease of the upper gastrointestinal tract to be a route of bacterial transmission. In this case, the patient developed a pyogenic liver abscess. PMID:26853986

  14. Targeted Curing of All Lysogenic Bacteriophage from Streptococcus pyogenes Using a Novel Counter-selection Technique

    PubMed Central

    Euler, Chad W.; Juncosa, Barbara; Ryan, Patricia A.; Deutsch, Douglas R.; McShan, W. Michael; Fischetti, Vincent A.

    2016-01-01

    Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR) and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS), into a targeted prophage on the chromosome of a streptomycin resistant (SmR) mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome); the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S. pyogenes and further elucidate how the presence of prophage may affect overall streptococcal survival, pathogenicity, and evolution. PMID:26756207

  15. Targeted Curing of All Lysogenic Bacteriophage from Streptococcus pyogenes Using a Novel Counter-selection Technique.

    PubMed

    Euler, Chad W; Juncosa, Barbara; Ryan, Patricia A; Deutsch, Douglas R; McShan, W Michael; Fischetti, Vincent A

    2016-01-01

    Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR) and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS), into a targeted prophage on the chromosome of a streptomycin resistant (SmR) mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome); the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S. pyogenes and further elucidate how the presence of prophage may affect overall streptococcal survival, pathogenicity, and evolution. PMID:26756207

  16. Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes

    PubMed Central

    Ong, Cheryl-lynn Y.; Walker, Mark J.; McEwan, Alastair G.

    2015-01-01

    Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways. PMID:26028191

  17. Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.

    PubMed

    Ong, Cheryl-lynn Y; Walker, Mark J; McEwan, Alastair G

    2015-01-01

    Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways. PMID:26028191

  18. Epidemiology of necrotizing infection caused by Staphylococcus aureus and Streptococcus pyogenes at an Iowa hospital.

    PubMed

    Thapaliya, Dipendra; O'Brien, Ashley M; Wardyn, Shylo E; Smith, Tara C

    2015-01-01

    The present study was performed to characterize the epidemiology of necrotizing soft tissue infection caused by Streptococcus pyogenes (n=14) and Staphylococcus aureus (n=14) isolates collected at the University of Iowa Hospitals and Clinics. An additional 9 S. pyogenes isolates were collected from patients being treated for mild respiratory infections and served as a comparison sample in the analysis. Patient data corresponding to the isolates (n=37) were also collected in order to identify risk factors or comorbid conditions possibly correlated with necrotizing fasciitis (NF). The prevalence of methicillin-resistant S. aureus among the study isolates was 35.7% (5/14), and the prevalence of the Panton-Valentine leukocidin (PVL) gene was 57% (8/14). The S. pyogenes NF (wound) isolates (n=14) belonged to 10 different emm types, none of which appeared to be associated with more severe disease when compared to the milder infection (throat) samples (n=9). Comorbid conditions such as diabetes and cardiovascular disease were significantly associated with NF. The results indicate that there may be a high prevalence of the PVL virulence factor in NF infections and that spa type t008 may be responsible for the increasing incidence of S. aureus NF infections in Iowa. PMID:26163423

  19. Characterization of an erythromycin resistance (erm) plasmid in Streptococcus pyogenes.

    PubMed

    Schaln, C; Gebreselassie, D; Sthl, S

    1995-01-01

    Three erythromyxin-resistant Swedish isolates of Streptococcus pyogenes, representing different T-types, were studied. Two of the strains showed constitutive high-level (MIC > 200 micrograms/ml) and one showed moderate (MIC 6.4 micrograms/ml) resistance; the latter strain was sensitive to lincosamide and clindamycin, and resistance was not induced by erythromycin. In each of the strains, a plasmid with an estimated Mw of 17.6 +/- 0.9 x 10(6) was isolated in addition to smaller cryptic plasmids. The three plasmids pSE701, pSE702, and pSE703 had very similar restriction enzyme cleavage patterns. Novobiocin curing of the high-level resistance strain ER559 showed the resistance to be linked to its 17.6 x 10(6) plasmid, pSE703. Furthermore, by electroporation this rather large plasmid was reintroduced into an erythromycin-sensitive cured derivative, acquiring resistance, and the plasmid was again recovered from the transconjugant. One of the plasmids, pSE702, was shown by filter mating to be conjugative within S. pyogenes. DNA-DNA hybridization showed that the resistance determinant of the present three isolates was related to the erm gene on plasmid pAM beta 1 of Enterococcus faecalis but not to that of plasmid pE194 of Staphylococcus aureus. The copy numbers of pSE702 and pSE703, derived from the two high-level resistant strains, were 11 +/- 3 and 17 +/- 5 compared to 2 +/- 1 for pSE701, derived from the moderately resistant strain, possibly accounting for the phenotypic variation observed. The plasmids pSE702 and pAM beta 1 showed about 80% homology in DNA-DNA hybridization tests and high similarity in their restriction maps. PMID:7695892

  20. In Silico Investigation for Evaluation of the Potential of the SclA Protein in Streptococcus pyogenes

    PubMed Central

    Pourhajibagher, Maryam; Bahador, Abbas

    2015-01-01

    Background: Streptococcus pyogenes is an important pathogen that is associated with a range of infections in humans, and causes common and severe invasive diseases. Currently, antimicrobial therapy is the first choice for the treatment of S. pyogenes; however, the emergence of antimicrobial resistance and side effects of antibacterial drugs is increasing. Consequently, there is an increased demand for novel drug targets and vaccine design. Objectives: To develop an effective vaccine against Streptococcus pyogenes (group A streptococcus) , we described a novel collagen-like surface protein of S. pyogenes which is important virulence factors Materials and Methods: In this study, we focused on the SclA protein of S. pyogenes and characterized it using bioinformatic tools to introduce it as a candidate novel drug as a candidate for use in vaccine design. The secondary structure was determined and the 3D structure was modeled using SWISS-MODEL workspace. The immune epitope database analysis (IEDB) resource was used to predict regions of SclA that are likely to be recognized as epitopes. Results: The SclA protein is present on the cell surface of the cell and has interact with a common ligand by its hypervariable NH2-terminal regions. The IEDB showed that the maximum peptide length that is likely to be predicted as an epitope is of 6 amino acids, from amino acid 26 to 31, with a score of 4.791. This epitope can be considered for use in Antibody and drug design. Conclusions: Data from this study about SclA were not sufficient and further studies are needed; however, the information here suggests that SclA could be a candidate for further research on the design of drugs and vaccines against S. pyogenes infections. PMID:26495104

  1. CodY-mediated regulation of Streptococcus pyogenes exoproteins

    PubMed Central

    2012-01-01

    Background The production of Streptococcus pyogenes exoproteins, many of which contribute to virulence, is regulated in response to nutrient availability. CodY is a transcriptional regulator that controls gene expression in response to amino acid availability. The purpose of this study was to identify differences in the expression of streptococcal exoproteins associated with deletion of the codY gene. Results We compared the secreted proteins produced by wild-type S. pyogenes to a codY mutant in the post-exponential phase of growth. We used both one and two-dimensional gel electrophoresis to separate exoproteins. Proteins that were significantly different in abundance upon repeated analysis were identified with tandem mass spectrometry. The production of the secreted cysteine protease SpeB, a secreted chromosomally encoded nuclease (SdaB), and a putative adhesion factor (Spy49_0549) were more abundant in supernatant fluids obtained from the codY mutant. In addition, hyaluronidase (HylA), CAMP factor (Cfa), a prophage encoded nuclease (Spd-3), and an uncharacterized extracellular protein (Spy49_0015) were less abundant in supernatant fluids obtained from the codY mutant strain. Enzymatic assays showed greater DNase activity in culture supernatants isolated in the post-exponential phase of growth from the codY mutant strain compared to the wild-type strain. Because extracellular nucleases and proteases can influence biofilm formation, we also measured the ability of the strains to form biofilms during growth with both rich medium (Todd Hewitt yeast extract; THY) and chemically defined media (CDM). No difference was observed with rich media but with CDM the biofilms formed by the codY mutant strain had less biomass compared to the wild-type strain. Conclusions Overall, the results indicate that CodY alters the abundance of a select group of S. pyogenes exoproteins, including DNases, a protease, and hylauronidase, which together may alleviate starvation by promoting dissemination of the pathogen to nutrient rich environments and by hydrolysis of host macromolecules. PMID:22721528

  2. Streptococcal 5'-Nucleotidase A (S5nA), a Novel Streptococcus pyogenes Virulence Factor That Facilitates Immune Evasion.

    PubMed

    Zheng, Lisa; Khemlani, Adrina; Lorenz, Natalie; Loh, Jacelyn M S; Langley, Ries J; Proft, Thomas

    2015-12-25

    Streptococcus pyogenes is an important human pathogen that causes a wide range of diseases. Using bioinformatics analysis of the complete S. pyogenes strain SF370 genome, we have identified a novel S. pyogenes virulence factor, which we termed streptococcal 5'-nucleotidase A (S5nA). A recombinant form of S5nA hydrolyzed AMP and ADP, but not ATP, to generate the immunomodulatory molecule adenosine. Michaelis-Menten kinetics revealed a Km of 169 ?m and a Vmax of 7550 nmol/mg/min for the substrate AMP. Furthermore, recombinant S5nA acted synergistically with S. pyogenes nuclease A to generate macrophage-toxic deoxyadenosine from DNA. The enzyme showed optimal activity between pH 5 and pH 6.5 and between 37 and 47 C. Like other 5'-nucleotidases, S5nA requires divalent cations and was active in the presence of Mg(2+), Ca(2+), or Mn(2+). However, Zn(2+) inhibited the enzymatic activity. Structural modeling combined with mutational analysis revealed a highly conserved catalytic dyad as well as conserved substrate and cation-binding sites. Recombinant S5nA significantly increased the survival of the non-pathogenic bacterium Lactococcus lactis during a human whole blood killing assay in a dose-dependent manner, suggesting a role as an S. pyogenes virulence factor. In conclusion, we have identified a novel S. pyogenes enzyme with 5'-nucleotidase activity and immune evasion properties. PMID:26527680

  3. Streptococcus pyogenes and re-emergence of scarlet fever as a public health problem

    PubMed Central

    Wong, Samson SY; Yuen, Kwok-Yung

    2012-01-01

    Explosive outbreaks of infectious diseases occasionally occur without immediately obvious epidemiological or microbiological explanations. Plague, cholera and Streptococcus pyogenes infection are some of the epidemic-prone bacterial infections. Besides epidemiological and conventional microbiological methods, the next-generation gene sequencing technology permits prompt detection of genomic and transcriptomic profiles associated with invasive phenotypes. Horizontal gene transfer due to mobile genetic elements carrying virulence factors and antimicrobial resistance, or mutations associated with the two component CovRS operon are important bacterial factors conferring survival advantage or invasiveness. The high incidence of scarlet fever in children less than 10 years old suggests that the lack of protective immunity is an important host factor. A high population density, overcrowded living environment and a low yearly rainfall are environmental factors contributing to outbreak development. Inappropriate antibiotic use is not only ineffective for treatment, but may actually drive an epidemic caused by drug-resistant strains and worsen patient outcomes by increasing the bacterial density at the site of infection and inducing toxin production. Surveillance of severe S. pyogenes infection is important because it can complicate concurrent chickenpox and influenza. Concomitant outbreaks of these two latter infections with a highly virulent and drug-resistant S. pyogenes strain can be disastrous. PMID:26038416

  4. Streptococcus pyogenes triggers activation of the human contact system by streptokinase.

    PubMed

    Nitzsche, Ramona; Rosenheinrich, Maik; Kreikemeyer, Bernd; Oehmcke-Hecht, Sonja

    2015-08-01

    Severe invasive infectious diseases remain a major and life-threatening health problem. In serious cases, a systemic activation of the coagulation cascade is a critical complication that is associated with high mortality rates. We report here that streptokinase, a group A streptococcal plasminogen activator, triggers the activation of the human contact system. Activation of contact system factors at the surface of the Streptococcus pyogenes serotype M49 is dependent on streptokinase and plasminogen. Our results also show that secreted streptokinase is an efficient contact system activator, independent from a contact surface. This results in the processing of high-molecular-weight kininogen and the release of bradykinin, a potent vascular mediator. We further investigated whether the ability of 50 different clinical S. pyogenes isolates to activate the contact system is associated with an invasive phenotype. The data reveal that isolates from invasive infections trigger an activation of the contact system more potently than strains isolated from noninvasive infections. The present study gives new insights into the mechanisms by which S. pyogenes triggers the human contact system and stresses the function of soluble and surface located plasmin exploited as a group A streptococcal virulence factor through the action of streptokinase. PMID:25987706

  5. The FbaB-type fibronectin-binding protein of Streptococcus pyogenes promotes specific invasion into endothelial cells

    PubMed Central

    Amelung, Silva; Nerlich, Andreas; Rohde, Manfred; Spellerberg, Barbara; Cole, Jason N.; Nizet, Victor; Chhatwal, Gursharan S.; Talay, Susanne R.

    2016-01-01

    Summary Invasive serotype M3 Streptococcus pyogenes are among the most frequently isolated organisms from patients suffering from invasive streptococcal disease and have the potential to invade primary human endothelial cells (EC) via a rapid and efficient mechanism. FbaB protein, the fibronectin-binding protein expressed by M3 S. pyogenes, was herein identified as a potent invasin for EC. By combining heterologous gene expression with allelic replacement, we demonstrate that FbaB is essential and sufficient to trigger EC invasion via a Rac1-dependent phagocytosis-like uptake. FbaB-mediated uptake follows the classical endocytic pathway with lysosomal destination. FbaB is demonstrated to be a streptococcal invasin exhibiting EC tropism. FbaB thus initiates a process that may contribute to the deep tissue tropism and spread of invasive S. pyogenes isolates into the vascular EC lining. PMID:21615663

  6. Biofilm Formation Enhances Fomite Survival of Streptococcus pneumoniae and Streptococcus pyogenes

    PubMed Central

    Marks, Laura R.; Reddinger, Ryan M.

    2014-01-01

    Both Streptococcus pyogenes and Streptococcus pneumoniae are widely thought to rapidly die outside the human host, losing infectivity following desiccation in the environment. However, to date, all literature investigating the infectivity of desiccated streptococci has used broth-grown, planktonic populations. In this study, we examined the impact of biofilm formation on environmental survival of clinical and laboratory isolates of S. pyogenes and S. pneumoniae as both organisms are thought to colonize the human host as biofilms. Results clearly demonstrate that while planktonic cells that are desiccated rapidly lose viability both on hands and abiotic surfaces, such as plastic, biofilm bacteria remain viable over extended periods of time outside the host and remain infectious in a murine colonization model. To explore the level and extent of streptococcal fomite contamination that children might be exposed to naturally, direct bacteriologic cultures of items in a day care center were conducted, which demonstrated high levels of viable streptococci of both species. These findings raise the possibility that streptococci may survive in the environment and be transferred from person to person via fomites contaminated with oropharyngeal secretions containing biofilm streptococci. PMID:24371220

  7. [Multifocal inflammatory syndrome after invasive infection due to an M1 strain of Streptococcus pyogenes].

    PubMed

    Filleron, A; Marchandin, H; Rodière, M; Jeziorski, E

    2010-09-01

    We report on a case of Streptococcus pyogenes invasive disease with toxic shock syndrome due to an M1 strain producing SpeA and SmeZ superantigenic toxins. Post-streptococcal sequelae included several episodes of reactive arthritis and orchitis whose outcome was favorable with corticosteroid therapy. Invasive streptococcal infections are increasingly reported and may associate septic, toxinic, and immunological diseases. High-grade systemic inflammation may induce nonsuppurative complications and autoimmune diseases by molecular mimicry. Among them, reactive arthritis has been recognized as a separate entity from acute rheumatic fever and post-streptococcal orchitis has not been described before. Treatment should be quickly started and should be effective on the etiologic agent but also on its toxins due to the severity of the invasive infections associated with the spread of highly virulent bacterial clones and the potential development of multifocal nonsuppurative sequelae. PMID:20709506

  8. Identification of an Insertion Sequence Located in a Region Encoding Virulence Factors of Streptococcus pyogenes

    PubMed Central

    Berge, Andreas; Rasmussen, Magnus; Björck, Lars

    1998-01-01

    An insertion sequence, IS1562, was identified in a Streptococcus pyogenes strain of the clinically important M1 serotype. IS1562 is located in the mga regulon between the genes coding for the M protein and the C5a peptidase, both important virulence factors. The same or similar insertion sequences were found in most S. pyogenes strains, but the chromosomal location differed among isolates. PMID:9632622

  9. Severe invasive streptococcal infection by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.

    PubMed

    Watanabe, Shinya; Takemoto, Norihiko; Ogura, Kohei; Miyoshi-Akiyama, Tohru

    2016-01-01

    Streptococcus pyogenes, a group A Streptococcus (GAS), has been recognized as the causative pathogen in patients with severe invasive streptococcal infection with or without necrotizing fasciitis. In recent epidemiological studies, Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been isolated from severe invasive streptococcal infection. Complete genome sequence showed that SDSE is the closest bacterial species to GAS, with approximately 70% of genome coverage. SDSE, however, lacks several key virulence factors present in GAS, such as SPE-B, the hyaluronan synthesis operon and active superantigen against human immune cells. A key event in the ability of GAS to cause severe invasive streptococcal infection was shown to be the acquisition of novel genetic traits such as phages. Strikingly, however, during severe invasive infection, GAS destroys its own covRS two-component system, which negatively regulates many virulence factor genes, resulting in a hyper-virulent phenotype. In contrast, this phenomenon has not been observed in SDSE. The present review describes the epidemiology of severe invasive streptococcal infection and the detailed pathogenic mechanisms of GAS and SDSE, emphasizing findings from their genome sequences and analyses of gene expression. PMID:26762200

  10. Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes.

    PubMed

    Hall, Michael; Nylander, Sa; Jenkinson, Howard F; Persson, Karina

    2014-01-01

    The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat) as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins found on the surfaces of most oral streptococci and are involved in host colonization and biofilm formation. In the present study we have determined the crystal structure of the C2-3-domain of the antigen I/II type protein AspA from S. pyogenes M type 28. The structure was solved to 1.8 resolution and shows that the C2-3-domain is comprised of two structurally similar DEv-IgG motifs, designated C2 and C3, both containing a stabilizing covalent isopeptide bond. Furthermore a metal binding site is identified, containing a bound calcium ion. Despite relatively low sequence identity, interestingly, the overall structure shares high similarity to the C2-3-domains of antigen I/II proteins from Streptococcus gordonii and Streptococcus mutans, although certain parts of the structure exhibit distinct features. In summary this work constitutes the first step in the full structure determination of the AspA protein from S. pyogenes. PMID:24918040

  11. Susceptibility and emm type of Streptococcus pyogenes isolated from children with severe infection.

    PubMed

    Sakata, Hiroshi

    2013-12-01

    Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of various antimicrobial agents were measured against 12 strains of Streptococcus pyogenes isolated from children with invasive infections between 2003 and 2012. The patients ranged in age from 1 day to 15 years, with patients younger than 5 years, including three neonates, accounting for a half of the patients. The disease was sepsis in four patients, skin and soft tissue infection in three patients, retropharyngeal abscess in two patients, pneumonia plus sepsis in one patient, empyema in one patient, and pyogenic arthritis in one patient. One patient with sepsis died, while cure without sequelae was achieved in all the remaining patients. When classified by type, emm1 (six strains) was the most prevalent type, followed by emm12 (two strains). The MIC90/MBC90 values were 0.015/0.015 μg/mL for penicillin G, 0.03/0.03 μg/mL for ampicillin, 0.015/0.03 μg/mL for cefotaxime, 0.03/0.03 μg/mL for ceftriaxone, 0.008/0.008 μg/mL for panipenem, 0.008/0.008 μg/mL for meropenem, and ≤0.004/≤0.004 μg/mL for doripenem, indicating the superior antimicrobial activities of carbapenem. PMID:23703641

  12. Recombination between Streptococcus suis ICESsu32457 and Streptococcus agalactiae ICESa2603 yields a hybrid ICE transferable to Streptococcus pyogenes.

    PubMed

    Marini, Emanuela; Palmieri, Claudio; Magi, Gloria; Facinelli, Bruna

    2015-07-01

    Integrative conjugative elements (ICEs) are mobile genetic elements that reside in the chromosome but retain the ability to undergo excision and to transfer by conjugation. Genes involved in drug resistance, virulence, or niche adaptation are often found among backbone genes as cargo DNA. We recently characterized in Streptococcus suis an ICE (ICESsu32457) carrying resistance genes [tet(O/W/32/O), tet(40), erm(B), aphA, and aadE] in the 15K unstable genetic element, which is flanked by two ?1.3kb direct repeats. Remarkably, ?1.3-kb sequences are conserved in ICESa2603 of Streptococcus agalactiae 2603V/R, which carry heavy metal resistance genes cadC/cadA and mer. In matings between S. suis 32457 (donor) and S. agalactiae 2603V/R (recipient), transconjugants were obtained. PCR experiments, PFGE, and sequence analysis of transconjugants demonstrated a tandem array between ICESsu32457 and ICESa2603. Matings between tandem array-containing S. agalactiae 2603V/R (donor) and Streptococcus pyogenes RF12 (recipient) yielded a single transconjugant containing a hybrid ICE, here named ICESa2603/ICESsu32457. The hybrid formed by recombination of the left ?1.3-kb sequence of ICESsu32457 and the ?1.3-kb sequence of ICESa2603. Interestingly, the hybrid ICE was transferable between S. pyogenes strains, thus demonstrating that it behaves as a conventional ICE. These findings suggest that both tandem arrays and hybrid ICEs may contribute to the evolution of antibiotic resistance in streptococci, creating novel mobile elements capable of disseminating new combinations of antibiotic resistance genes. PMID:25935120

  13. HMGB1 in severe soft tissue infections caused by Streptococcus pyogenes.

    PubMed

    Johansson, Linda; Snäll, Johanna; Sendi, Parham; Linnér, Anna; Thulin, Pontus; Linder, Adam; Treutiger, Carl-Johan; Norrby-Teglund, Anna

    2014-01-01

    Extracellular High Mobility Group Box 1 (HMGB1) has been associated with acute and chronic inflammatory conditions. However, little is known about HMGB1 in necrotizing bacterial infections. We hypothesized that the local HMGB1 response is excessive in severe soft tissue infections (STIs), which are characterized by necrosis and hyperinflammation. To explore this, tissue biopsies were collected from patients with varying severity of Streptococcus pyogenes skin and STIs, including erysipelas, cellulitis, and necrotizing fasciitis. Tissue sections were immunostained for HMGB1, S. pyogenes, and inflammatory cell infiltrates and results quantified by acquired computerized image analysis (ACIA). HMGB1 expression increased in parallel to disease severity and was significantly higher in necrotizing fasciitis than in erysipelas (p = 0.0023). Confocal microscopy of sections co-stained for HMGB1 and cell markers revealed both extracellular and cytoplasmic HMGB1, the latter of which was found predominantly in macrophages. To further verify macrophages as main source of activation triggered HMGB1 release, human macrophages were infected with clinical S. pyogenes isolates. The results demonstrated infection triggered release of HMGB1. Dual staining's visualized HMGB1 in areas close to, but not overlapping, with neutrophils, indicating a potential chemotactic role. In vitro transmigration experiments showed a chemotactic effect of HMGB1 on neutrophils. The data furthermore provided in vivo support that HGMB1 may form immunostimulatory complexes with IL-1β. Taken together, the findings provide the first in vivo evidence that HMGB1 is abundant at the local site of severe bacterial STIs and its levels correlated to severity of infections; hence, indicating its potential value as a biomarker for tissue pathology. PMID:24524027

  14. Characterization of Streptococcus pyogenes isolates responsible for adult meningitis in France from 2003 to 2013.

    PubMed

    Plainvert, Céline; Doloy, Alexandra; Joubrel, Caroline; Maataoui, Naouale; Dmytruk, Nicolas; Touak, Gérald; Collobert, Gislène; Fouet, Agnès; Poyart, Claire; Loubinoux, Julien

    2016-04-01

    Sixty-three cases of Streptococcus pyogenes meningitis in adults were studied. Three predominant emm types were associated with meningitis: emm1 (44%), emm3 (11%), and emm6 (11%). Streptococcal toxic shock syndrome and mortality rates were 40% and 38%, respectively. PMID:26846900

  15. Complete Genome Sequences of emm6 Streptococcus pyogenes JRS4 and Parental Strain D471

    PubMed Central

    Port, Gary C.; Paluscio, Elyse

    2015-01-01

    We report the complete genome assemblies of the group A Streptococcus pyogenes serotype emm6 strain D471 and its streptomycin-resistant derivative JRS4. Both of these well-studied laboratory strains have been extensively characterized over the past three decades and have been instrumental in the discovery of multiple aspects of streptococcal pathogenesis. PMID:26139722

  16. Identification of the Streptococcus pyogenes surface antigens recognised by pooled human immunoglobulin

    PubMed Central

    Reglinski, Mark; Gierula, Magdalena; Lynskey, Nicola N.; Edwards, Robert J.; Sriskandan, Shiranee

    2015-01-01

    Immunity to common bacteria requires the generation of antibodies that promote opsonophagocytosis and neutralise toxins. Pooled human immunoglobulin is widely advocated as an adjunctive treatment for clinical Streptococcus pyogenes infection however, the protein targets of the reagent remain ill defined. Affinity purification of the anti-streptococcal antibodies present within pooled immunoglobulin resulted in the generation of an IgG preparation that promoted opsonophagocytic killing of S. pyogenes in vitro and provided passive immunity in vivo. Isolation of the streptococcal surface proteins recognised by pooled human immunoglobulin permitted identification and ranking of 94 protein antigens, ten of which were reproducibly identified across four contemporary invasive S. pyogenes serotypes (M1, M3, M12 and M89). The data provide novel insight into the action of pooled human immunoglobulin during invasive S. pyogenes infection, and demonstrate a potential route to enhance the efficacy of antibody based therapies. PMID:26508447

  17. Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes

    PubMed Central

    HAMADA, Shigeyuki; KAWABATA, Shigetada; NAKAGAWA, Ichiro

    2015-01-01

    Group A streptococcus (GAS) or Streptococcus pyogenes causes various diseases ranging from self-limiting sore throat to deadly invasive diseases. The genome size of GAS is 1.85–1.9 Mb, and genomic rearrangement has been demonstrated. GAS possesses various surface-associated substances such as hyaluronic capsule, M proteins, and fibronectin/laminin/immunoglobulin-binding proteins. These are related to the virulence and play multifaceted and mutually reflected roles in the pathogenesis of GAS infections. Invasion of GAS into epithelial cells and deeper tissues provokes immune and non-immune defense or inflammatory responses including the recruitment of neutrophils, macrophages, and dendritic cells in hosts. GAS frequently evades host defense mechanisms by using its virulence factors. Extracellular products of GAS may perturb cellular and subcellular functions and degrade tissues enzymatically, which leads to the aggravation of local and/or systemic disorders in the host. In this review, we summarize some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these. PMID:26666305

  18. Chromosomal islands of Streptococcus pyogenes and related streptococci: molecular switches for survival and virulence.

    PubMed

    Nguyen, Scott V; McShan, William M

    2014-01-01

    Streptococcus pyogenes is a significant pathogen of humans, annually causing over 700,000,000 infections and 500,000 deaths. Virulence in S. pyogenes is closely linked to mobile genetic elements like phages and chromosomal islands (CI). S. pyogenes phage-like chromosomal islands (SpyCI) confer a complex mutator phenotype on their host. SpyCI integrate into the 5' end of DNA mismatch repair (MMR) gene mutL, which also disrupts downstream operon genes lmrP, ruvA, and tag. During early logarithmic growth, SpyCI excise from the bacterial chromosome and replicate as episomes, relieving the mutator phenotype. As growth slows and the cells enter stationary phase, SpyCI reintegrate into the chromosome, again silencing the MMR operon. This system creates a unique growth-dependent and reversible mutator phenotype. Additional CI using the identical attachment site in mutL have been identified in related species, including Streptococcus dysgalactiae subsp. equisimilis, Streptococcus anginosus, Streptococcus intermedius, Streptococcus parauberis, and Streptococcus canis. These CI have small genomes, which range from 13 to 20 kB, conserved integrase and DNA replication genes, and no identifiable genes encoding capsid proteins. SpyCI may employ a helper phage for packaging and dissemination in a fashion similar to the Staphylococcus aureus pathogenicity islands (SaPI). Outside of the core replication and integration genes, SpyCI and related CI show considerable diversity with the presence of many indels that may contribute to the host cell phenotype or fitness. SpyCI are a subset of a larger family of streptococcal CI who potentially regulate the expression of other host genes. The biological and phylogenetic analysis of streptococcal chromosomal islands provides important clues as to how these chromosomal islands help S. pyogenes and other streptococcal species persist in human populations in spite of antibiotic therapy and immune challenges. PMID:25161960

  19. Chromosomal islands of Streptococcus pyogenes and related streptococci: molecular switches for survival and virulence

    PubMed Central

    Nguyen, Scott V.; McShan, William M.

    2014-01-01

    Streptococcus pyogenes is a significant pathogen of humans, annually causing over 700,000,000 infections and 500,000 deaths. Virulence in S. pyogenes is closely linked to mobile genetic elements like phages and chromosomal islands (CI). S. pyogenes phage-like chromosomal islands (SpyCI) confer a complex mutator phenotype on their host. SpyCI integrate into the 5? end of DNA mismatch repair (MMR) gene mutL, which also disrupts downstream operon genes lmrP, ruvA, and tag. During early logarithmic growth, SpyCI excise from the bacterial chromosome and replicate as episomes, relieving the mutator phenotype. As growth slows and the cells enter stationary phase, SpyCI reintegrate into the chromosome, again silencing the MMR operon. This system creates a unique growth-dependent and reversible mutator phenotype. Additional CI using the identical attachment site in mutL have been identified in related species, including Streptococcus dysgalactiae subsp. equisimilis, Streptococcus anginosus, Streptococcus intermedius, Streptococcus parauberis, and Streptococcus canis. These CI have small genomes, which range from 13 to 20 kB, conserved integrase and DNA replication genes, and no identifiable genes encoding capsid proteins. SpyCI may employ a helper phage for packaging and dissemination in a fashion similar to the Staphylococcus aureus pathogenicity islands (SaPI). Outside of the core replication and integration genes, SpyCI and related CI show considerable diversity with the presence of many indels that may contribute to the host cell phenotype or fitness. SpyCI are a subset of a larger family of streptococcal CI who potentially regulate the expression of other host genes. The biological and phylogenetic analysis of streptococcal chromosomal islands provides important clues as to how these chromosomal islands help S. pyogenes and other streptococcal species persist in human populations in spite of antibiotic therapy and immune challenges. PMID:25161960

  20. Streptococcus pyogenes degrades extracellular matrix in chondrocytes via MMP-13

    SciTech Connect

    Sakurai, Atsuo; Okahashi, Nobuo; Maruyama, Fumito; Ooshima, Takashi; Hamada, Shigeyuki; Nakagawa, Ichiro

    2008-08-29

    Group A streptococcus (GAS) causes a wide range of human diseases, including bacterial arthritis. The pathogenesis of arthritis is characterized by synovial proliferation and the destruction of cartilage and subchondral bone in joints. We report here that GAS strain JRS4 invaded a chondrogenic cell line ATDC5 and induced the degradation of the extracellular matrix (ECM), whereas an isogenic mutant of JRS4 lacking a fibronectin-binding protein, SAM1, failed to invade the chondrocytes or degrade the ECM. Reverse transcription-PCR and Western blot analysis revealed that the expression of matrix metalloproteinase (MMP)-13 was strongly elevated during the infection with GAS. A reporter assay revealed that the activation of the AP-1 transcription factor and the phosphorylation of c-Jun terminal kinase participated in MMP-13 expression. These results suggest that MMP-13 plays an important role in the destruction of infected joints during the development of septic arthritis.

  1. Six-Month Multicenter Study on Invasive Infections Due to Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis in Argentina

    PubMed Central

    Lopardo, Horacio A.; Vidal, Patricia; Sparo, Monica; Jeric, Paola; Centron, Daniela; Facklam, Richard R.; Paganini, Hugo; Pagniez, N. Gaston; Lovgren, Marguerite; Beall, Bernard

    2005-01-01

    During a 6-month period, 95 invasive infections due to Streptococcus pyogenes and group C or group G Streptococcus dysgalactiae subsp. equisimilis were recorded from 40 centers of 16 cities in Argentina. We describe here epidemiologic data available for 55 and 19 patients, respectively, associated with invasive infections due to S. pyogenes and S. dysgalactiae subsp. equisimilis. The associated isolates and 58 additional pharyngeal isolates were genotyped and subjected to serologic and/or antibiotic susceptibility testing. Group A streptococcal emm type distribution and strain association with toxic shock appeared to differ somewhat from results found within the United States; however, serologic characterization and sof sequence typing suggested that emm types found in both countries are reflective of shared clonal types. PMID:15695683

  2. Purification, crystallization and preliminary crystallographic analysis of Streptococcus pyogenes laminin-binding protein Lbp

    SciTech Connect

    Linke, Christian; Caradoc-Davies, Tom T.; Proft, Thomas; Baker, Edward N.

    2008-02-01

    The S. pyogenes laminin-binding protein Lbp, which is essential for adhesion to human laminin, has been expressed, purified and crystallized. The laminin-binding protein Lbp (Spy2007) from Streptococcus pyogenes (a group A streptococcus) mediates adhesion to the human basal lamina glycoprotein laminin. Accordingly, Lbp is essential in in vitro models of cell adhesion and invasion. However, the molecular and structural basis of laminin binding by bacteria remains unknown. Therefore, the lbp gene has been cloned for recombinant expression in Escherichia coli. Lbp has been purified and crystallized from 30%(w/v) PEG 1500 by the sitting-drop vapour-diffusion method. The crystals belonged to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 42.62, b = 92.16, c = 70.61 Å, β = 106.27°, and diffracted to 2.5 Å resolution.

  3. Serine/Threonine Protein Kinase Stk Is Required for Virulence, Stress Response, and Penicillin Tolerance in Streptococcus pyogenes?

    PubMed Central

    Bugrysheva, Julia; Froehlich, Barbara J.; Freiberg, Jeffrey A.; Scott, June R.

    2011-01-01

    Genes encoding one or more Ser/Thr protein kinases have been identified recently in many bacteria, including one (stk) in the human pathogen Streptococcus pyogenes (group A streptococcus [GAS]). We report that in GAS, stk is required to produce disease in a murine myositis model of infection. Using microarray and quantitative reverse transcription-PCR (qRT-PCR) studies, we found that Stk activates genes for virulence factors, osmoregulation, metabolism of ?-glucans, and fatty acid biosynthesis, as well as genes affecting cell wall synthesis. Confirming these transcription studies, we determined that the stk deletion mutant is more sensitive to osmotic stress and to penicillin than the wild type. We discuss several possible Stk phosphorylation targets that might explain Stk regulation of expression of specific operons and the possible role of Stk in resuscitation from quiescence. PMID:21788381

  4. Complete Genome Assembly of Streptococcus pyogenes ATCC 19615, a Group A ?-Hemolytic Reference Strain.

    PubMed

    Minogue, T D; Daligault, H A; Davenport, K W; Bishop-Lilly, K A; Broomall, S M; Bruce, D C; Chain, P S; Chertkov, O; Coyne, S R; Freitas, T; Frey, K G; Gibbons, H S; Jaissle, J; Redden, C L; Rosenzweig, C N; Xu, Y; Johnson, S L

    2014-01-01

    We present the complete genome assembly of Streptococcus pyogenes ATCC 19615 (Rosenbach) as submitted to GenBank under accession number CP008926. This group A nonmotile ?-hemolytic clinical isolate is used for quality control in a variety of commercially available tests. The assembled genome is 1.84Mb (38.5% G+C content) and contains 1,788 coding regions. PMID:25258274

  5. Streptolysin S Inhibits Neutrophil Recruitment during the Early Stages of Streptococcus pyogenes Infection?

    PubMed Central

    Lin, Ada; Loughman, Jennifer A.; Zinselmeyer, Bernd H.; Miller, Mark J.; Caparon, Michael G.

    2009-01-01

    In contrast to infection of superficial tissues, Streptococcus pyogenes infection of deeper tissue can be associated with a significantly diminished inflammatory response, suggesting that this bacterium has the ability to both promote and suppress inflammation. To examine this, we analyzed the behavior of an S. pyogenes mutant deficient in expression of the cytolytic toxin streptolysin S (SLS?) and evaluated events that occur during the first few hours of infection by using several models including injection of zebrafish (adults, larvae, and embryos), a transepithelial polymorphonuclear leukocyte (PMN) migration assay, and two-photon microscopy of mice in vivo. In contrast to wild-type S. pyogenes, the SLS? mutant was associated with the robust recruitment of neutrophils and significantly reduced lethal myositis in adult zebrafish. Similarly, the mutant was attenuated in embryos in its ability to cause lethality. Infection of larva muscle allowed an analysis of inflammation in real time, which revealed that the mutant had recruited PMNs to the infection site. Analysis of transepithelial migration in vitro suggested that SLS inhibited the host cells' production of signals chemotactic for neutrophils, which contrasted with the proinflammatory effect of an unrelated cytolytic toxin, streptolysin O. Using two-photon microscopy of mice in vivo, we showed that the extravasation of neutrophils during infection with SLS? mutant bacteria was significantly accelerated compared to infection with wild-type S. pyogenes. Taken together, these data support a role for SLS in the inhibition of neutrophil recruitment during the early stages of S. pyogenes infection. PMID:19687200

  6. Kinetics of cytokine profile in response to Mycobacterium bovis BCG and Streptococcus pyogenes activated cells.

    PubMed

    Verma, Vivek; Kumar, Parveen; Dhanda, Rakesh Singh; Yadav, Manisha

    2016-06-01

    The infection of epithelial cells is a necessary step for Mycobacterium bovis BCG dissemination, but the mechanism of mycobacterial epithelial interactions is not completely understood. Similarly, Streptococcus pyogenes is a strictly human pathogen that favorably colonizes the skin and the pharynx. Effective cytokine secretion is essential in order to fabricate a suitable inflammatory response against an infection. In this data article, the cytokine profile in BCG and S. pyogenes activated THP-1 cell line in media after the acute phase of infection by ELISA is described. The interleukin-8 level was increased in response to both BCG and S. pyogenes, but was quite prominent after 24 h and further increased upto 72 h post infection. On the other hand, an increase in IL-6 response to S. pyogenes was observed while there was no response to BCG even after 48 h of infection. A low level of TNF-α was detected upon BCG and S. pyogenes infection. PMID:27014727

  7. Kinetics of cytokine profile in response to Mycobacterium bovis BCG and Streptococcus pyogenes activated cells

    PubMed Central

    Verma, Vivek; Kumar, Parveen; Dhanda, Rakesh Singh; Yadav, Manisha

    2016-01-01

    The infection of epithelial cells is a necessary step for Mycobacterium bovis BCG dissemination, but the mechanism of mycobacterial epithelial interactions is not completely understood. Similarly, Streptococcus pyogenes is a strictly human pathogen that favorably colonizes the skin and the pharynx. Effective cytokine secretion is essential in order to fabricate a suitable inflammatory response against an infection. In this data article, the cytokine profile in BCG and S. pyogenes activated THP-1 cell line in media after the acute phase of infection by ELISA is described. The interleukin-8 level was increased in response to both BCG and S. pyogenes, but was quite prominent after 24 h and further increased upto 72 h post infection. On the other hand, an increase in IL-6 response to S. pyogenes was observed while there was no response to BCG even after 48 h of infection. A low level of TNF-α was detected upon BCG and S. pyogenes infection.

  8. Inactivation of the Rgg2 Transcriptional Regulator Ablates the Virulence of Streptococcus pyogenes

    PubMed Central

    Zutkis, Anastasia A.; Anbalagan, Srivishnupriya; Chaussee, Michael S.; Dmitriev, Alexander V.

    2014-01-01

    Streptococcus pyogenes adapts to different niches encountered in the human host via the activity of numerous regulatory proteins including the Rgg family of transcriptional regulators. The S. pyogenes chromosome encodes four Rgg paralogues designated Rgg1 (RopB), Rgg2 (MutR), Rgg3, and Rgg4 (ComR). In order to understand the role of the Rgg2 protein in the regulation of metabolic and virulence-associated properties of S. pyogenes, the rgg2 gene was inactivated in the M1 serotype strain SF370. Inactivation of rgg2 increased the growth yield of S. pyogenes in THY broth, increased biofilm formation, and increased production of SIC, which is an important virulence factor that inhibits complement mediated lysis. To identify Rgg2-regulated genes, the transcriptomes of SF370 and the rgg2 mutant strains were compared in the middle-exponential and post-exponential phases of growth. Rgg2 was found to control the expression of dozens of genes primarily in the exponential phase of growth, including genes associated with virulence (sse, scpA, slo, nga, mf-3), DNA transformation, and nucleotide metabolism. Inactivation of rgg2 decreased the ability of S. pyogenes to adhere to epithelial cells. In addition, the mutant strain was more sensitive to killing when incubated with human blood and avirulent in a murine bacteremia model. Finally, inoculation of mice with the avirulent rgg2 mutant of S. pyogenes SF370 conferred complete protection to mice subsequently challenged with the wild-type strain. Restoration of an intact rgg2 gene in mutant strain restored the wild-type phenotypes. Overall, the results demonstrate that Rgg2 is an important regulatory protein in S. pyogenes involved in controlling genes associated with both metabolism and virulence. PMID:25486272

  9. Novel impedimetric immunosensor for detection of pathogenic bacteria Streptococcus pyogenes in human saliva.

    PubMed

    Ahmed, Asif; Rushworth, Jo V; Wright, John D; Millner, Paul A

    2013-12-17

    Streptococcus pyogenes , also known as group A streptococcus (GAS), is a Gram positive human pathogen responsible for invasive and noninvasive human infections with a high incidence rate. Traditional detection methods involve cell culture and PCR, which are limited by long processing times or the need for high cost equipment. Impedance-based electrochemical immunosensors provide an alternative by which precise and rapid quantitative detection of the organism can help with rapid clinical decisions. To bring a biosensor for point-of-care applications to market, strict optimization of each level of construction and operation is required. In this paper, commercial screen-printed gold electrodes have been used to construct polytyramine (Ptyr)-based immunosensors. Biotin tagged whole antibodies against S. pyogenes were conjugated to Ptyr amine group via biotin-NeutrAvidin coupling. Sensors were optimized at each level of construction, particularly for Ptyr electrodeposition and antibody concentration, to optimize signal and specificity. Scanning electron microscopy, fluorescence microscopy, and on-sensor analysis (HRP conjugated enhanced chemiluminescence-based semiquantitative method) to detect Ptyr surface amine and bound antibody were performed as supporting techniques. Cumulative and single shot incubations had shown detection range of 100 to 10(5) cells per 10 ?L and 100 to 10(4) cells per 10 ?L of bacteria in PBS, respectively. Sensors were also able to specifically detect S. pyogenes in 50% (v/v) human saliva, with good selectivity and low cross-reactivity. PMID:24256123

  10. Transduction of the Streptococcus pyogenes bacteriophage ?m46.1, carrying resistance genes mef(A) and tet(O), to other Streptococcus species.

    PubMed

    Giovanetti, Eleonora; Brenciani, Andrea; Morroni, Gianluca; Tiberi, Erika; Pasquaroli, Sonia; Mingoia, Marina; Varaldo, Pietro E

    2014-01-01

    ?m46.1 - Streptococcus pyogenes bacteriophage carrying mef(A) and tet(O), respectively, encoding resistance to macrolides (M phenotype) and tetracycline - is widespread in S. pyogenes but has not been reported outside this species. ?m46.1 is transferable in vitro among S. pyogenes isolates, but no information is available about its transferability to other Streptococcus species. We thus investigated ?m46.1 for its ability to be transduced in vitro to recipients of different Streptococcus species. Transductants were obtained from recipients of Streptococcus agalactiae, Streptococcus gordonii, and Streptococcus suis. Retransfer was always achieved, and from S. suis to S. pyogenes occurred at a much greater frequency than in the opposite direction. In transductants ?m46.1 retained its functional properties, such as inducibility with mitomycin C, presence both as a prophage and as a free circular form, and transferability. The transductants shared the same ?m46.1 chromosomal integration site as the donor, at the 3' end of a conserved RNA uracil methyltransferase (rum) gene, which is an integration hotspot for a variety of genetic elements. No transfer occurred to recipients of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus salivarius, even though rum-like genes were also detected in the sequenced genomes of these species. A largely overlapping 18-bp critical sequence, where the site-specific recombination process presumably takes place, was identified in the rum genes of all recipients, including those of the species yielding no transductants. Growth assays to evaluate the fitness cost of ?m46.1 acquisition disclosed a negligible impact on S. pyogenes, S. agalactiae, and S. gordonii transductants and a noticeable fitness advantage in S. suis. The S. suis transductant also displayed marked overexpression of the autolysin-encoding gene atl. PMID:25620959

  11. Antibacterial Activity of Rhodomyrtus tomentosa (Aiton) Hassk. Leaf Extract against Clinical Isolates of Streptococcus pyogenes

    PubMed Central

    Limsuwan, Surasak; Kayser, Oliver; Voravuthikunchai, Supayang Piyawan

    2012-01-01

    Ethanol extract of Rhodomyrtus tomentosa (Aiton) Hassk. leaf was evaluated for antibacterial activity against 47 clinical isolates of Streptococcus pyogenes. The extract exhibited good anti-S. pyogenes activity against all the tested isolates with similar minimum inhibitory concentration (MIC, 3.9162.5??g?mL?1) and minimum bactericidal concentration (MBC, 3.9162.5??g?mL?1) ranges. No surviving cells were detected at 16 h after treatment with 8??MIC of the extract. The extract-treated cells demonstrated no lysis and cytoplasmic leakage through the bacterial membrane. Electron micrographs further revealed that the extract did not cause any dramatic changes on the treated cells. Rhodomyrtone, an isolated compound, exhibited good anti-S. pyogenes activity (14 isolates), expressed very low MIC (0.391.56??g?mL?1) and MBC (0.39-1.56??g?mL?1) values. Rhodomyrtus tomentosa leaf extract and rhodomyrtone displayed promising antibacterial activity against clinical isolates of S. pyogenes. PMID:22973404

  12. Antibacterial Activity of Rhodomyrtus tomentosa (Aiton) Hassk. Leaf Extract against Clinical Isolates of Streptococcus pyogenes.

    PubMed

    Limsuwan, Surasak; Kayser, Oliver; Voravuthikunchai, Supayang Piyawan

    2012-01-01

    Ethanol extract of Rhodomyrtus tomentosa (Aiton) Hassk. leaf was evaluated for antibacterial activity against 47 clinical isolates of Streptococcus pyogenes. The extract exhibited good anti-S. pyogenes activity against all the tested isolates with similar minimum inhibitory concentration (MIC, 3.91-62.5??g?mL(-1)) and minimum bactericidal concentration (MBC, 3.91-62.5??g?mL(-1)) ranges. No surviving cells were detected at 16 h after treatment with 8??MIC of the extract. The extract-treated cells demonstrated no lysis and cytoplasmic leakage through the bacterial membrane. Electron micrographs further revealed that the extract did not cause any dramatic changes on the treated cells. Rhodomyrtone, an isolated compound, exhibited good anti-S. pyogenes activity (14 isolates), expressed very low MIC (0.39-1.56??g?mL(-1)) and MBC (0.39-1.56??g?mL(-1)) values. Rhodomyrtus tomentosa leaf extract and rhodomyrtone displayed promising antibacterial activity against clinical isolates of S. pyogenes. PMID:22973404

  13. Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes

    PubMed Central

    Patenge, Nadja; Pappesch, Roberto; Krawack, Franziska; Walda, Claudia; Mraheil, Mobarak Abu; Jacob, Anette; Hain, Torsten; Kreikemeyer, Bernd

    2013-01-01

    While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e.g., macrolides, has increased. Taken together, these facts demand the development of novel therapeutic strategies. In this study, S. pyogenes growth was inhibited by application of peptide-conjugated antisense-peptide nucleic acids (PNAs) specific for the essential gyrase A gene (gyrA). Thereby, HIV-1 Tat peptide-coupled PNAs were more efficient inhibitors of streptococcal growth as compared with (KFF)3K-coupled PNAs. Peptide-anti-gyrA PNAs decreased the abundance of gyrA transcripts in S. pyogenes. Growth inhibition by antisense interference was enhanced by combination of peptide-coupled PNAs with protein-level inhibitors. Antimicrobial synergy could be detected with levofloxacin and novobiocin, targeting the gyrase enzyme, and with spectinomycin, impeding ribosomal function. The prospective application of carrier peptide-coupled antisense PNAs in S. pyogenes covers the use as an antimicrobial agent and the employment as a knock-down strategy for the investigation of virulence factor function. PMID:24193033

  14. Synergy and Mode of Action of Ceftazidime plus Quercetin or Luteolin on Streptococcus pyogenes

    PubMed Central

    Siriwong, Supatcharee; Thumanu, Kanjana; Hengpratom, Tanaporn; Eumkeb, Griangsak

    2015-01-01

    Streptococcus pyogenes causes streptococcal toxic shock syndrome. The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB). The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against S. pyogenes. The MICs of ceftazidime, luteolin, and quercetin against all S. pyogenes were 0.50, 128, and 128 µg mL−1, respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against β-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1) inhibiting of peptidoglycan synthesis, (2) increasing CM permeability, and (3) decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections. PMID:26576195

  15. Innate Immune Response to Streptococcus pyogenes Depends on the Combined Activation of TLR13 and TLR2

    PubMed Central

    Fieber, Christina; Janos, Marton; Koestler, Tina; Gratz, Nina; Li, Xiao-Dong; Castiglia, Virginia; Aberle, Marion; Sauert, Martina; Wegner, Mareike; Alexopoulou, Lena; Kirschning, Carsten J.; Chen, Zhijian J.; von Haeseler, Arndt; Kovarik, Pavel

    2015-01-01

    Innate immune recognition of the major human-specific Gram-positive pathogen Streptococcus pyogenes is not understood. Here we show that mice employ Toll-like receptor (TLR) 2- and TLR13-mediated recognition of S. pyogenes. These TLR pathways are non-redundant in the in vivo context of animal infection, but are largely redundant in vitro, as only inactivation of both of them abolishes inflammatory cytokine production by macrophages and dendritic cells infected with S. pyogenes. Mechanistically, S. pyogenes is initially recognized in a phagocytosis-independent manner by TLR2 and subsequently by TLR13 upon internalization. We show that the TLR13 response is specifically triggered by S. pyogenes rRNA and that Tlr13−/− cells respond to S. pyogenes infection solely by engagement of TLR2. TLR13 is absent from humans and, remarkably, we find no equivalent route for S. pyogenes RNA recognition in human macrophages. Phylogenetic analysis reveals that TLR13 occurs in all kingdoms but only in few mammals, including mice and rats, which are naturally resistant against S. pyogenes. Our study establishes that the dissimilar expression of TLR13 in mice and humans has functional consequences for recognition of S. pyogenes in these organisms. PMID:25756897

  16. Innate immune response to Streptococcus pyogenes depends on the combined activation of TLR13 and TLR2.

    PubMed

    Fieber, Christina; Janos, Marton; Koestler, Tina; Gratz, Nina; Li, Xiao-Dong; Castiglia, Virginia; Aberle, Marion; Sauert, Martina; Wegner, Mareike; Alexopoulou, Lena; Kirschning, Carsten J; Chen, Zhijian J; von Haeseler, Arndt; Kovarik, Pavel

    2015-01-01

    Innate immune recognition of the major human-specific Gram-positive pathogen Streptococcus pyogenes is not understood. Here we show that mice employ Toll-like receptor (TLR) 2- and TLR13-mediated recognition of S. pyogenes. These TLR pathways are non-redundant in the in vivo context of animal infection, but are largely redundant in vitro, as only inactivation of both of them abolishes inflammatory cytokine production by macrophages and dendritic cells infected with S. pyogenes. Mechanistically, S. pyogenes is initially recognized in a phagocytosis-independent manner by TLR2 and subsequently by TLR13 upon internalization. We show that the TLR13 response is specifically triggered by S. pyogenes rRNA and that Tlr13-/- cells respond to S. pyogenes infection solely by engagement of TLR2. TLR13 is absent from humans and, remarkably, we find no equivalent route for S. pyogenes RNA recognition in human macrophages. Phylogenetic analysis reveals that TLR13 occurs in all kingdoms but only in few mammals, including mice and rats, which are naturally resistant against S. pyogenes. Our study establishes that the dissimilar expression of TLR13 in mice and humans has functional consequences for recognition of S. pyogenes in these organisms. PMID:25756897

  17. Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates, from Which Bacteria Subsequently Escape

    PubMed Central

    Svensson, Lisbeth; Baumgarten, Maria; Mrgelin, Matthias

    2014-01-01

    Platelet activation and aggregation have been reported to occur in response to a number of Gram-positive pathogens. Here, we show that platelet aggregates induced by Streptococcus pyogenes were unstable and that viable bacteria escaped from the aggregates over time. This was not due to differential activation in response to the bacteria compared with physiological activators. All the bacterial isolates induced significant platelet activation, including integrin activation and alpha and dense-granule release, at levels equivalent to those induced by potent physiological platelet activators that induced stable aggregates. The ability to escape the aggregates and to resist the antibacterial effects of platelets was dependent on active protein synthesis by the bacteria within the aggregate. We conclude that S. pyogenes bacteria can temporarily cover themselves with activated platelets, and we propose that this may facilitate survival of the bacteria in the presence of platelets. PMID:25069984

  18. Purification, crystallization and preliminary crystallographic analysis of the minor pilin FctB from Streptococcus pyogenes

    PubMed Central

    Linke, Christian; Young, Paul G.; Kang, Hae Joo; Proft, Thomas; Baker, Edward N.

    2010-01-01

    The minor pilin FctB is an integral part of the pilus assembly expressed by Streptococcus pyogenes. Since it is located at the cell wall, it can be hypothesized that it functions as a cell-wall anchor for the streptococcal pilus. In order to elucidate its structure, the genes for FctB from the S. pyogenes strains 90/306S and SF370 were cloned for overexpression in Escherichia coli. FctB from strain 90/306S was crystallized by the sitting-drop vapour-diffusion method using sodium citrate as a precipitant. The hexagonal FctB crystals belonged to space group P61 or P65, with unit-cell parameters a = b = 95.15, c = 100.25?, and diffracted to 2.9? resolution. PMID:20124716

  19. The Cryptic Competence Pathway in Streptococcus pyogenes Is Controlled by a Peptide Pheromone

    PubMed Central

    Mashburn-Warren, Lauren; Morrison, Donald A.

    2012-01-01

    Horizontal gene transfer is an important means of bacterial evolution that is facilitated by transduction, conjugation, and natural genetic transformation. Transformation occurs after bacterial cells enter a state of competence, where naked DNA is acquired from the extracellular environment. Induction of the competent state relies on signals that activate master regulators, causing the expression of genes involved in DNA uptake, processing, and recombination. All streptococcal species contain the master regulator SigX and SigX-dependent effector genes required for natural genetic transformation; however, not all streptococcal species have been shown to be naturally competent. We recently demonstrated that competence development in Streptococcus mutans requires the type II ComRS quorum-sensing circuit, comprising an Rgg transcriptional activator and a novel peptide pheromone (L. Mashburn-Warren, D. A. Morrison, and M. J. Federle, Mol. Microbiol. 78:589–606, 2010). The type II ComRS system is shared by the pyogenic, mutans, and bovis streptococci, including the clinically relevant pathogen Streptococcus pyogenes. Here, we describe the activation of sigX by a small-peptide pheromone and an Rgg regulator of the type II ComRS class. We confirm previous reports that SigX is functional and able to activate sigX-dependent gene expression within the competence regulon, and that SigX stability is influenced by the cytoplasmic protease ClpP. Genomic analyses of available S. pyogenes genomes revealed the presence of intact genes within the competence regulon. While this is the first report to show natural induction of sigX, S. pyogenes remained nontransformable under laboratory conditions. Using radiolabeled DNA, we demonstrate that transformation is blocked at the stage of DNA uptake. PMID:22730123

  20. The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from streptococcus pyogenes.

    SciTech Connect

    Chang, C.; Coggill, P.; Bateman, A.; Finn, R.; Cymborowski, M.; Otwinowski, Z.; Minor, W.; Volkart, L.; Joachimiak, A.; Wellcome Trust Sanger Inst.; Univ. of Virginia; UT Southwestern Medical Center

    2009-12-17

    Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. We have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.

  1. Intracellular Streptococcus pyogenes in Human Macrophages Display an Altered Gene Expression Profile

    PubMed Central

    Hertzén, Erika; Johansson, Linda; Kansal, Rita; Hecht, Alexander; Dahesh, Samira; Janos, Marton; Nizet, Victor; Kotb, Malak; Norrby-Teglund, Anna

    2012-01-01

    Streptococcus pyogenes is an important human pathogen, which has recently gained recognition as an intracellular microorganism during the course of severe invasive infections such as necrotizing fasciitis. Although the surface anchored M protein has been identified as a pivotal factor affecting phagosomal maturation and S. pyogenes survival within macrophages, the overall transcriptional profile required for the pathogen to adapt and persist intracellularly is as of yet unknown. To address this, the gene expression profile of S. pyogenes within human macrophages was determined and compared to that of extracellular bacteria using customized microarrays and real-time qRT-PCR. In order to model the early phase of infection involving adaptation to the intracellular compartment, samples were collected 2h post-infection. Microarray analysis revealed that the expression of 145 streptococcal genes was significantly altered in the intracellular environment. The majority of differentially regulated genes were associated with metabolic and energy-dependent processes. Key up-regulated genes in early phase intracellular bacteria were ihk and irr, encoding a two-component gene regulatory system (TCS). Comparison of gene expression of selected genes at 2h and 6h post-infection revealed a dramatic shift in response regulators over time with a down-regulation of ihk/irr genes concurring with an up-regulation of the covR/S TCS. In re-infection assays, intracellular bacteria from the 6h time point exhibited significantly greater survival within macrophages than did bacteria collected at the 2h time point. An isogenic S. pyogenes mutant deficient in ihk/irr displayed significantly reduced bacterial counts when compared to wild-type bacteria following infection of macrophages. The findings illustrate how gene expression of S. pyogenes during the intracellular life cycle is fine-tuned by temporal expression of specific two-component systems. PMID:22511985

  2. [Evaluation of rapid diagnostic kits for the detection of group A streptococcus to Streptococcus pyogenes and Streptococcus spp. with Lancefield's group A antigen].

    PubMed

    Mitsuno, Noriko; Hari, Tomohiro; Tamagawa, Nobuyoshi; Itoi, Juichi; Ikeda, Eiji; Hamasaki, Kazuko; Katsukawa, Chihiro; Okuyama, Michiko

    2006-11-01

    We studied the basic performance of eight rapid diagnostic kits for the detection of Group A streptococcus by immunochromatography under the same conditions. Kits were the; QuickVue Dipstick Strep A (Sumitomo Seiyaku Biomedical Co., Ltd.), TESTPACK Plus STREP A (ABBOTT JAPAN Co., Ltd), CLEAVIEW STREP A (Nihon Schering K. K.), QuickVue STREP A (Wako Pure Chemical Industries, Ltd), ImmunoCard STAT! STREP A (TFB, INC.), DIPSTICK 'Eiken' STREP A (Eiken Chemical Co., Ltd.), Rapid Testa Strep A (Daiichi Pure Chemical Co., Ltd.), and StatCheck Strep A (KAINOS Laboratories, Inc.). Four of these kits, i.e. QuickVue Dipstick Strep A, TESTPACK Plus STREP A, Rapid Testa Strep A, and StatCheck Strep A showed sensitivity at 1.0 x 10(5) CFU/mL (1.0 x 10(4)CFU/test) with all of S. pyogenes tested, while the Anginosus group and S. dysgalactiae subsp. equisimilis with Lancefield' s group A antigen showed sensitivity very similar to S. pyogenes. Of these strains, S. dysgalactiae subsp. equisimilis formed a beta-hemolytic colony resembling that of S. pyogenes on sheep blood agar, and was sensitive to bacitracin. It is thus indispensable to identify the colony using biochemical tests such as the PYR (pyrrolidonylarylamidase production) test. In using rapid diagnostic kits for the detection of Group A streptococcus, it is important to rule out the possibility of Group A streptococcus other than S. pyogenes in throats. Severe invasive group-G streptococcal infections are increasing recently. Concerning S. dysgalactiae subsp. equisimilis, it is especially important to conduct these identification tests. PMID:17176853

  3. Lactobacillus plantarum reduces Streptococcus pyogenes virulence by modulating the IL-17, IL-23 and Toll-like receptor 2/4 expressions in human epithelial cells.

    PubMed

    Rizzo, Antonietta; Losacco, Antonio; Carratelli, Caterina Romano; Domenico, Marina Di; Bevilacqua, Nazario

    2013-10-01

    Streptococcus pyogenes is a common colonizer of the mucosal layers in the mouth, nose, and pharynx but it is also a major Gram-positive human pathogen that causes infections ranging from pharyngitis to severe systemic diseases. The lactobacilli colonize the oral tracts and are known to protect against colonization by many pathogens. Epithelial cells participate in the innate host defense by expressing a variety of proinflammatory cytokines and TLRs in the interaction with microorganisms. The potentially probiotic strain Lactobacillus plantarum was investigated for its capacity to influence the innate immune response of HEp-2 and A549 epithelial cells to S. pyogenes infection. In both epithelial cell types, pre-treatment with L. plantarum showed inhibition of S. pyogenes growth and a greater decrease in IL-17 and IL-23 levels compared to the control. Pre-treatment with the anti-TLR2/4 antibody abolished the inhibitory effects of L. plantarum on IL-17 and IL-23 production following S. pyogenes infection, indicating that L. plantarum downregulates TLR2/4-dependent IL-17 and IL-23 production. Overall, our findings suggest that in epithelial cell cultures with S. pyogenes, cytokine responses are modulated by the presence of L. plantarum through the induction of TLR2/TLR4. PMID:23892030

  4. A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C.

    PubMed Central

    Mollick, J A; Miller, G G; Musser, J M; Cook, R G; Grossman, D; Rich, R R

    1993-01-01

    Streptococcus pyogenes (group A Streptococcus) has re-emerged in recent years as a cause of severe human disease. Because extracellular products are involved in streptococcal pathogenesis, we explored the possibility that a disease isolate expresses an uncharacterized superantigen. We screened culture supernatants for superantigen activity with a major histocompatibility complex class II-dependent T cell proliferation assay. Initial fractionation with red dye A chromatography indicated production of a class II-dependent T cell mitogen by a toxic shock-like syndrome (TSLS) strain. The amino terminus of the purified streptococcal superantigen was more homologous to the amino termini of staphylococcal enterotoxins B, C1, and C3 (SEB, SEC1, and SEC3), than to those of pyrogenic exotoxins A, B, C or other streptococcal toxins. The molecule, designated SSA, had the same pattern of class II isotype usage as SEB in T cell proliferation assays. However, it differed in its pattern of human T cell activation, as measured by quantitative polymerase chain reaction with V beta-specific primers. SSA activated human T cells that express V beta 1, 3, 15 with a minor increase of V beta 5.2-bearing cells, whereas SEB activated V beta 3, 12, 15, and 17-bearing T cells. Immunoblot analysis of 75 disease isolates from several localities detected SSA production only in group A streptococci, and found that SSA is apparently confined to only three clonal lineages as defined by multilocus enzyme electrophoresis typing. Isolates of one of these lineages, (electrophoretic type 2) are strongly associated with TSLS. The data identify SSA as a novel streptococcal superantigen that appears to be more related structurally to staphylococcal enterotoxins than to streptococcal exotoxins. Because abundant SSA production is apparently confined to only three streptococcal clonal lineages, the data also suggest that the SSA gene has only recently been acquired by S. pyogenes. Images PMID:8349810

  5. Comparative growth, cross stress resistance, transcriptomics of Streptococcus pyogenes cultured under low shear modeled microgravity and normal gravity.

    PubMed

    Kalpana, Duraisamy; Im, Chanki; Lee, Yang Soo

    2016-01-01

    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. PMID:26858535

  6. Comparative growth, cross stress resistance, transcriptomics of Streptococcus pyogenes cultured under low shear modeled microgravity and normal gravity

    PubMed Central

    Kalpana, Duraisamy; Im, Chanki; Lee, Yang Soo

    2015-01-01

    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. PMID:26858535

  7. Overexpression and Enzymatic Assessment of Antigenic Fragments of Hyaluronidase Recombinant Protein From Streptococcus pyogenes

    PubMed Central

    Sadoogh Abbasian, Shabnam; Ghaznavi Rad, Ehsanollah; Akbari, Neda; Zolfaghari, Mohammad Reza; pakzad, Iraj; Abtahi, Hamid

    2014-01-01

    Background: Hyaluronidase catalyzes the hydrolysis of hyaluronan polymers to N-acetyl-D-glucosamine and D-glucuronic acid. This enzyme is a dimer of identical subunits. Hyaluronidase has different pharmaceutical and medical applications. Previously, we produced a recombinant hyaluronidase antigenic fragment of Streptococcus pyogenes. Objectives: This study aimed to improve the protein production and purity of hyaluronidase recombinant protein from S. pyogenes. In addition, the enzymatic activity of this protein was investigated. Materials and Methods: The expression of hyaluronidase antigenic fragments was optimized using IPTG concentration, time of induction, temperature, culture, and absorbance of 0.6-0.8-1 at 600 nm. Afterwards, the expressed proteins were purified and the enzymatic activity was assessed by turbid metric method. Results: Data indicated that maximum protein is produced in OD = 0.8, 0.5 mM Isopropyl ?-D-1-thiogalactopyranoside (IPTG), 37C, NB 1.5x, without glucose, incubated for overnight. The enzymatic activity of the recombinant protein was similar to the commercial form of hyaluronidase. Conclusions: The results showed that an antigenic fragment of the recombinant hyaluronidase protein from S. pyogenes has a considerable enzymatic activity. It can be suggested to use it for medical purposes. In addition, applications of bioinformatics software would facilitate the production of a smaller protein with same antigenic properties and enzymatic activity. PMID:25789122

  8. Complete Genome Sequence of emm4 Streptococcus pyogenes MEW427, a Throat Isolate from a Child Meeting Clinical Criteria for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS)

    PubMed Central

    Jacob, Kristin M.; Spilker, Theodore; LiPuma, John J.; Dawid, Suzanne R.

    2016-01-01

    We report the complete genome assembly of the Streptococcus pyogenes type emm4 strain MEW427 (also referred to as strain UM001 in the Pediatric Acute-Onset Neuropsychiatric Syndrome [PANS] Research Consortium), a throat isolate from a child with acute-onset neuropsychiatric symptoms meeting clinical criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). The genome length is 1,814,455 bp with 38.51% G+C%. PMID:26988046

  9. Complete Genome Sequence of emm4 Streptococcus pyogenes MEW427, a Throat Isolate from a Child Meeting Clinical Criteria for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS).

    PubMed

    Jacob, Kristin M; Spilker, Theodore; LiPuma, John J; Dawid, Suzanne R; Watson, Michael E

    2016-01-01

    We report the complete genome assembly of the Streptococcus pyogenes type emm4 strain MEW427 (also referred to as strain UM001 in the Pediatric Acute-Onset Neuropsychiatric Syndrome [PANS] Research Consortium), a throat isolate from a child with acute-onset neuropsychiatric symptoms meeting clinical criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). The genome length is 1,814,455 bp with 38.51% G+C%. PMID:26988046

  10. Genome Sequence of a Nephritogenic and Highly Transformable M49 Strain of Streptococcus pyogenes?

    PubMed Central

    McShan, W. Michael; Ferretti, Joseph J.; Karasawa, Tadahiro; Suvorov, Alexander N.; Lin, Shaoping; Qin, Biafang; Jia, Honggui; Kenton, Steve; Najar, Fares; Wu, Hongmin; Scott, Julie; Roe, Bruce A.; Savic, Dragutin J.

    2008-01-01

    The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT type 3; emm pattern E), originally isolated from a case of acute post-streptococcal glomerulonephritis, is unusually competent for electrotransformation and has been used extensively as a model organism for both basic genetic and pathogenesis investigations. As with the previously sequenced S. pyogenes genomes, three unique prophages are a major source of genetic diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR) regions were present in the genome, providing genetic information on previous prophage encounters. A unique cluster of genes was found in the pathogenicity island-like emm region that included a novel Nudix hydrolase, and, further, this cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases eliminate potentially hazardous materials or prevent the unbalanced accumulation of normal metabolites; in bacteria, these enzymes may play a role in host cell invasion. Since M49 S. pyogenes strains have been known to be associated with skin infections, the Nudix hydrolase and its associated genes may have a role in facilitating survival in an environment that is more variable and unpredictable than the uniform warmth and moisture of the throat. The genome of NZ131 continues to shed light upon the evolutionary history of this human pathogen. Apparent horizontal transfer of genetic material has led to the existence of highly variable virulence-associated regions that are marked by multiple rearrangements and genetic diversification while other regions, even those associated with virulence, vary little between genomes. The genome regions that encode surface gene products that will interact with host targets or aid in immune avoidance are the ones that display the most sequence diversity. Thus, while natural selection favors stability in much of the genome, it favors diversity in these regions. PMID:18820018

  11. Frequency of Spontaneous Resistance to Peptide Deformylase Inhibitor GSK1322322 in Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae

    PubMed Central

    Ingraham, Karen; Huang, Jianzhong; McCloskey, Lynn; Rilling, Sarah; Windau, Anne; Pizzollo, Jason; Butler, Deborah; Aubart, Kelly; Miller, Linda A.; Zalacain, Magdalena; Holmes, David J.; O'Dwyer, Karen

    2015-01-01

    The continuous emergence of multidrug-resistant pathogenic bacteria is compromising the successful treatment of serious microbial infections. GSK1322322, a novel peptide deformylase (PDF) inhibitor, shows good in vitro antibacterial activity and has demonstrated safety and efficacy in human proof-of-concept clinical studies. In vitro studies were performed to determine the frequency of resistance (FoR) to this antimicrobial agent in major pathogens that cause respiratory tract and skin infections. Resistance to GSK1322322 occurred at high frequency through loss-of-function mutations in the formyl-methionyl transferase (FMT) protein in Staphylococcus aureus (4/4 strains) and Streptococcus pyogenes (4/4 strains) and via missense mutations in Streptococcus pneumoniae (6/21 strains), but the mutations were associated with severe in vitro and/or in vivo fitness costs. The overall FoR to GSK1322322 was very low in Haemophilus influenzae, with only one PDF mutant being identified in one of four strains. No target-based mutants were identified from S. pyogenes, and only one or no PDF mutants were isolated in three of the four S. aureus strains studied. In S. pneumoniae, PDF mutants were isolated from only six of 21 strains tested; an additional 10 strains did not yield colonies on GSK1322322-containing plates. Most of the PDF mutants characterized from those three organisms (35/37 mutants) carried mutations in residues at or in close proximity to one of three highly conserved motifs that are part of the active site of the PDF protein, with 30 of the 35 mutations occurring at position V71 (using the S. pneumoniae numbering system). PMID:26014938

  12. Frequency of Spontaneous Resistance to Peptide Deformylase Inhibitor GSK1322322 in Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae.

    PubMed

    Min, Sharon; Ingraham, Karen; Huang, Jianzhong; McCloskey, Lynn; Rilling, Sarah; Windau, Anne; Pizzollo, Jason; Butler, Deborah; Aubart, Kelly; Miller, Linda A; Zalacain, Magdalena; Holmes, David J; O'Dwyer, Karen

    2015-08-01

    The continuous emergence of multidrug-resistant pathogenic bacteria is compromising the successful treatment of serious microbial infections. GSK1322322, a novel peptide deformylase (PDF) inhibitor, shows good in vitro antibacterial activity and has demonstrated safety and efficacy in human proof-of-concept clinical studies. In vitro studies were performed to determine the frequency of resistance (FoR) to this antimicrobial agent in major pathogens that cause respiratory tract and skin infections. Resistance to GSK1322322 occurred at high frequency through loss-of-function mutations in the formyl-methionyl transferase (FMT) protein in Staphylococcus aureus (4/4 strains) and Streptococcus pyogenes (4/4 strains) and via missense mutations in Streptococcus pneumoniae (6/21 strains), but the mutations were associated with severe in vitro and/or in vivo fitness costs. The overall FoR to GSK1322322 was very low in Haemophilus influenzae, with only one PDF mutant being identified in one of four strains. No target-based mutants were identified from S. pyogenes, and only one or no PDF mutants were isolated in three of the four S. aureus strains studied. In S. pneumoniae, PDF mutants were isolated from only six of 21 strains tested; an additional 10 strains did not yield colonies on GSK1322322-containing plates. Most of the PDF mutants characterized from those three organisms (35/37 mutants) carried mutations in residues at or in close proximity to one of three highly conserved motifs that are part of the active site of the PDF protein, with 30 of the 35 mutations occurring at position V71 (using the S. pneumoniae numbering system). PMID:26014938

  13. Carrier state of Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara, Nepal

    PubMed Central

    Bhatta, Dharm Raj; Gokhale, Shishir; Sharma, Annavarapu Laxminarasimha; Gupta, Umesh; Gaur, Abhishek; Gowda, Supram; Raut, Shristi; Thapa, Sangeeta; Khadka, Rupendra

    2014-01-01

    Objective To determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae), Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children. Methods Specimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 102 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures. Results Potential pathogens isolated in our study were S. pneumoniae (14.7%), Staphylococcus aureus (12.7%), Corynebacterium diphtheriae (3.9%), Streptococcus pyogenes (3.9%) and Haemophilus influenzae (1.9%). Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73%) and resistance of Staphylococcus aureus to oxacillin (23%). Conclusions Pharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.

  14. Streptococcus pyogenes in the throat: a study in a small population, 1962-1975.

    PubMed Central

    Hope-Simpson, R. E.

    1981-01-01

    A general practice population of around 6700 was kept under clinical and laboratory surveillance from 1962 to 1975. Illnesses totalled 18703 in three morbidity classes: sore throat (Throats) 4451, acute febrile respiratory diseases (FRD) 4934, acute non-febrile respiratory diseases (Non-FRD) 9318. Specimens were examined for beta-haemolytic streptococci (BHS) from 37.1% of these illnesses: from Throats 33.3%, from FRD 67.8%, from Non-FRD 22.6%, and 515 specimens were collected from a miscellaneous ("Other') class consisting of healthy persons and ailments that could not have had a streptococcal component. Strains of BHS were isolated from 7448 specimens as follows: group A (Streptococcus pyogenes) 353, group C 36, group G 15, other groups 274. Group A strains were isolated from specimens at the following rates: Throats 16.7%, FRD 2.4%, Non-FRD 0.9%. Other 1.4%. The last two classes reflect the carrier rate in the general community, which must be deducted to obtain the streptococcal morbidity in the other classes. Carriers thus accounted for 6% of the strains isolated from the Throats class and for 42% of those from FRD illnesses. No consistent seasonal trend of prevalence was detected. Long-term fluctuations in prevalence over several years affected all groups and most group A serotypes. Serotyping was performed on 304 strains from 1963 to 1975. The commonest types found were T-types 4 and 12 and M-type 12. Immunity against re-infection by identical strains appeared to be fairly strong and also against heterotypic strains that shared a T-antigen, but little protection was conferred against re-infection by group A strains with no shared M- or T- antigen. R-28 antigen is considered here as a marker epidemiologically equivalent to an M-antigen. Epidemicity, as measured by a simple estimate of aggregation, appeared to be low and there were differences between and within serotypes. The infecting organism appeared to linger in the pharynx, sometimes for several months, after a streptococcal illness. PMID:7019317

  15. [Distribution of emm genotypes and antibiotic susceptibility of Streptococcus pyogenes strains: analogy with the vaccine in development].

    PubMed

    Arslan, U?ur; Orya??n, Erman; Eskin, Zeynep; Trk Da??, Hatice; F?nd?k, Duygu; Tuncer, Inci; Bozdo?an, Blent

    2013-04-01

    Streptococcus pyogenes is the most common bacterial pathogen causing pharyngotonsillitis, and also can lead to diseases such as otitis media, impetigo, necrotizing fasciitis, bacteremia, sepsis and toxic shock-like syndrome. M protein encoded by emm gene is an important virulence factor of S.pyogenes and it is used for genotyping in epidemiological studies. The aims of this study were to determine the M protein types of group A streptococci (GAS) by using emm gene sequence analysis method, to compare the M types in terms of analogy with the vaccine in development and to determine the antibiotic susceptibilities of the isolates. A total of 35 GAS strains isolated from various clinical specimens in our laboratory were included in the study. Strains growing in blood culture were considered as invasive, strains growing in throat and abscess cultures were considered as non-invasive. The isolates have been identified by conventional methods and 16S rRNA sequence analysis at species level. emm genotyping of strains identified as S.pyogenes, was performed by PCR method as proposed by the CDC. Amplicons were obtained and sequenced in 23 out of 35 isolates. The results were compared with CDC emm sequence database. Antibiotic susceptibility of the isolates was performed by agar dilution method and evaluated as recommended by CLSI. Twenty-three out of 35 isolates could be typed and 15 different emm genotypes were detected. The most common emm types were emm1 (22%), emm89 (13%), emm18 (9%) and emm19 (9%). The detection rate of other emm types (emm5, 12, 14, 17, 26, 29, 37, 74, 78, 92, 99) was 47%. Types emm1, 12, 19, 74, 89 and 99 were observed in strains isolated from blood cultures. It was detected that nine of the 15 (60%) emm types are within the contents of 26 valent vaccine (emm 1, 5, 12, 14, 18, 19, 29, 89, 92). It was also observed that 17 (74%) of the 23 cases were infected by vaccine types and the four emm types (emm1, 12, 19, 89) identified in blood samples were among the vaccine types. All of the strains were found susceptible to penicillin, ampicillin, erythromycin, lincomycin, gentamicin, chloramphenicol, vancomycin and linezolid, however six isolates were resistant to levofloxacin (MIC= 4 and 16 g/ml) and one isolate was resistant to tetracycline (MIC= 16 g/ml). In conclusion, this preliminary local study with limited number of invasive and non-invasive S.pyogenes isolates, emphasized the need for larger scale multi-center studies to determine the analogy and efficacy of the vaccine in development. PMID:23621731

  16. Structural Conservation, Variability, and Immunogenicity of the T6 Backbone Pilin of Serotype M6 Streptococcus pyogenes

    PubMed Central

    Moreland, Nicole J.; Loh, Jacelyn M.; Bell, Anita; Atatoa Carr, Polly; Proft, Thomas; Baker, Edward N.

    2014-01-01

    Group A streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen that causes a broad range of diseases ranging from acute pharyngitis to the poststreptococcal sequelae of acute rheumatic fever. GAS pili are highly diverse, long protein polymers that extend from the cell surface. They have multiple roles in infection and are promising candidates for vaccine development. This study describes the structure of the T6 backbone pilin (BP; Lancefield T-antigen) from the important M6 serotype. The structure reveals a modular arrangement of three tandem immunoglobulin-like domains, two with internal isopeptide bonds. The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. The T6 structure also highlights a conserved pilin core whose surface is decorated with highly variable loops and extensions. Comparison to other Gram-positive BPs shows that many of the largest variable extensions are found in conserved locations. Studies with sera from patients diagnosed with GAS-associated acute rheumatic fever showed that each of the three T6 domains, and the largest of the variable extensions (V8), are targeted by IgG during infection in vivo. Although the GAS BP show large variations in size and sequence, the modular nature of the pilus proteins revealed by the T6 structure may aid the future design of a pilus-based vaccine. PMID:24778112

  17. Structural conservation, variability, and immunogenicity of the T6 backbone pilin of serotype M6 Streptococcus pyogenes.

    PubMed

    Young, Paul G; Moreland, Nicole J; Loh, Jacelyn M; Bell, Anita; Atatoa Carr, Polly; Proft, Thomas; Baker, Edward N

    2014-07-01

    Group A streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen that causes a broad range of diseases ranging from acute pharyngitis to the poststreptococcal sequelae of acute rheumatic fever. GAS pili are highly diverse, long protein polymers that extend from the cell surface. They have multiple roles in infection and are promising candidates for vaccine development. This study describes the structure of the T6 backbone pilin (BP; Lancefield T-antigen) from the important M6 serotype. The structure reveals a modular arrangement of three tandem immunoglobulin-like domains, two with internal isopeptide bonds. The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. The T6 structure also highlights a conserved pilin core whose surface is decorated with highly variable loops and extensions. Comparison to other Gram-positive BPs shows that many of the largest variable extensions are found in conserved locations. Studies with sera from patients diagnosed with GAS-associated acute rheumatic fever showed that each of the three T6 domains, and the largest of the variable extensions (V8), are targeted by IgG during infection in vivo. Although the GAS BP show large variations in size and sequence, the modular nature of the pilus proteins revealed by the T6 structure may aid the future design of a pilus-based vaccine. PMID:24778112

  18. Streptococcus pyogenes Malate Degradation Pathway Links pH Regulation and Virulence

    PubMed Central

    Paluscio, Elyse

    2015-01-01

    The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression of maeP and maeE is induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI– mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP–, MaeK–, and MaeR– mutants were attenuated for virulence, whereas a MaeE– mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection. PMID:25583521

  19. Scrum kidney: epidemic pyoderma caused by a nephritogenic Streptococcus pyogenes in a rugby team.

    PubMed

    Ludlam, H; Cookson, B

    1986-08-01

    In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match. PMID:2874337

  20. [Susceptibility of Streptococcus pyogenes to macrolides and quinolones in Guadalajara, Spain].

    PubMed

    Rodrguez-Zurita, M E; Sols del Bao, S; Robres Guilln, P; Gonzlez Praetorius, A; Gimeno Fernndez, C; Prez Pomata, M T; Bisquert Santiago, J

    2003-03-01

    We carried out a retrospective study of the susceptibility of 104 Streptococcus pyogenes strains, which were isolated in 2000 and 2001 from clinical samples of different origins, to penicillin, erythromycin, clindamycin, ofloxacin and levofloxacin. The susceptibility testing was performed using the agar difusion method according to the guidelines of the NCCLS. All of the isolates showed susceptibility to penicillin and clindamycin. However, we detected 11 strains that were resistant to erythromycin (10.6%) and 4 strains resistant to ofloxacin (3.8%). We studied the resistance phenotypes of macrolides and lincosamides using erythromycin and clindamycin discs. Nine of the eleven strains that were resistant to erythromycin showed an M phenotype, while the remaining two showed inducible resistance to clindamycin, thus suggesting an MLS(B) inducible phenotype. No strains with constitutive resistance to erythromycin or clindamycin (MLS(B) constitutive phenotype) were identified. While penicillin is still uniformly active against S. pyogenes, in Guadalajara, there are 10.6% strains that are resistant to 14- and 15-atoms macrolides. PMID:12750759

  1. Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes Mprotein

    PubMed Central

    Lannergrd, Jonas; Kristensen, Bodil M; Gustafsson, Mattias C U; Persson, Jenny J; Norrby-Teglund, Anna; Stlhammar-Carlemalm, Margaretha; Lindahl, Gunnar

    2015-01-01

    The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S.pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack. PMID:26175306

  2. An improved SELEX technique for selection of DNA aptamers binding to M-type 11 of Streptococcus pyogenes.

    PubMed

    Hamula, Camille L A; Peng, Hanyong; Wang, Zhixin; Tyrrell, Gregory J; Li, Xing-Fang; Le, X Chris

    2016-03-15

    Streptococcus pyogenes is a clinically important pathogen consisting of various serotypes determined by different M proteins expressed on the cell surface. The M type is therefore a useful marker to monitor the spread of invasive S. pyogenes in a population. Serotyping and nucleic acid amplification/sequencing methods for the identification of M types are laborious, inconsistent, and usually confined to reference laboratories. The primary objective of this work is to develop a technique that enables generation of aptamers binding to specific M-types of S. pyogenes. We describe here an in vitro technique that directly used live bacterial cells and the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) strategy. Live S. pyogenes cells were incubated with DNA libraries consisting of 40-nucleotides randomized sequences. Those sequences that bound to the cells were separated, amplified using polymerase chain reaction (PCR), purified using gel electrophoresis, and served as the input DNA pool for the next round of SELEX selection. A specially designed forward primer containing extended polyA20/5Sp9 facilitated gel electrophoresis purification of ssDNA after PCR amplification. A counter-selection step using non-target cells was introduced to improve selectivity. DNA libraries of different starting sequence diversity (10(16) and 10(14)) were compared. Aptamer pools from each round of selection were tested for their binding to the target and non-target cells using flow cytometry. Selected aptamer pools were then cloned and sequenced. Individual aptamer sequences were screened on the basis of their binding to the 10 M-types that were used as targets. Aptamer pools obtained from SELEX rounds 5-8 showed high affinity to the target S. pyogenes cells. Tests against non-target Streptococcus bovis, Streptococcus pneumoniae, and Enterococcus species demonstrated selectivity of these aptamers for binding to S. pyogenes. Several aptamer sequences were found to bind preferentially to the M11 M-type of S. pyogenes. Estimated binding dissociation constants (Kd) were in the low nanomolar range for the M11 specific sequences; for example, sequence E-CA20 had a Kd of 7±1nM. These affinities are comparable to those of a monoclonal antibody. The improved bacterial cell-SELEX technique is successful in generating aptamers selective for S. pyogenes and some of its M-types. These aptamers are potentially useful for detecting S. pyogenes, achieving binding profiles of the various M-types, and developing new M-typing technologies for non-specialized laboratories or point-of-care testing. PMID:26678795

  3. Functional and Structural Properties of a Novel Protein and Virulence Factor (Protein sHIP) in Streptococcus pyogenes *

    PubMed Central

    Wisniewska, Magdalena; Happonen, Lotta; Kahn, Fredrik; Varjosalo, Markku; Malmstrm, Lars; Rosenberger, George; Karlsson, Christofer; Cazzamali, Giuseppe; Pozdnyakova, Irina; Frick, Inga-Maria; Bjrck, Lars; Streicher, Werner; Malmstrm, Johan; Wikstrm, Mats

    2014-01-01

    Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment, enabling bacterial interactions with the host. In the present study, we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice with a non-virulent strain. Particularly, one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal histidine-rich glycoprotein-interacting protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP suggest a role for the protein in S. pyogenes pathogenesis. PMID:24825900

  4. Molecular modeling on streptolysin-O of multidrug resistant Streptococcus pyogenes and computer aided screening and in vitro assay for novel herbal inhibitors.

    PubMed

    Skariyachan, Sinosh; Narayan, Naik Sowmyalaxmi; Aggimath, Tejaswini S; Nagaraj, Sushmitha; Reddy, Monika S; Narayanappa, Rajeswari

    2014-03-01

    Streptococcus pyogenes is a notorious pathogenic bacterium which causes various human diseases ranging from localized infections to life threatening invasive diseases. Streptolysin-O (SLO), pore-forming thiol-activated cytolysin, is the major virulent factor for streptococcal infections. Present therapies against streptococcal infections are limited as most of the strains have developed multi-drug resistance to present generation of drugs. Hence, there is a need for alternative therapeutic substances. Structure based virtual screening is a novel platform to select lead molecules with better pharmacokinetic properties. The 3D structure of SLO (not available in native form), essential for such studies, was computationally generated and this homology model was used as probable drug target. Based on literature survey, several phytoligands from 25 medicinal plants were selected. Out of these, leads from 11 plants showed better pharmacokinetic properties. The best lead molecules were screened based on computer aided drug likeness and pharmacokinetic predictions. The inhibitory properties of selected herbal leads against SLO were studied by molecular docking. An in vitro assay was further carried out and variations observed were found to be significant (p<0.05). Antibiotic sensitivity testing was also performed with the clinical strain of Streptococcus pyogenes with conventional drugs. The clinical strain showed multi-drug resistance to conventional drugs. Our study revealed that numerous phytoligands have better inhibitory properties towards the toxin. We noticed that incorporation of selected herbal extracts in blood agar medium showed significant reduction in hemolysis (MIC 300μl/plate), indicating inhibition of SLO. Furthermore, the butanol extracts of selected herbal preparation based on computer aided screening showed significant inhibitory properties at 250 mcg/disc concentration. We also noticed that selected herbal formulations have better antimicrobial properties at MIC range of 300- 400μl. Hence, our study suggests that these herbal extracts have better inhibitory properties against the toxin as well as drug resistant Streptococcus pyogenes. PMID:24694051

  5. Susceptibilities of Streptococcus pyogenes and Streptococcus pneumoniae to macrolides and telithromycin: data from an Italian multicenter study.

    PubMed

    Mazzariol, A; Koncan, R; Bahar, G; Cornaglia, G

    2007-10-01

    687 isolates of Streptococcus pyogenes and 600 isolates of Streptococcus pneumoniae , isolated over the period 2002-2003 from specimens of different human origin obtained in 16 different Italian centres, were assayed for their susceptibilities to different macrolides and to telithromycin, and were investigated by PCR to detect their different erythromycin resistance genes. 25.5% of the S. pyogenes isolates proved resistant to erythromycin, as well as to clarithromycin and azithromycin. 6.6% of the isolates proved non-susceptible to clindamycin. 4.9% of the isolates were non-susceptible to telithromycin. 22.3% of all erythromycin-resistant isolates exhibited cMLS B resistance, 50.3% iMLS B resistance, and 27.4% Mtype resistance. All cMLS B strains had the erm(B) gene, all M strains had the mef (A) gene, and no resistance genes were found in the erythromycin-susceptible strains. Roughly one quarter of the iMLS(B) strains had erm(A) and roughly three quarters erm(B). 35.2% of the S. pneumoniae isolates proved resistant to erythromycin, and virtually all of them also proved resistant to clarithromycin and azithromycin, too. Only 6.0% of the pneumococcal isolates were resistant to penicillin and a further 11.0% were intermediate. Only 0.2% of the isolates were nonsusceptible to telithromycin. 65.9% of all erythromycin-resistant S. pneumoniae isolates had cMLS B resistance, 18.0% had iMLS B resistance, and 16.1% had M-type resistance. All the MLS B-resistant isolates had an erm(B) gene, and all the M-type isolates had a mef gene. We conclude that macrolide resistance of streptococci still persists in Italy with incidences as high as 40%, more often than not being characterised by the MLS B phenotype. The ketolide telithromycin, structurally related to macrolides and most likely to substitute for them in a number of clinical uses, is confirmed as being extremely active even against recent clinical streptococcal isolates. PMID:18073148

  6. Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes

    PubMed Central

    Le Breton, Yoann; Belew, Ashton T.; Valdes, Kayla M.; Islam, Emrul; Curry, Patrick; Tettelin, Hervé; Shirtliff, Mark E.; El-Sayed, Najib M.; McIver, Kevin S.

    2015-01-01

    Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways, and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci. PMID:25996237

  7. PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing.

    PubMed

    Wilkening, Reid V; Chang, Jennifer C; Federle, Michael J

    2016-01-01

    Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg(2+) and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles. PMID:26418177

  8. Rapid identification of the animal pathogens Streptococcus uberis and Arcanobacterium pyogenes by fluorescence in situ hybridization (FISH).

    PubMed

    Werckenthin, Christiane; Gey, Annerose; Straubinger, Reinhard K; Poppert, Sven

    2012-05-01

    Fluorescence in situ hybridization (FISH) has been reported to be an easy and rapid identification method for many human pathogens, but applications for common veterinary pathogens are lacking. Gene probes for FISH of the animal pathogens Streptococcus uberis and Arcanobacterium pyogenes were designed to provide probes for a specific identification of these bacteria from cultures. Specific FISH probes for these species have so far not been published. Both probes recognized all isolates of the target species correctly. With the S. uberis probe SUB 196 no false-positive results were obtained for reference strains as well as for clinical isolates. Probe APYO 183 for A. pyogenes produced false-positive reactions with so far rarely described Arcanobacterium species from animals at standard hybridization conditions. In order to avoid any incorrect classifications of microorganisms as A. pyogenes, two non-labelled competitor probes were designed and successfully evaluated. PMID:22033042

  9. Complete Genome Sequence of Streptococcus pyogenes emm28 Clinical Isolate M28PF1, Responsible for a Puerperal Fever

    PubMed Central

    Longo, Magalie; De Jode, Mathieu; Plainvert, Cline; Weckel, Antonin; Hua, Anna; Chteau, Alice; Glaser, Philippe; Poyart, Claire

    2015-01-01

    We report the sequence of the Streptococcus pyogenes emm28 strain M28PF1, isolated from a patient with postpartum endometritis. The M28 protein is smaller than that of MGAS6180 (NC_007296.1). Furthermore, the 1,896,976-bp-long chromosome presents, compared to that of MGAS6180, an inversion between the two comX genes. PMID:26184934

  10. Molecular characterization of macrolide resistant Streptococcus pyogenes isolates from pharyngitis patients in Serbia.

    PubMed

    Opavski, Natasa; Gajic, Ina; Borek, Anna L; Obsza?ska, Katarzyna; Stanojevic, Maja; Lazarevic, Ivana; Ranin, Lazar; Sitkiewicz, Izabela; Mijac, Vera

    2015-07-01

    A steady increase in macrolide resistance in Streptococcus pyogenes, group A streptococci (GAS) was reported in Serbia during 2004-2009 (9.9%). However, there are no data on the molecular epidemiology of pharyngeal macrolide resistance GAS (MRGAS) isolates. Therefore, the aims of this first nationwide study were to examine the prevalence of macrolide resistance in Serbian GAS and to determine their resistance phenotypes, genotypes and clonal relationships. Overall 3893 non-duplicate pharyngeal S. pyogenes isolates from outpatients with GAS infection were collected throughout country during 2008 and 2009. Among 486 macrolide resistant pharyngeal isolates collected, 103 were further characterized. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion test and PCR, respectively. Strain relatedness was determined by emm typing, multilocus sequence typing (MLST), multilocus variable tandem repeat analysis (MLVA), phage profiling (PP) and virulence factor profiling (VFP). Overall, macrolide resistance among GAS isolates in Serbia was 12.5%. M phenotype was the most common (71.8%), followed by iMLS (18.4%) and cMLS (9.7%). Three clonal complexes--emm75/mefA/ST49, emm12/mefA/ST36 and emm77/ermA/tetO/ST63 comprised over 90% of the tested strains. Although MLVA, PP and VFP distinguished 10, 20 and 12 different patterns, respectively, cluster analysis disclosed only small differences between strains which belonged to the same emm/ST type. Our data indicate dominance of three major internationally widely disseminated macrolide resistant clones and a high genetic homogeneity among the Serbian MRGAS population. Continued surveillance of macrolide resistance and clonal composition in MRGAS in Serbia in future is necessary to determine stability of MRGAS clones and to guide therapy strategies. PMID:25976381

  11. Transcription of the Streptococcus pyogenes hyaluronic acid capsule biosynthesis operon is regulated by previously unknown upstream elements.

    PubMed

    Falaleeva, Marina; Zurek, Oliwia W; Watkins, Robert L; Reed, Robert W; Ali, Hadeel; Sumby, Paul; Voyich, Jovanka M; Korotkova, Natalia

    2014-12-01

    The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of hasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of hasS or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through, hasA transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence. PMID:25287924

  12. Biochemical and biological activity of arginine deiminase from Streptococcus pyogenes M22.

    PubMed

    Starikova, Eleonora A; Sokolov, Alexey V; Vlasenko, Anna Yu; Burova, Larisa A; Freidlin, Irina S; Vasilyev, Vadim B

    2016-04-01

    Streptococcus pyogenes (group A Streptococcus; GAS) is an important gram-positive extracellular bacterial pathogen responsible for a number of suppurative infections. This micro-organism has developed complex virulence mechanisms to avoid the host's defenses. We have previously reported that SDSC from GAS type M22 causes endothelial-cell dysfunction, and inhibits cell adhesion, migration, metabolism, and proliferation in a dose-dependent manner, without affecting cell viability. This work aimed to isolate and characterize a component from GAS type M22 supernatant that suppresses the proliferation of endothelial cells (EA.hy926). In the process of isolating a protein possessing antiproliferative activity we identified arginine deiminase (AD). Further study showed that this enzyme is most active at pH 6.8. Calculating Km and Vmax gave the values of 0.67 mmol·L(-1) and 42 s(-1), respectively. A distinctive feature of AD purified from GAS type M22 is that its optimum activity and the maximal rate of the catalytic process is close to neutral pH by comparison with enzymes from other micro-organisms. AD from GAS type M22 suppressed the proliferative activity of endothelial cells in a dose-dependent mode. At the same time, in the presence of AD, the proportion of cells in G0/G1 phase increased. When l-Arg was added at increasing concentrations to the culture medium containing AD (3 μg·mL(-1)), the enzyme's capacity to inhibit cell proliferation became partially depressed. The proportion of cells in phases S/G2 increased concomitantly, although the cells did not fully recover their proliferation activity. This suggests that AD from GAS type M22 has potential for the suppression of excessive cell proliferation. PMID:26695833

  13. Distinct Time-Resolved Roles for Two Catabolite-Sensing Pathways during Streptococcus pyogenes Infection?

    PubMed Central

    Kietzman, Colin C.; Caparon, Michael G.

    2011-01-01

    Many Gram-positive pathogens link the expression of virulence genes to the presence of carbon source substrates using overlapping pathways for global control of carbon catabolite regulation. However, how these pathways are integrated to control the behavior of the transcriptome in time- and compartment-specific patterns is typically not well understood. In the present study, global transcriptome profiling was used to determine the extent to which glucose alters gene expression in Streptococcus pyogenes (group A streptococcus) and the contributions of the CcpA and LacD.1 catabolite control pathways to the regulation of this response in vitro. This analysis revealed that the expression of as many as 15% of the genes examined was regulated and that CcpA and LacD.1 together contribute to the regulation of 60% of this subset. However, numerous patterns were observed, including both CcpA- and LacD.1-specific and independent regulation, coregulation, and regulation of genes by these pathways independently of glucose. In addition, CcpA and LacD.1 had antagonistic effects on most coregulated genes. To resolve the roles of these regulators during infection, the expression of selected transcripts representative of different regulatory patterns was examined in a murine model of soft tissue infection. This revealed distinct patterns of misregulation with respect to time in CcpA? versus LacD.1? mutants. Taken together, these data support an important role for carbohydrate in the regulation of the transcriptome in tissue and suggest that the CcpA and LacD.1 pathways are organized to function at different times during the course of an infection. PMID:21098101

  14. Involvement of T6 Pili in Biofilm Formation by Serotype M6 Streptococcus pyogenes

    PubMed Central

    Kimura, Keiji Richard; Nakata, Masanobu; Sumitomo, Tomoko; Kreikemeyer, Bernd; Podbielski, Andreas; Terao, Yutaka

    2012-01-01

    The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections. PMID:22155780

  15. Co-Infection of Rickettsia rickettsii and Streptococcus pyogenes: Is Fatal Rocky Mountain Spotted Fever Underdiagnosed?

    PubMed Central

    Raczniak, Gregory A.; Kato, Cecilia; Chung, Ida H.; Austin, Amy; McQuiston, Jennifer H.; Weis, Erica; Levy, Craig; Carvalho, Maria da Gloria S.; Mitchell, Audrey; Bjork, Adam; Regan, Joanna J.

    2014-01-01

    Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections. PMID:25331804

  16. Preparation and characterization of monomers to tetramers of a collagen-like domain from Streptococcus pyogenes

    PubMed Central

    Peng, Yong Y; Stoichevska, Violet; Howell, Linda; Madsen, Soren; Werkmeister, Jerome A; Dumsday, Geoff J; Ramshaw, John AM

    2014-01-01

    The collagen like domain Scl2 from Streptococcus pyogenes has been proposed as a potential biomedical material. It is non-cytotoxic and non-immunogenic and can be prepared in good yield in fermentation. The Scl2 collagen domain is about a quarter of the length, 234 residues, of the main collagen type, mammalian type I collagen (1014 residues) that is currently used in biomedical devices. In the present study we have made constructs comprising 1 to 4 copies of the Scl2 collagen domain, plus these same constructs with a CysCys sequence at the C-terminal, analogous to that found in mammalian type III collagens. The yields of these constructs were examined from 2 L fermentation studies. The yields of both series declined with increasing size. Circular dichroism showed that the addition of further collagen domains did not lead to a change in the melting temperature compared to the monomer domain. Addition of the CysCys sequence led to a small additional stabilization of about 2-3C for the monomer construct when the folding (V) domain was present. PMID:25482084

  17. Inducer expulsion in Streptococcus pyogenes: properties and mechanism of the efflux reaction

    SciTech Connect

    Sutrina, S.L.; Reizer, J.; Saier, M.H Jr.

    1988-04-01

    Expulsion of preaccumulated methyl-..beta..-D-thiogalactoside-phosphate (TMG-P) from Streptococcus pyogenes is a two-step process comprising intracellular dephosphorylation of TMG-P followed by rapid efflux of the intracellularly formed free galactoside. The present study identifies the mechanism and the order and characterizes the temperature dependency of the efflux step. Unidirectional efflux of the intracellularly formed (/sup 14/C)TMG was only slightly affected when measured in the presence of unlabeled TMG (25 to 400 mM) in the extracellular medium. In contrast, pronounced inhibition of net efflux was observed in the presence of relatively low concentrations (1 to 16 mM) of extracellular (/sup 14/C)TMG. Since net efflux was nearly arrested when the external concentration of (/sup 14/C)TMG approached the intracellular concentration of this sugar, we propose that a facilitated diffusion mechanism is responsible for efflux and equilibration of TMG between the intracellular and extracellular milieus. The exit reaction was markedly dependent upon temperature, exhibited a high energy of activation (23 kcal (ca. 96 kJ) per mol), and followed first-order kinetics, indicating that the permease mediating this efflux was not saturated under the conditions of expulsion employed.

  18. Kinetic and Structural Characterization for Cofactor Preference of Succinic Semialdehyde Dehydrogenase from Streptococcus pyogenes

    PubMed Central

    Jang, Eun Hyuk; Ah Park, Seong; Min Chi, Young; Lee, Ki Seog

    2014-01-01

    The ?-Aminobutyric acid (GABA) that is found in prokaryotic and eukaryotic organisms has been used in various ways as a signaling molecule or a significant component generating metabolic energy under conditions of nutrient limitation or stress, through GABA catabolism. Succinic semialdehyde dehydrogenase (SSADH) catalyzes the oxidation of succinic semialdehyde to succinic acid in the final step of GABA catabolism. Here, we report the catalytic properties and two crystal structures of SSADH from Streptococcus pyogenes (SpSSADH) regarding its cofactor preference. Kinetic analysis showed that SpSSADH prefers NADP+ over NAD+ as a hydride acceptor. Moreover, the structures of SpSSADH were determined in an apo-form and in a binary complex with NADP+ at 1.6 and 2.1 resolutions, respectively. Both structures of SpSSADH showed dimeric conformation, containing a single cysteine residue in the catalytic loop of each subunit. Further structural analysis and sequence comparison of SpSSADH with other SSADHs revealed that Ser158 and Tyr188 in SpSSADH participate in the stabilization of the 2-phosphate group of adenine-side ribose in NADP+. Our results provide structural insights into the cofactor preference of SpSSADH as the gram-positive bacterial SSADH. PMID:25256219

  19. Streptococcus pyogenes infection of tonsil explants is associated with a human ?-defensin 1 response from control but not recurrent acute tonsillitis patients.

    PubMed

    Bell, S; Howard, A; Wilson, J A; Abbot, E L; Smith, W D; Townes, C L; Hirst, B H; Hall, J

    2012-06-01

    Host defence peptides (HDP), including the defensins and hCAP-18, function as part of the innate immune defences, protecting the host epithelia from microbial attachment and invasion. Recurrent acute tonsillitis (RAT), in which patients suffer repeated symptomatic tonsil infections, is linked to Streptococcus pyogenes, a group A streptococcus, and may reflect the impaired expression of such peptides. To address this, the defensin and hCAP-18 messenger RNA expression profiles of 54 tonsils excised from control and RAT patients undergoing tonsillectomy were quantified and compared. Marked variation in expression was observed between individuals from the two groups, but statistically no significant differences were identified, suggesting that at the time of surgery the tonsil epithelial HDP barrier was not compromised in RAT subjects. Surgical removal of the tonsils occurs in a quiescent phase of disease, and so to assess the effects of an active bacterial infection, HaCaT cells an in vitro model of the tonsil epithelium, and explants of patient tonsils maintained in vitro were challenged with S. pyogenes. The HaCaT data supported the reduced expression of hCAP-18/LL-37, human ?-defensin 1 (HBD1;P < 0.01) and HBD2 (P < 0.05), consistent with decreased protection of the epithelial barrier. The tonsil explant data, although not as definitive, showed similar trends apart from HBD1 expression, which in the control tonsils but not the RAT patient tonsils was characterized by increased expression (P < 0.01). These data suggest that in vivo HBD1 may play a critical role in protecting the tonsil epithelia from S. pyogenes. PMID:22520386

  20. Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system.

    PubMed Central

    Sutcliffe, J; Tait-Kamradt, A; Wondrack, L

    1996-01-01

    Macrolide-resistant Streptococcus pyogenes isolates from Finland, Australia, and the United Kingdom and, more recently, Streptococcus pneumoniae and S. pyogenes strains from the United States were shown to have an unusual resistance pattern to macrolides, lincosamides, and streptogramin B antibiotics. This pattern, referred to as M resistance, consists of susceptibility to clindamycin and streptogramin B antibiotics but resistance to 14- and 15-membered macrolides. An evaluation of the macrolide-lincosamide-streptogramin B resistance phenotypes among our streptococcal strains collected from 1993 to 1995 suggested that this unusual resistance pattern is not rare. Eighty-five percent (n = 66) of the S. pneumoniae and 75% (n = 28) of the S. pyogenes strains in our collection had an M phenotype. The mechanism of M resistance was not mediated by target modification, as isolated ribosomes from a pneumococcal strain bearing the M phenotype were fully sensitive to erythromycin. Further, the presence of an erm methylase was excluded with primers specific for an erm consensus sequence. However, results of studies that determined the uptake and incorporation of radiolabeled erythromycin into cells were consistent with the presence of a macrolide efflux determinant. The putative efflux determinant in streptococci seems to be distinct from the multicomponent macrolide efflux system in coagulase-negative staphylococci. The recognition of the prevalence of the M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice. PMID:8843287

  1. Enzyme-linked immunosorbent assay for detection of type A streptococcal exotoxin: kinetics and regulation during growth of Streptococcus pyogenes.

    PubMed Central

    Houston, C W; Ferretti, J J

    1981-01-01

    We describe the detection and quantitation of type A streptococcal exotoxin (erythrogenic toxin, streptococcal pyrogenic exotoxin) by an enzyme-linked immunosorbent assay. This sensitive and specific technique detected microgram amounts of type A exotoxin and was useful for studying the kinetics and regulation of type A exotoxin production during the growth of Streptococcus pyogenes NY5. Maximum production of type A exotoxin was observed during the mid-log phase of growth, similar to the production of other streptococcal extracellular products. When S. pyogenes NY5 was grown at 42 degrees C, decreases in both growth and type A exotoxin production were observed. The results obtained when we studied the influence of nutrient additives and metal ions on the production of type A exotoxin led to the conclusion that none of these factors significantly affected type A exotoxin synthesis and that regulation was constitutive. Images PMID:7026447

  2. Tn5253 family integrative and conjugative elements carrying mef(I) and catQ determinants in Streptococcus pneumoniae and Streptococcus pyogenes.

    PubMed

    Mingoia, Marina; Morici, Eleonora; Morroni, Gianluca; Giovanetti, Eleonora; Del Grosso, Maria; Pantosti, Annalisa; Varaldo, Pietro E

    2014-10-01

    The linkage between the macrolide efflux gene mef(I) and the chloramphenicol inactivation gene catQ was first described in Streptococcus pneumoniae (strain Spn529), where the two genes are located in a module designated IQ element. Subsequently, two different defective IQ elements were detected in Streptococcus pyogenes (strains Spy029 and Spy005). The genetic elements carrying the three IQ elements were characterized, and all were found to be Tn5253 family integrative and conjugative elements (ICEs). The ICE from S. pneumoniae (ICESpn529IQ) was sequenced, whereas the ICEs from S. pyogenes (ICESpy029IQ and ICESpy005IQ, the first Tn5253-like ICEs reported in this species) were characterized by PCR mapping, partial sequencing, and restriction analysis. ICESpn529IQ and ICESpy029IQ were found to share the intSp 23FST81 integrase gene and an identical Tn916 fragment, whereas ICESpy005IQ has int5252 and lacks Tn916. All three ICEs were found to lack the linearized pC194 plasmid that is usually associated with Tn5253-like ICEs, and all displayed a single copy of a toxin-antitoxin operon that is typically contained in the direct repeats flanking the excisable pC194 region when this region is present. Two different insertion sites of the IQ elements were detected, one in ICESpn529IQ and ICESpy029IQ, and another in ICESpy005IQ. The chromosomal integration of the three ICEs was site specific, depending on the integrase (intSp 23FST81 or int5252). Only ICESpy005IQ was excised in circular form and transferred by conjugation. By transformation, mef(I) and catQ were cotransferred at a high frequency from S. pyogenes Spy005 and at very low frequencies from S. pneumoniae Spn529 and S. pyogenes Spy029. PMID:25070090

  3. Structure and Interactions of a Dimeric Variant of sHIP, a Novel Virulence Determinant of Streptococcus pyogenes.

    PubMed

    Diehl, Carl; Wisniewska, Magdalena; Frick, Inga-Maria; Streicher, Werner; Bjrck, Lars; Malmstrm, Johan; Wikstrm, Mats

    2016-01-01

    Streptococcus pyogenes is one of the most significant bacterial pathogens in the human population mostly causing superficial and uncomplicated infections (pharyngitis and impetigo) but also invasive and life-threatening disease. We have previously identified a virulence determinant, protein sHIP, which is secreted at higher levels by an invasive compared to a non-invasive strain of S. pyogenes. The present work presents a further characterization of the structural and functional properties of this bacterial protein. Biophysical and structural studies have shown that protein sHIP forms stable tetramers both in the crystal and in solution. The tetramers are composed of four helix-loop-helix motifs with the loop regions connecting the helices displaying a high degree of flexibility. Owing to interactions at the tetramer interface, the observed tetramer can be described as a dimer of dimers. We identified three residues at the tetramer interface (Leu84, Leu88, Tyr95), which due to largely non-polar side-chains, could be important determinants for protein oligomerization. Based on these observations, we produced a sHIP variant in which these residues were mutated to alanines. Biophysical experiments clearly indicated that the sHIP mutant appear only as dimers in solution confirming the importance of the interfacial residues for protein oligomerisation. Furthermore, we could show that the sHIP mutant interacts with intact histidine-rich glycoprotein (HRG) and the histidine-rich repeats in HRG, and inhibits their antibacterial activity to the same or even higher extent as compared to the wild type protein sHIP. We determined the crystal structure of the sHIP mutant, which, as a result of the high quality of the data, allowed us to improve the existing structural model of the protein. Finally, by employing NMR spectroscopy in solution, we generated a model for the complex between the sHIP mutant and an HRG-derived heparin-binding peptide, providing further molecular details into the interactions involving protein sHIP. PMID:26903974

  4. Structure and Interactions of a Dimeric Variant of sHIP, a Novel Virulence Determinant of Streptococcus pyogenes

    PubMed Central

    Diehl, Carl; Wisniewska, Magdalena; Frick, Inga-Maria; Streicher, Werner; Björck, Lars; Malmström, Johan; Wikström, Mats

    2016-01-01

    Streptococcus pyogenes is one of the most significant bacterial pathogens in the human population mostly causing superficial and uncomplicated infections (pharyngitis and impetigo) but also invasive and life-threatening disease. We have previously identified a virulence determinant, protein sHIP, which is secreted at higher levels by an invasive compared to a non-invasive strain of S. pyogenes. The present work presents a further characterization of the structural and functional properties of this bacterial protein. Biophysical and structural studies have shown that protein sHIP forms stable tetramers both in the crystal and in solution. The tetramers are composed of four helix-loop-helix motifs with the loop regions connecting the helices displaying a high degree of flexibility. Owing to interactions at the tetramer interface, the observed tetramer can be described as a dimer of dimers. We identified three residues at the tetramer interface (Leu84, Leu88, Tyr95), which due to largely non-polar side-chains, could be important determinants for protein oligomerization. Based on these observations, we produced a sHIP variant in which these residues were mutated to alanines. Biophysical experiments clearly indicated that the sHIP mutant appear only as dimers in solution confirming the importance of the interfacial residues for protein oligomerisation. Furthermore, we could show that the sHIP mutant interacts with intact histidine-rich glycoprotein (HRG) and the histidine-rich repeats in HRG, and inhibits their antibacterial activity to the same or even higher extent as compared to the wild type protein sHIP. We determined the crystal structure of the sHIP mutant, which, as a result of the high quality of the data, allowed us to improve the existing structural model of the protein. Finally, by employing NMR spectroscopy in solution, we generated a model for the complex between the sHIP mutant and an HRG-derived heparin-binding peptide, providing further molecular details into the interactions involving protein sHIP. PMID:26903974

  5. The Crystal Structure of Streptococcus pyogenes Uridine Phosphorylase Reveals a Distinct Subfamily of Nucleoside Phosphorylases

    SciTech Connect

    Tran, Timothy H.; Christoffersen, S.; Allan, Paula W.; Parker, William B.; Piskur, Jure; Serra, I.; Terreni, M.; Ealick, Steven E.

    2011-09-20

    Uridine phosphorylase (UP), a key enzyme in the pyrimidine salvage pathway, catalyzes the reversible phosphorolysis of uridine or 2'-deoxyuridine to uracil and ribose 1-phosphate or 2'-deoxyribose 1-phosphate. This enzyme belongs to the nucleoside phosphorylase I superfamily whose members show diverse specificity for nucleoside substrates. Phylogenetic analysis shows Streptococcus pyogenes uridine phosphorylase (SpUP) is found in a distinct branch of the pyrimidine subfamily of nucleoside phosphorylases. To further characterize SpUP, we determined the crystal structure in complex with the products, ribose 1-phosphate and uracil, at 1.8 {angstrom} resolution. Like Escherichia coli UP (EcUP), the biological unit of SpUP is a hexamer with an ?/? monomeric fold. A novel feature of the active site is the presence of His169, which structurally aligns with Arg168 of the EcUP structure. A second active site residue, Lys162, is not present in previously determined UP structures and interacts with O2 of uracil. Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is {approx}7-fold more efficient than SpUP. Biochemical studies of SpUP mutants showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that the negative charge in the transition state resides mostly on uracil O2. This is in contrast to EcUP for which transition state stabilization occurs mostly at O4.

  6. CcpA and LacD.1 Affect Temporal Regulation of Streptococcus pyogenes Virulence Genes ?

    PubMed Central

    Kietzman, Colin C.; Caparon, Michael G.

    2010-01-01

    Production of H2O2 follows a growth phase-dependent pattern that mimics that of many virulence factors of Streptococcus pyogenes. To gain greater insight into mechanisms coupling virulence factor expression to growth phase, we investigated the molecular basis for H2O2 generation and its regulation. Deletion of the gene encoding lactate oxidase (lctO) or culture in the presence of glucose eliminated H2O2 production, implicating carbohydrate regulation of lctO as a key element of growth phase control. In examining known carbohydrate-responsive regulators, deletion of the gene encoding CcpA but not that encoding LacD.1 resulted in both derepression and an uncoupling of lctO transcription from its growth phase pattern. Expanding this analysis to additional virulence factors demonstrated both negative (cfa, encoding CAMP factor) and positive (speB, encoding a cysteine protease) regulation by CcpA and that CcpA mutants were highly cytotoxic for cultured macrophages. This latter property resulted from enhanced transcription of the streptolysin S biogenesis operon. Examination of CcpA-promoter interactions using a DNA pull-down assay mimicking physiological conditions showed direct binding to the promoters of lctO and speB but not those of sagA. CcpA but not LacD.1 mutants were attenuated in a murine model of soft-tissue infection, and analysis of gene expression in infected tissue indicated that CcpA mutants had altered expression of lctO, cfa, and speB but not the indirectly regulated sagA gene. Taken together, these data show that CcpA regulates virulence genes via at least three distinct mechanisms and that disruption of growth phase regulation alters transcriptional patterns in infected tissues. PMID:19841076

  7. Protective mechanisms of respiratory tract Streptococci against Streptococcus pyogenes biofilm formation and epithelial cell infection.

    PubMed

    Fiedler, Tomas; Riani, Catur; Koczan, Dirk; Standar, Kerstin; Kreikemeyer, Bernd; Podbielski, Andreas

    2013-02-01

    Streptococcus pyogenes (group A streptococci [GAS]) encounter many streptococcal species of the physiological microbial biome when entering the upper respiratory tract of humans, leading to the question how GAS interact with these bacteria in order to establish themselves at this anatomic site and initiate infection. Here we show that S. oralis and S. salivarius in direct contact assays inhibit growth of GAS in a strain-specific manner and that S. salivarius, most likely via bacteriocin secretion, also exerts this effect in transwell experiments. Utilizing scanning electron microscopy documentation, we identified the tested strains as potent biofilm producers except for GAS M49. In mixed-species biofilms, S. salivarius dominated the GAS strains, while S. oralis acted as initial colonizer, building the bottom layer in mixed biofilms and thereby allowing even GAS M49 to form substantial biofilms on top. With the exception of S. oralis, artificial saliva reduced single-species biofilms and allowed GAS to dominate in mixed biofilms, although the overall two-layer structure was unchanged. When covered by S. oralis and S. salivarius biofilms, epithelial cells were protected from GAS adherence, internalization, and cytotoxic effects. Apparently, these species can have probiotic effects. The use of Affymetrix array technology to assess HEp-2 cell transcription levels revealed modest changes after exposure to S. oralis and S. salivarius biofilms which could explain some of the protective effects against GAS attack. In summary, our study revealed a protection effect of respiratory tract bacteria against an important airway pathogen and allowed a first in vitro insight into local environmental processes after GAS enter the respiratory tract. PMID:23241973

  8. Growth Phase-Dependent Modulation of Rgg Binding Specificity in Streptococcus pyogenes

    PubMed Central

    Anbalagan, Srivishnupriya; Dmitriev, Alexander; McShan, W. Michael; Dunman, Paul M.

    2012-01-01

    Streptococcus pyogenes Rgg is a transcriptional regulator that interacts with the cofactor LacD.1 to control growth phase-dependent expression of genes, including speB, which encodes a secreted cysteine protease. LacD.1 is thought to interact with Rgg when glycolytic intermediates are abundant in a manner that prevents Rgg-mediated activation of speB expression via binding to the promoter region. When the intermediates diminish, LacD.1 dissociates from Rgg and binds to the speB promoter to activate expression. The purpose of this study was to determine if Rgg bound to chromatin during the exponential phase of growth and, if so, to identify the binding sites. Rgg bound to 62 chromosomal sites, as determined by chromatin immunoprecipitation coupled with DNA microarrays. Thirty-eight were within noncoding DNA, including sites upstream of the genes encoding the M protein (M49), serum opacity factor (SOF), fibronectin-binding protein (SfbX49), and a prophage-encoded superantigen, SpeH. Each of these sites contained a promoter that was regulated by Rgg, as determined with transcriptional fusion assays. Purified Rgg also bound to the promoter regions of emm49, sof, and sfbX49 in vitro. Results obtained with a lacD.1 mutant showed that both LacD.1 and Rgg were necessary for the repression of emm49, sof, sfbX49, and speH expression. Overall, the results indicated that the DNA binding specificity of Rgg is responsive to environmental changes in a LacD.1-dependent manner and that Rgg and LacD.1 directly control virulence gene expression in the exponential phase of growth. PMID:22636768

  9. Streptococcus pyogenes Polymyxin B-Resistant Mutants Display Enhanced ExPortal Integrity

    PubMed Central

    Port, Gary C.; Vega, Luis A.; Nylander, Andrew B.

    2014-01-01

    The ExPortal protein secretion organelle in Streptococcus pyogenes is an anionic phospholipid-containing membrane microdomain enriched in Sec translocons and postsecretion protein biogenesis factors. Polymyxin B binds to and disrupts ExPortal integrity, resulting in defective secretion of several toxins. To gain insight into factors that influence ExPortal organization, a genetic screen was conducted to select for spontaneous polymyxin B-resistant mutants displaying enhanced ExPortal integrity. Whole-genome resequencing of 25 resistant mutants revealed from one to four mutations per mutant genome clustered primarily within a core set of 10 gene groups. Construction of mutants with individual deletions or insertions demonstrated that 7 core genes confer resistance and enhanced ExPortal integrity through loss of function, while 3 were likely due to gain of function and/or combinatorial effects. Core resistance genes include a transcriptional regulator of lipid biosynthesis, several genes involved in nutrient acquisition, and a variety of genes involved in stress responses. Two members of the latter class also function as novel regulators of the secreted SpeB cysteine protease. Analysis of the most frequently isolated mutation, a single nucleotide deletion in a track of 9 consecutive adenine residues in pstS, encoding a component of a high-affinity Pi transporter, suggests that this sequence functions as a molecular switch to facilitate stress adaptation. Together, these data suggest the existence of a membrane stress response that promotes enhanced ExPortal integrity and resistance to cationic antimicrobial peptides. PMID:24794568

  10. Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of emm89 Streptococcus pyogenes

    PubMed Central

    Zhu, Luchang; Olsen, Randall J.; Nasser, Waleed; de la Riva Morales, Ivan

    2015-01-01

    ABSTRACT Strains of emm89 Streptococcus pyogenes have become one of the major causes of invasive infections worldwide in the last 10years. We recently sequenced the genome of 1,125 emm89 strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3 nga promoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S.pyogenes NADase) and SLO (streptolysin O). Second, all clade 3 strains lack the hasABC locus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report that emm89 strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3 emm89 S.pyogenes. PMID:26443457

  11. Structure and Activity of Streptococcus pyogenes SipA: A Signal Peptidase-Like Protein Essential for Pilus Polymerisation

    PubMed Central

    Young, Paul G.; Proft, Thomas; Harris, Paul W. R.; Brimble, Margaret A.; Baker, Edward N.

    2014-01-01

    The pili expressed on the surface of the human pathogen Streptococcus pyogenes play an important role in host cell attachment, colonisation and pathogenesis. These pili are built from two or three components, an adhesin subunit at the tip, a major pilin that forms a polymeric shaft, and a basal pilin that is attached to the cell wall. Assembly is carried out by specific sortase (cysteine transpeptidase) enzyme. These components are encoded in a small gene cluster within the S. pyogenes genome, often together with another protein, SipA, whose function is unknown. We show through functional assays, carried out by expressing the S. pyogenes pilus components in Lactococcus lactis, SipA from the clinically important M1T1 strain is essential for pilus assembly, and that SipA function is likely to be conserved in all S. pyogenes. From the crystal structure of SipA we confirm that SipA belongs to the family of bacterial signal peptidases (SPases), which process the signal-peptides of secreted proteins. In contrast to a previous arm-swapped SipA dimer, this present structure shows that its principal domain closely resembles the catalytic domain of SPases and has a very similar peptide-binding cleft, but it lacks the catalytic Ser and Lys residues characteristic of SPases. In SipA these are replaced by Asp and Gly residues, which play no part in activity. We propose that SipA functions by binding a key component at the bacterial cell surface, in a conformation that facilitates pilus assembly. PMID:24911348

  12. Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding domain involved in adherence of streptococci to epithelial cells.

    PubMed Central

    Talay, S R; Valentin-Weigand, P; Jerlstrm, P G; Timmis, K N; Chhatwal, G S

    1992-01-01

    The sequence of the fibronectin-binding domain of the fibronectin-binding protein of Streptococcus pyogenes (Sfb protein) was determined, and its role in streptococcal adherence was investigated by use of an Sfb fusion protein in adherence studies. A 1-kb DNA fragment coding for the binding domain of Sfb protein was cloned into the expression vector pEX31 to produce an Sfb fusion protein consisting of the N-terminal part of MS2 polymerase and a C-terminal fragment of the streptococcal protein. Induction of the vector promoter resulted in hyperexpression of fibronectin-binding fusion protein in the cytoplasm of the recombinant Escherichia coli cells. Sequence determination of the cloned 1-kb fragment revealed an in-frame reading frame for a 268-amino-acid peptide composed of a 37-amino-acid sequence which is completely repeated three times and incompletely repeated a fourth time. Cloning of one repeat into pEX31 resulted in expression of small fusion peptides that show fibronectin-binding activity, indicating that one repeat contains at least one binding domain. Each repeat exhibits two charged domains and shows high homology with the 38-amino-acid D3 repeat of the fibronectin-binding protein of Staphylococcus aureus. Sequence comparison with other streptococcal ligand-binding surface proteins, including M protein, failed to reveal significant homology, which suggests that Sfb protein represents a novel type of functional protein in S. pyogenes. The Sfb fusion protein isolated from the cytoplasm of recombinant cells was purified by fast protein liquid chromatography. It showed a strong competitive inhibition of fibronectin binding to S. pyogenes and of the adherence of bacteria to cultured epithelial cells. In contrast, purified streptococcal lipoteichoic acid showed only a weak inhibition of fibronectin binding and streptococcal adherence. These results demonstrate that Sfb protein is directly involved in the fibronectin-mediated adherence of S. pyogenes to epithelial cells. Images PMID:1386839

  13. Insidious manifestation of pyogenic liver abscess caused by Streptococcus intermedius and Micrococcus luteus: a case report.

    PubMed

    Ioannou, Antreas; Xenophontos, Eleni; Karatsi, Alexandra; Petrides, Christos; Kleridou, Maro; Zintilis, Chrysostomos

    2016-01-01

    Pyogenic liver abscesses are caused by various microorganisms and usually present with fever, abdominal pain, leukocytosis and liver enzyme abnormalities. This case presents the insidious manifestation of a pyogenic liver abscess in a 34-year-old immunocompetent male, where classical manifestations of a liver abscess were absent. The microorganisms cultured from the abscess belonged to oral cavity's and gastrointestinal tract's normal flora. PMID:26770811

  14. Insidious manifestation of pyogenic liver abscess caused by Streptococcus intermedius and Micrococcus luteus: a case report

    PubMed Central

    Ioannou, Antreas; Xenophontos, Eleni; Karatsi, Alexandra; Petrides, Christos; Kleridou, Maro; Zintilis, Chrysostomos

    2016-01-01

    Pyogenic liver abscesses are caused by various microorganisms and usually present with fever, abdominal pain, leukocytosis and liver enzyme abnormalities. This case presents the insidious manifestation of a pyogenic liver abscess in a 34-year-old immunocompetent male, where classical manifestations of a liver abscess were absent. The microorganisms cultured from the abscess belonged to oral cavity's and gastrointestinal tract's normal flora. PMID:26770811

  15. In Vivo Expression of Streptococcus pyogenes Immunogenic Proteins during Tibial Foreign Body Infection

    PubMed Central

    Freiberg, Jeffrey A.; McIver, Kevin S.

    2014-01-01

    Group A streptococcus (GAS) is an important human pathogen that causes a number of diseases with a wide range of severities. While all known strains of GAS are still sensitive to penicillin, there have been reports of antibiotic treatment failure in as many as 20% to 40% of cases. Biofilm formation has been implicated as a possible cause for these failures. A biofilm is a microbially derived, sessile community where cells grow attached to a surface or as a bacterial conglomerate and surrounded by a complex extracellular matrix. While the ability of group A streptococcus to form biofilms in the laboratory has been shown, there is a lack of understanding of the role of GAS biofilms during an infection. We hypothesized that during infections, GAS exhibits a biofilm phenotype, complete with unique protein expression. To test this hypothesis, a rabbit model of GAS osteomyelitis was developed. A rabbit was inoculated with GAS using an infected indwelling device. Following the infection, blood and tissue samples were collected. Histological samples of the infected tibia were prepared, and the formation of a biofilm in vivo was visualized using peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) and confocal microscopy. In addition, Western blotting with convalescent rabbit serum detected cell wall proteins expressed in vitro under biofilm and planktonic growth conditions. Immunogenic proteins were then identified using matrix-assisted laser desorption ionization–time of flight tandem mass spectrometry (MALDI-TOF/TOF MS). These identities, along with the in vivo results, support the hypothesis that GAS forms biofilms during an infection. This unique phenotype should be taken into consideration when designing a vaccine or any other treatment for group A streptococcus infections. PMID:25001603

  16. M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island

    PubMed Central

    Panchaud, Alexandre; Guy, Lionel; Collyn, Franois; Haenni, Marisa; Nakata, Masanobu; Podbielski, Andreas; Moreillon, Philippe; Roten, Claude-Alain H

    2009-01-01

    Background The increasing number of completely sequenced bacterial genomes allows comparing their architecture and genetic makeup. Such new information highlights the crucial role of lateral genetic exchanges in bacterial evolution and speciation. Results Here we analyzed the twelve sequenced genomes of Streptococcus pyogenes by a nave approach that examines the preferential nucleotide usage along the chromosome, namely the usage of G versus C (GC-skew) and T versus A (TA-skew). The cumulative GC-skew plot presented an inverted V-shape composed of two symmetrical linear segments, where the minimum and maximum corresponded to the origin and terminus of DNA replication. In contrast, the cumulative TA-skew presented a V-shape, which segments were interrupted by several steep slopes regions (SSRs), indicative of a different nucleotide composition bias. Each S. pyogenes genome contained up to nine individual SSRs, encompassing all described strain-specific prophages. In addition, each genome contained a similar unique non-phage SSR, the core of which consisted of 31 highly homologous genes. This core includes the M-protein, other mga-related factors and other virulence genes, totaling ten intrinsic virulence genes. In addition to a high content in virulence-related genes and to a peculiar nucleotide bias, this SSR, which is 47 kb-long in a M1GAS strain, harbors direct repeats and a tRNA gene, suggesting a mobile element. Moreover, its complete absence in a M-protein negative group A Streptococcus natural isolate demonstrates that it could be spontaneously lost, but in vitro deletion experiments indicates that its excision occurred at very low rate. The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition. Conclusion Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation. Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants. PMID:19397826

  17. Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

    PubMed Central

    Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor

    2014-01-01

    SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436

  18. Disease manifestations and pathogenic mechanisms of group a Streptococcus.

    PubMed

    Walker, Mark J; Barnett, Timothy C; McArthur, Jason D; Cole, Jason N; Gillen, Christine M; Henningham, Anna; Sriprakash, K S; Sanderson-Smith, Martina L; Nizet, Victor

    2014-04-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436

  19. The NADase-Negative Variant of the Streptococcus pyogenes Toxin NAD+ Glycohydrolase Induces JNK1-Mediated Programmed Cellular Necrosis

    PubMed Central

    Chandrasekaran, Sukantha

    2016-01-01

    ABSTRACT Virulence factors are often multifunctional and contribute to pathogenesis through synergistic mechanisms. For the human pathogen Streptococcus pyogenes, two factors that act synergistically are the S. pyogenes NAD+ glycohydrolase (SPN) and streptolysin O (SLO). Through distinct mechanisms, SLO forms pores in host cell membranes and translocates SPN into the host cell cytosol. Two natural variants of SPN exist, one that exhibits NADase activity and one that lacks this function, and both versions are translocated and act in concert with SLO to cause an accelerated death response in epithelial cells. While NADase+ SPN is known to trigger a metabolic form of necrosis through the depletion of NAD+, the mechanism by which NADase− SPN induces cell death was unknown. In the studies described here, we examined the pathway of NADase− cell death through analysis of activation patterns of mitogen-activated protein kinases (MAPKs). S. pyogenes infection resulted in activation of members of three MAPK subfamilies (p38, ERK, and JNK). However, only JNK was activated in an SLO-specific manner. NADase− SPN induced necrosis in HeLa epithelial cells associated with depolarization of mitochondrial membranes, activation of NF-κB, and the generation of reactive oxygen species. Remarkably, RNA interference (RNAi) silencing of JNK protected cells from NADase−-SPN-mediated necrosis, suggesting that NADase− SPN triggers a form of programmed necrosis dependent on JNK signaling. Taken together, these data demonstrate that SPN acts with SLO to elicit necrosis through two different mechanisms depending on its NADase activity, i.e., metabolic (NADase+) or programmed (NADase−), leading to distinct inflammatory profiles. PMID:26838722

  20. Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-? and IgG3 Responses Compared with Children.

    PubMed

    Mortensen, Rasmus; Nissen, Thomas Nrrelykke; Blauenfeldt, Thomas; Christensen, Jan P; Andersen, Peter; Dietrich, Jes

    2015-08-15

    Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted protein. The response primarily consisted of three subsets of Th1 T cells, in which the TNF-?(+) and IL-2(+)TNF-?(+) subsets were most frequent. Humoral immunity was dominated by IgG1 and IgG3, whereas the Th2-associated IgG4 isotype was only detected at very low amounts. IgG3 levels correlated significantly with IFN-?, but not with IL-5, IL-13, IL-17, or TNF-?. Interestingly, children showed a similar pattern of Ag-specific cytokine release, but displayed significantly lower levels of IgG3 and IFN-? compared with adults. Thus, human immune responses against S. pyogenes consist of a robust Th1 cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed. PMID:26163588

  1. Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children

    PubMed Central

    Mortensen, Rasmus; Nissen, Thomas Nørrelykke; Fredslund, Sine; Rosenkrands, Ida; Christensen, Jan Pravsgaard; Andersen, Peter; Dietrich, Jes

    2016-01-01

    No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group of antigens was further validated using a high-density peptide array technology that also identified the linear epitopes. Based on immunological recognition, four targets were selected and tested for protective capabilities in an experimental GAS infection model in mice. Shown for the first time, three of these targets (spy0469, spy1228 and spy1801) conferred significant protection whereas one (spy1643) did not. PMID:26911649

  2. Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children.

    PubMed

    Mortensen, Rasmus; Nissen, Thomas Nrrelykke; Fredslund, Sine; Rosenkrands, Ida; Christensen, Jan Pravsgaard; Andersen, Peter; Dietrich, Jes

    2016-01-01

    No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group of antigens was further validated using a high-density peptide array technology that also identified the linear epitopes. Based on immunological recognition, four targets were selected and tested for protective capabilities in an experimental GAS infection model in mice. Shown for the first time, three of these targets (spy0469, spy1228 and spy1801) conferred significant protection whereas one (spy1643) did not. PMID:26911649

  3. Crystallization and preliminary X-ray crystallographic analysis of the tRNA-specific adenosine deaminase from Streptococcus pyogenes

    SciTech Connect

    Ku, Min-Je; Lee, Won-Ho; Nam, Ki-hyun; Rhee, Kyeong-hee; Lee, Ki-Seog; Kim, Eunice EunKyung; Yu, Myung-Hee; Hwang, Kwang Yeon

    2005-04-01

    The tRNA-specific adenosine deaminase from the pathogenic bacteria S. pyogenes has been overexpressed and crystallized. The tRNA-specific adenosine deaminase from the pathogenic bacteria Streptococcus pyogenes (spTAD) has been overexpressed in Escherichia coli and crystallized in the presence of Zn{sup 2+} ion at 295 K using ammonium sulfate as a precipitant. Flash-cooled crystals of spTAD diffracted to 2.0 Å using 30%(v/v) glycerol as a cryoprotectant. X-ray diffraction data have been collected to 2.0 Å using synchrotron radiation. The crystal belongs to the tetragonal space group P4{sub 2}2{sub 1}2, with unit-cell parameters a = b = 81.042, c = 81.270 Å. The asymmetric unit contains one subunit of spTAD, with a corresponding crystal volume per protein weight (V{sub M}) of 3.3 Å{sup 3} Da{sup −1} and a solvent content of 62.7%.

  4. Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes.

    PubMed

    Vitali, Luca Agostino; Di Luca, Maria Chiara; Prenna, Manuela; Petrelli, Dezemona

    2016-01-01

    We investigated the correlation between the genetic variation within mef(A)-msr(D) determinants of efflux-mediated erythromycin resistance in Streptococcus pyogenes and the level of erythromycin resistance. Twenty-eight mef(A)-positive strains were selected according to erythromycin MIC (4-32?g/mL), and their mef(A)-msr(D) regions were sequenced. Strains were classified according to the bacteriophage carrying mef(A)-msr(D). A new ?m46.1 genetic variant was found in 8 strains out of 28 and named VP_00501.1. Degree of allelic variation was higher in mef(A) than in msr(D). Hotspots for recombination were mapped within the locus that could have shaped the apparent mosaic structure of the region. There was a general correlation between mef(A)-msr(D) sequence and erythromycin resistance level. However, lysogenic conversion of susceptible strains by mef(A)-msr(D)-carrying ?m46.1 indicated that key determinants may not all reside within the mef(A)-msr(D) locus and that horizontal gene transfer could contribute to changes in the level of antibiotic resistance in S. pyogenes. PMID:26429294

  5. Non-instrumental immunoassay based on coloured polyacrolein latex: application to group-specific polysaccharide of Streptococcus pyogenes.

    PubMed

    Pavlova, I S; Lukin, Y V; Avdeev, D N; Kulshin, V A

    1995-05-01

    Non-instrumental immunoassay methods based on immunofiltration and microtiter particle agglutination (MPA) techniques have been developed using coloured polyacrolein latex. These methods have been applied to the quantification of the group-specific polysaccharide, A-PS, of S.pyogenes (group A Streptococcus) and compared to the standard ELISA tests. The assay with the ability to detect the lowest concentration of antigen was MPA; as little as 0.05 ng A-PS/ml or 10(4) cells/ml could be detected in 1.5 h. In comparison to ELISA test the sensitivity of MPA was 10 times higher and the procedure of the assay was much more simple. The sensitivity of the immunofiltration assay using both enzyme and latex markers was shown to be the same (50 ng A-PS/ml) and the duration of the assay 3-5 min. No cross-reactions of latex conjugates with non A Streptococcus cell lysates have been observed. The developed methods are easy to perform and require neither sophisticated equipment nor specially trained personal. PMID:7629278

  6. Superoxide anions produced by Streptococcus pyogenes group A-stimulated keratinocytes are responsible for cellular necrosis and bacterial growth inhibition.

    PubMed

    Regnier, Elodie; Grange, Philippe A; Ollagnier, Guillaume; Crickx, Etienne; Elie, Laetitia; Chouzenoux, Sandrine; Weill, Bernard; Plainvert, Cline; Poyart, Claire; Batteux, Frdric; Dupin, Nicolas

    2016-02-01

    Gram-positive Streptococcus pyogenes (group A Streptococcus or GAS) is a major skin pathogen and interacts with keratinocytes in cutaneous tissues. GAS can cause diverse suppurative and inflammatory infections, such as cellulitis, a common acute bacterial dermo-hypodermitis with a high morbidity. Bacterial isolation yields from the lesions are low despite the strong local inflammation observed, raising numerous questions about the pathogenesis of the infection. Using an invitro model of GAS-infected keratinocytes, we show that the major ROS produced is the superoxide anion ([Formula: see text]), and that its production is time- and dose-dependent. Using specific modulators of ROS production, we show that [Formula: see text] is mainly synthesized by the cytoplasmic NADPH oxidase. Superoxide anion production leads to keratinocyte necrosis but incomplete inhibition of GAS growth, suggesting that GAS may be partially resistant to the oxidative burst. In conclusion, GAS-stimulated keratinocytes are able to develop an innate immune response based on the production of ROS. This local immune response limits GAS development and induces keratinocyte cell death, resulting in the skin lesions observed in patients with cellulitis. PMID:26621818

  7. Structural and functional analysis of RopB: a major virulence regulator in Streptococcus pyogenes.

    PubMed

    Makthal, Nishanth; Gavagan, Maire; Do, Hackwon; Olsen, Randall J; Musser, James M; Kumaraswami, Muthiah

    2016-03-01

    Group A Streptococcus (GAS) is an exclusive human pathogen that causes significant disease burden. Global regulator RopB of GAS controls the expression of several major virulence factors including secreted protease SpeB during high cell density. However, the molecular mechanism for RopB-dependent speB expression remains unclear. To understand the mechanism of transcription activation by RopB, we determined the crystal structure of the C-terminal domain of RopB. RopB-CTD has the TPR motif, a signature motif involved in protein-peptide interactions and shares significant structural homology with the quorum sensing RRNPP family regulators. Characterization of the high cell density-specific cell-free growth medium demonstrated the presence of a low molecular weight proteinaceous secreted factor that upregulates RopB-dependent speB expression. Together, these results suggest that RopB and its cognate peptide signals constitute an intercellular signalling machinery that controls the virulence gene expression in concert with population density. Structure-guided mutational analyses of RopB dimer interface demonstrated that single alanine substitutions at this critical interface significantly altered RopB-dependent speB expression and attenuated GAS virulence. Results presented here suggested that a properly aligned RopB dimer interface is important for GAS pathogenesis and highlighted the dimerization interactions as a plausible therapeutic target for the development of novel antimicrobials. PMID:26714274

  8. Complete Genome Sequence of emm28 Type Streptococcus pyogenes MEW123, a Streptomycin-Resistant Derivative of a Clinical Throat Isolate Suitable for Investigation of Pathogenesis

    PubMed Central

    Jacob, Kristin M.; Spilker, Theodore; LiPuma, John J.; Dawid, Suzanne R.

    2016-01-01

    We present here the complete genome sequence of Streptococcus pyogenes type emm28 strain MEW123, a streptomycin-resistant derivative of a pediatric throat isolate. The genome length is 1,878,699 bp, with 38.29% G+C% content. The genome sequence adds value to this virulent emm28 representative strain and will aid in the investigation of streptococcal pathogenesis. PMID:26988051

  9. Complete Genome Sequence of emm28 Type Streptococcus pyogenes MEW123, a Streptomycin-Resistant Derivative of a Clinical Throat Isolate Suitable for Investigation of Pathogenesis.

    PubMed

    Jacob, Kristin M; Spilker, Theodore; LiPuma, John J; Dawid, Suzanne R; Watson, Michael E

    2016-01-01

    We present here the complete genome sequence of Streptococcus pyogenes type emm28 strain MEW123, a streptomycin-resistant derivative of a pediatric throat isolate. The genome length is 1,878,699 bp, with 38.29% G+C% content. The genome sequence adds value to this virulent emm28 representative strain and will aid in the investigation of streptococcal pathogenesis. PMID:26988051

  10. Epidemiological and molecular characteristics of clinical isolates of Streptococcus pyogenes collected between 2005 and 2008 from Chinese children.

    PubMed

    Liang, Yunmei; Liu, Xiaorong; Chang, Hesheng; Ji, Lili; Huang, Guoying; Fu, Zhou; Zheng, Yuejie; Wang, Libo; Li, Chengrong; Shen, Ying; Yu, Sangjie; Yao, Kaihu; Ma, Lin; Shen, Xuzhuang; Yang, Yonghong

    2012-07-01

    The aim of this study was to explore the epidemiological and molecular characteristics of Streptococcus pyogenes in children from different cities in mainland China who were diagnosed with scarlet fever, impetigo and pharyngitis, as well as to detect asymptomatic carriers, between 2005 and 2008, and to compare the results with isolates from rural Chinese children with acute glomerulonephritis in 2005 and in the 1990s. Susceptibility tests to determine MICs and analysis of the presence of erythromycin-resistant genes (mefA, ermB and ermA) and emm gene typing were performed on 466 S. pyogenes isolates from Beijing, Shanghai, Chongqing and Shenzhen. Superantigen genes (speA and speC) were examined by performing PCR on isolates with the most prevalent emm genotype. All isolates were sensitive to penicillin, cefradine and ofloxacin. The highest rate of resistance was against clarithromycin (98.1?%), followed by erythromycin (97.6?%), azithromycin and clindamycin (both 97.2?%), and tetracycline (94.0?%). Among the 466 isolates, 421 (90.3?%) harboured the ermB gene, 145 (31.1?%) were speA-positive and 273 (58.6?%) were speC-positive. The speA gene was common in emm1.0 (88.8?%) and emm6.5 (83.3?%) genotypes. The speC gene was frequently observed in emm4.0 (90.0?%), emm12.0 (69.6?%), emm18.0 (66.7?%), emm22.0 (75.9?%) and emm80.0 (80.0?%) genotypes. The most prevalent emm genotypes in mainland China in recent years were emm1.0 and emm12.0. All isolates remained sensitive to ?-lactams and quinolone. PMID:22442290

  11. Antimicrobial Susceptibility of Invasive Streptococcus pyogenes Isolates in Germany during 2003-2013

    PubMed Central

    Imöhl, Matthias; van der Linden, Mark

    2015-01-01

    A nationwide laboratory-based surveillance study of invasive S. pyogenes infections was conducted in Germany. Invasive isolates (n = 1,281) were obtained between 2003 and 2013. All isolates were susceptible to penicillin, cefotaxime and vancomycin. Tetracycline showed the highest rate of resistant or intermediate resistant isolates with 9.8%, followed by macrolides (4.0%), trimethoprim/sulfamethoxazole (SXT) (1.9%), levofloxacin (1.3%), chloramphenicol (0.9%) and clindamycin (0.7%). The most prominent trends were the appearance of levofloxacin non-susceptible isolates since 2011, and an increase of SXT non-susceptibility since 2012. PMID:26340445

  12. [Fc-receptor proteins of Streptococcus pyogenes and pathogenesis of post-infection complications].

    PubMed

    Totolian, A A; Burova, L A

    2014-01-01

    Phenomenon and mechanism of non-immune binding of immunoglobulins G and A by various emm-genotypes of group A streptococcus and in particular M-family proteins--main factors of pathogenicity of this causative agent of widespread human diseases are examined. The role of these receptor proteins in pathogenesis of post-streptococcal damage of kidneys (glomerules) and heart (myocarditis) are proved. Results of long-term studies that confirm hypothesis of initiating function of Fc-receptor M proteins in genesis of immune inflammation in organ tissues that precede development of glomerulonephritis and myocarditis are provided. According to the basic position, Fc-binding of an immunoglobulin by M proteins initiates production of anti-IgG, immune complexes of various composition and complement activation, deposition of those in tissues results in lymphocyte infiltration and production of pro-inflammatory cytokines. Literature data on the role of Fc-binding proteins in genesis of IgA-nephropathies and rheumatoid factor is also examined. An important role of other factors of the microbe is discussed such as cross-reacting antigens, erythrogenic toxin B, system of streptokinase-plasmin receptor or endostreptosin in post-streptococcal processes in kidneys. Their participation in the process must be mediated by an inflammation reaction in the tissue that is initiated by interaction of immunoglobulins with Fc-binding proteins of the microbe. A novel approach to understanding the nature of this pathology allowed to establish the ability of Fc-fragments of immunoglobulin G to suppress the development of the process. PMID:25286515

  13. RscA, a member of the MDR1 family of transporters, is repressed by CovR and required for growth of Streptococcus pyogenes under heat stress.

    PubMed

    Dalton, Tracy L; Collins, Julie T; Barnett, Timothy C; Scott, June R

    2006-01-01

    The ability of Streptococcus pyogenes (group A streptococcus [GAS]) to respond to changes in environmental conditions is essential for this gram-positive organism to successfully cause disease in its human host. The two-component system CovRS controls expression of about 15% of the GAS genome either directly or indirectly. In most operons studied, CovR acts as a repressor. We previously linked CovRS to the GAS stress response by showing that the sensor kinase CovS is required to inactivate the response regulator CovR so that GAS can grow under conditions of heat, acid, and salt stress. Here, we sought to identify CovR-repressed genes that are required for growth under stress. To do this, global transcription profiles were analyzed by microarrays following exposure to increased temperature (40 degrees C) and decreased pH (pH 6.0). The CovR regulon in an M type 6 strain of GAS was also examined by global transcriptional analysis. We identified a gene, rscA (regulated by stress and Cov), whose transcription was confirmed to be repressed by CovR and activated by heat and acid. RscA is a member of the MDR1 family of ABC transporters, and we found that it is required for growth of GAS at 40 degrees C but not at pH 6.0. Thus, for GAS to grow at 40 degrees C, CovR repression must be alleviated so that rscA can be transcribed to allow the production of this potential exporter. Possible explanations for the thermoprotective role of RscA in this pathogen are discussed. PMID:16352823

  14. A Highly Active and Negatively Charged Streptococcus pyogenes Lysin with a Rare d-Alanyl-l-Alanine Endopeptidase Activity Protects Mice against Streptococcal Bacteremia

    PubMed Central

    Lood, Rolf; Raz, Assaf; Molina, Henrik; Euler, Chad W.

    2014-01-01

    Bacteriophage endolysins have shown great efficacy in killing Gram-positive bacteria. PlyC, a group C streptococcal phage lysin, represents the most efficient lysin characterized to date, with a remarkably high specificity against different streptococcal species, including the important pathogen Streptococcus pyogenes. However, PlyC is a unique lysin, in terms of both its high activity and structure (two distinct subunits). We sought to discover and characterize a phage lysin active against S. pyogenes with an endolysin architecture distinct from that of PlyC to determine if it relies on the same mechanism of action as PlyC. In this study, we identified and characterized an endolysin, termed PlyPy (phage lysin from S. pyogenes), from a prophage infecting S. pyogenes. By in silico analysis, PlyPy was found to have a molecular mass of 27.8 kDa and a pI of 4.16. It was active against a majority of group A streptococci and displayed high levels of activity as well as binding specificity against group B and C streptococci, while it was less efficient against other streptococcal species. PlyPy showed the highest activity at neutral pH in the presence of calcium and NaCl. Surprisingly, its activity was not affected by the presence of the group A-specific carbohydrate, while the activity of PlyC was partly inhibited. Additionally, PlyPy was active in vivo and could rescue mice from systemic bacteremia. Finally, we developed a novel method to determine the peptidoglycan bond cleaved by lysins and concluded that PlyPy exhibits a rare d-alanyl-l-alanine endopeptidase activity. PlyPy thus represents the first lysin characterized from Streptococcus pyogenes and has a mechanism of action distinct from that of PlyC. PMID:24637688

  15. M-Protein Analysis of Streptococcus pyogenes Isolates Associated with Acute Rheumatic Fever in New Zealand.

    PubMed

    Williamson, Deborah A; Smeesters, Pierre R; Steer, Andrew C; Steemson, John D; Ng, Adrian C H; Proft, Thomas; Fraser, John D; Baker, Michael G; Morgan, Julie; Carter, Philip E; Moreland, Nicole J

    2015-11-01

    We applied an emm cluster typing system to group A Streptococcus strains in New Zealand, including those associated with acute rheumatic fever (ARF). We observed few so-called rheumatogenic emm types but found a high proportion of emm types previously associated with pyoderma, further suggesting a role for skin infection in ARF. PMID:26292296

  16. Case report: Co-infection of Rickettsia rickettsii and Streptococcus pyogenes: is fatal Rocky Mountain spotted fever underdiagnosed?

    PubMed

    Raczniak, Gregory A; Kato, Cecilia; Chung, Ida H; Austin, Amy; McQuiston, Jennifer H; Weis, Erica; Levy, Craig; Carvalho, Maria da Gloria S; Mitchell, Audrey; Bjork, Adam; Regan, Joanna J

    2014-12-01

    Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections. PMID:25331804

  17. Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology.

    PubMed

    Raz, Assaf; Tanasescu, Ana-Maria; Zhao, Anna M; Serrano, Anna; Alston, Tricia; Sol, Asaf; Bachrach, Gilad; Fischetti, Vincent A

    2015-01-01

    Cell wall anchored virulence factors are critical for infection and colonization of the host by Gram-positive bacteria. Such proteins have an N-terminal leader sequence and a C-terminal sorting signal, composed of an LPXTG motif, a hydrophobic stretch, and a few positively charged amino acids. The sorting signal halts translocation across the membrane, allowing sortase to cleave the LPXTG motif, leading to surface anchoring. Deletion of sortase prevents the anchoring of virulence factors to the wall; the effects on bacterial physiology however, have not been thoroughly characterized. Here we show that deletion of Streptococcus pyogenes sortase A leads to accumulation of sorting intermediates, particularly at the septum, altering cellular morphology and physiology, and compromising membrane integrity. Such cells are highly sensitive to cathelicidin, and are rapidly killed in blood and plasma. These phenomena are not a loss-of-function effect caused by the absence of anchored surface proteins, but specifically result from the accumulation of sorting intermediates. Reduction in the level of sorting intermediates leads to a return of the sortase mutant to normal morphology, while expression of M protein with an altered LPXTG motif in wild type cells leads to toxicity in the host environment, similar to that observed in the sortase mutant. These unanticipated effects suggest that inhibition of sortase by small-molecule inhibitors could similarly lead to the rapid elimination of pathogens from an infected host, making such inhibitors much better anti-bacterial agents than previously believed. PMID:26484774

  18. Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance.

    PubMed

    Davies, Mark R; Holden, Matthew T; Coupland, Paul; Chen, Jonathan H K; Venturini, Carola; Barnett, Timothy C; Zakour, Nouri L Ben; Tse, Herman; Dougan, Gordon; Yuen, Kwok-Yung; Walker, Mark J

    2015-01-01

    A scarlet fever outbreak began in mainland China and Hong Kong in 2011 (refs. 1-6). Macrolide- and tetracycline-resistant Streptococcus pyogenes emm12 isolates represent the majority of clinical cases. Recently, we identified two mobile genetic elements that were closely associated with emm12 outbreak isolates: the integrative and conjugative element ICE-emm12, encoding genes for tetracycline and macrolide resistance, and prophage ?HKU.vir, encoding the superantigens SSA and SpeC, as well as the DNase Spd1 (ref. 4). Here we sequenced the genomes of 141 emm12 isolates, including 132 isolated in Hong Kong between 2005 and 2011. We found that the introduction of several ICE-emm12 variants, ?HKU.vir and a new prophage, ?HKU.ssa, occurred in three distinct emm12 lineages late in the twentieth century. Acquisition of ssa and transposable elements encoding multidrug resistance genes triggered the expansion of scarlet fever-associated emm12 lineages in Hong Kong. The occurrence of multidrug-resistant ssa-harboring scarlet fever strains should prompt heightened surveillance within China and abroad for the dissemination of these mobile genetic elements. PMID:25401300

  19. TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes.

    PubMed

    Eigenbrod, Tatjana; Pelka, Karin; Latz, Eicke; Kreikemeyer, Bernd; Dalpke, Alexander H

    2015-08-01

    Microbial nucleic acids constitute an important group of pathogen-associated molecular patterns (PAMPs) that efficiently trigger innate immune activation. In mice, TLR13 has recently been identified to sense a highly conserved region within bacterial 23S rRNA. However, TLR13 is not expressed in humans, and the identity of its human homolog remains elusive. Moreover, the contribution of bacterial RNA to the induction of innate immune responses against entire bacteria is still insufficiently defined. In the current study, we show that human monocytes respond to bacterial RNA with secretion of IL-6, TNF, and IFN-β, which is critically dependent on lysosomal maturation. Using small interfering RNA and overexpression, we unambiguously identify TLR8 as receptor for bacterial RNA in primary human monocyte-derived macrophages. We further demonstrate that the sequence motif sensed by TLR8 is clearly distinct from that recognized by TLR13. Moreover, TLR8-dependent detection of bacterial RNA was critical for triggering monocyte activation in response to infection with Streptococcus pyogenes. Bacterial RNA within streptococci was also a dominant stimulus for murine immune cells, highlighting the physiological relevance of RNA sensing in defense of infections. PMID:26101323

  20. Streptococcus pyogenes Sortase Mutants Are Highly Susceptible to Killing by Host Factors Due to Aberrant Envelope Physiology

    PubMed Central

    Raz, Assaf; Tanasescu, Ana-Maria; Zhao, Anna M.; Serrano, Anna; Alston, Tricia; Sol, Asaf; Bachrach, Gilad; Fischetti, Vincent A.

    2015-01-01

    Cell wall anchored virulence factors are critical for infection and colonization of the host by Gram-positive bacteria. Such proteins have an N-terminal leader sequence and a C-terminal sorting signal, composed of an LPXTG motif, a hydrophobic stretch, and a few positively charged amino acids. The sorting signal halts translocation across the membrane, allowing sortase to cleave the LPXTG motif, leading to surface anchoring. Deletion of sortase prevents the anchoring of virulence factors to the wall; the effects on bacterial physiology however, have not been thoroughly characterized. Here we show that deletion of Streptococcus pyogenes sortase A leads to accumulation of sorting intermediates, particularly at the septum, altering cellular morphology and physiology, and compromising membrane integrity. Such cells are highly sensitive to cathelicidin, and are rapidly killed in blood and plasma. These phenomena are not a loss-of-function effect caused by the absence of anchored surface proteins, but specifically result from the accumulation of sorting intermediates. Reduction in the level of sorting intermediates leads to a return of the sortase mutant to normal morphology, while expression of M protein with an altered LPXTG motif in wild type cells leads to toxicity in the host environment, similar to that observed in the sortase mutant. These unanticipated effects suggest that inhibition of sortase by small-molecule inhibitors could similarly lead to the rapid elimination of pathogens from an infected host, making such inhibitors much better anti-bacterial agents than previously believed. PMID:26484774

  1. Inactivation of Streptococcus pyogenes extracellular cysteine protease significantly decreases mouse lethality of serotype M3 and M49 strains.

    PubMed Central

    Lukomski, S; Sreevatsan, S; Amberg, C; Reichardt, W; Woischnik, M; Podbielski, A; Musser, J M

    1997-01-01

    Cysteine proteases have been implicated as important virulence factors in a wide range of prokaryotic and eukaryotic pathogens, but little direct evidence has been presented to support this notion. Virtually all strains of the human bacterial pathogen Streptococcus pyogenes express a highly conserved extracellular cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB). Two sets of isogenic strains deficient in SpeB cysteine protease activity were constructed by integrational mutagenesis using nonreplicating recombinant plasmids containing a truncated segment of the speB gene. Immunoblot analyses and enzyme assays confirmed that the mutant derivatives were deficient in expression of enzymatically active SpeB cysteine protease. To test the hypothesis that the cysteine protease participates in host mortality, we assessed the ability of serotype M3 and M49 wild-type strains and isogenic protease-negative mutants to cause death in outbred mice after intraperitoneal inoculation. Compared to wild-type parental organisms, the serotype M3 speB mutant lost virtually all ability to cause mouse death (P < 0.00001), and similarly, the virulence of the M49 mutant was detrimentally altered (P < 0.005). The data unambiguously demonstrate that the streptococcal enzyme is a virulence factor, and thereby provide additional evidence that microbial cysteine proteases are critical in host-pathogen interactions. PMID:9169486

  2. Potential antibiotic and anti-infective effects of rhodomyrtone from Rhodomyrtus tomentosa (Aiton) Hassk. on Streptococcus pyogenes as revealed by proteomics.

    PubMed

    Limsuwan, Surasak; Hesseling-Meinders, Anne; Voravuthikunchai, Supayang Piyawan; van Dijl, Jan Maarten; Kayser, Oliver

    2011-08-15

    Rhodomyrtone from Rhodomyrtus tomentosa (Aiton) Hassk. leaf extract has a strong antibacterial activity against the bacterial pathogen Streptococcus pyogenes. Our previous studies indicated that the bactericidal activity of rhodomyrtone might involve intracellular targets. In the present studies we followed a proteomics approach to investigate the mode of action of rhodomyrtone on S. pyogenes. For this purpose, S. pyogenes was cultivated in the presence of 0.39 ?g/ml rhodomyrtone, which corresponds to 50% of the minimal inhibitory concentration. The results show that the amounts of various enzymes associated with important metabolic pathways were strongly affected, which is consistent with the growth-inhibiting effect of rhodomyrtone. Additionally, cells of S. pyogenes grown in the presence of rhodomyrtone produced reduced amounts of known virulence factors, such as the glyceraldehyde-3-phosphate dehydrogenase, the CAMP factor, and the streptococcal pyrogenic exotoxin C. Taken together, these findings indicate that rhodomyrtone has both antimicrobial and anti-infective activities, which make it an interesting candidate drug. PMID:21439802

  3. [Carriage of Streptococcus pyogenes in primary school children: M-protein types, pyrogenic toxin genes, and investigation of the clonal relationships between the isolates].

    PubMed

    Otlu, Bar??; Karakurt, Cem?it; Bay?nd?r, Ya?ar; Kayaba?, ner; Yakupo?ullar?, Yusuf; Gzkara Ba?, Harika

    2015-07-01

    M-protein and pyrogenic toxins are the most important virulence factors of Streptococcus pyogenes, and they play significant role in the pathophysiology of acute rheumatoid fever and scarlet fever, respectively. In this study, the pharyngeal carriage of S.pyogenes of the primary school children, clonal relationship of the strains, M-protein types, and the presence of pyrogenic toxin genes were aimed to be investigated. A total of 668 throat cultures obtained from children (age range: 6-16 years) in two primary schools in our region, were included in the study. The clonal relationships of the isolated group A streptococci (GAS) strains were investigated by DiversiLab assay (BioMrieux, France), and the clonal relatedness was confirmed by pulsed-field gel electrophoresis (PFGE) method. M-protein (emm) typing was performed by DNA sequencing as suggested by Centers for Disease Control and Prevention (CDC). The genes encoding pyrogenic toxins, speA and speC, were investigated by an in-house multiplex polymerase chain reaction (PCR) method. S.pyogenes was isolated from 134 (20.05%) of the throat samples. The GAS carriage rate of the students aged ?10 was statistically higher than those 7-9 years age group (%22 vs %16.4, p<0.05). The M protein gene could be characterized only among 123 isolates by DNA sequencing, and 20 different emm types were detected. The most frequent emm type was emm1 (n=38, 30.9%) followed by emm12 (n=18, 14.6%), emm89 (n=10, 8.1%), emm118 (n=9, 7.3%), and emm4 (n=7, 5.7%). Pyrogenic toxin genes were found in 25 (18.6%) of the isolates, including speA in 11 isolates (8.2%) and speC in 12 isolates (8.9%) and both genes were detected in 2 isolates (1.5%). Sixty-two different Rep (Repetitive extragenic palindromic)-PCR profiles were detected in 134 S.pyogenes isolates by DiversiLab method. Thirteen different clusters were formed by a total of clonally related 36 isolates revealing a strain clustering ratio of 26.9%. Clonal relationship of all isolates in the same cluster was confirmed by PFGE method. In this study, relatively high percentage of GAS carriage was observed among primary school children in our region. The coverage rate of the 30-valent vaccine was determined to be over 90% with respect to M-protein types. Since the pyrogenic toxin-encoding genes were found in one fifth of the isolates from the studied subjects, we concluded that the carrier population may also have high risk for scarlet fever. We also concluded that, the clonal relationship ratio determined among the isolates may be a risk in school transmission of GAS. PMID:26313273

  4. Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation

    PubMed Central

    Maddocks, Sarah E; Wright, Christopher J; Nobbs, Angela H; Brittan, Jane L; Franklin, Linda; Strömberg, Nicklas; Kadioglu, Aras; Jepson, Mark A; Jenkinson, Howard F

    2011-01-01

    The streptococcal antigen I/II (AgI/II)-family polypeptides are cell wall-anchored adhesins expressed by most indigenous oral streptococci. Proteins sharing 30–40% overall amino acid sequence similarities with AgI/II-family proteins are also expressed by Streptococcus pyogenes. The S. pyogenes M28_Spy1325 polypeptide (designated AspA) displays an AgI/II primary structure, with alanine-rich (A) and proline-rich (P) repeats flanking a V region that is projected distal from the cell. In this study it is shown that AspA from serotype M28 S. pyogenes, when expressed on surrogate host Lactococcus lactis, confers binding to immobilized salivary agglutinin gp-340. This binding was blocked by antibodies to the AspA-VP region. In contrast, the N-terminal region of AspA was deficient in binding fluid-phase gp-340, and L. lactis cells expressing AspA were not agglutinated by gp-340. Deletion of the aspA gene from two different M28 strains of S. pyogenes abrogated their abilities to form biofilms on saliva-coated surfaces. In each mutant strain, biofilm formation was restored by trans complementation of the aspA deletion. In addition, expression of AspA protein on the surface of L. lactis conferred biofilm-forming ability. Taken collectively, the results provide evidence that AspA is a biofilm-associated adhesin that may function in host colonization by S. pyogenes. PMID:21736640

  5. Increased kasugamycin sensitivity in Escherichia coli caused by the presence of an inducible erythromycin resistance (erm) gene of Streptococcus pyogenes.

    PubMed

    Suvorov, A N; van Gemen, B; van Knippenberg, P H

    1988-12-01

    An inducible erythromycin resistance gene (erm) of Streptococcus pyogenes was introduced into Escherichia coli by transformation with a plasmid. The recipient E. coli cells were either kasugamycin sensitive (wildtype) or kasugamycin resistant (ksgA). The MIC values of erythromycin increased from 150 micrograms/ml to greater than 3000 micrograms/ml for E. coli. An extract of transformed cells, particularly a high-salt ribosomal wash, contained an enzyme that was able to methylate 23S rRNA from untransformed cells in vitro; however, 23S rRNA from transformed cells was not a substrate for methylation by such an extract. 165 rRNA and 30S ribosomal subunits of either the wild type or a kasugamycin resistant (ksgA) mutant were not methylated in vitro. Transformation of E. coli by the erm-containing plasmid led to a reduction of the MIC values for kasugamycin. This happened in wild-type as well as in ksgA cells. However, in vitro experiments with purified ksgA encoded methylase demonstrated that also in erm transformed E. coli, the ksgA encoded enzyme was active in wild-type, but not in ksgA cells. It was also shown by in vitro experiments that ribosomes from erm ksgA cells have become sensitive to kasugamycin. Our experiments show that in vivo methylation of 23S rRNA, presumably of the adenosine at position 2058, leads to enhanced resistance to erythromycin and to reduced resistance to kasugamycin. This, together with previous data, argues for a close proximity of the two sites on the ribosome that are substrates for adenosine dimethylation. PMID:3071738

  6. Structural Analysis of Streptococcus pyogenes NADH Oxidase: Conformational Dynamics Involved in Formation of the C(4a)-Peroxyflavin Intermediate.

    PubMed

    Wallen, Jamie R; Mallett, T Conn; Okuno, Takashi; Parsonage, Derek; Sakai, Hiroaki; Tsukihara, Tomitake; Claiborne, Al

    2015-11-17

    In probing the oxygen reactivity of an Enterococcus faecalis NADH oxidase (Nox; O2 ? 2H2O) C42S mutant lacking the Cys42-sulfenic acid (Cys42-SOH) redox center, we provided direct evidence of a C(4a)-peroxyflavin intermediate in the oxidative half-reaction and also described a conformational or chemical change that is rate-limiting for full reoxidation of the homodimer. In this work, the Nox from Streptococcus pyogenes (SpyNox) has been expressed and crystallized, and the overoxidized wild-type [Cys44-SOH ? Cys44-sulfinic acid (Cys44-SO2H)] and C44S mutant enzyme structures have been refined at 2.0 and 2.15 , respectively. We show that azide binds to the two-electron reduced wild-type (EH2) enzyme and to the mutant enzyme in solution, but with a significantly higher affinity for the mutant protein. The spectral course of the titration with the SpyNox EH2 form clearly indicates progressive displacement of the Cys44-S(-) ? FAD charge-transfer interaction. An azide soak with C44S Nox crystals led to the structure of the complex, as refined at 2.10 . The active-site N3(-) ligand is proximal to the Ser44 and His11 side chains, and a significant shift in the Ser44 side chain also appears. This provides an attractive explanation for the azide-induced loss of charge-transfer absorbance seen with the wild-type EH2 form and also permits accommodation of a C(4a)-peroxyflavin structural model. The conformation of Ser44 and the associated helical element, and the resulting steric accommodation, appear to be linked to the conformational change described in the E. faecalis C42S Nox oxidative half-reaction. PMID:26506002

  7. Streptococcus pyogenes type M12 protein shows selective binding to some human immunoglobulin G3 myeloma proteins.

    PubMed Central

    Johansson, P J; Malone, C C; Williams, R C; Retnoningrum, D S; Cleary, P P

    1994-01-01

    Purified, recombinant M12 protein from Streptococcus pyogenes CS24 has recently been demonstrated to bind human immunoglobulin G3 (IgG3). The binding site for IgG has been localized to an internal peptide encoded by a PvuII fragment of the gene emm12. We have investigated the ability of an isolated recombinant M12 protein consisting of the peptide encoded by the PvuII fragment to bind various monoclonal human IgG3 myeloma proteins representing a number of both Caucasian and Oriental IgG3 Gm(allotypic) phenotypes. Of nine Caucasian IgG3 myeloma proteins, only two bound strongly to the recombinant M12 protein in enzyme-linked immunosorbent assays. The allotypic phenotypes of the reactive proteins were IgG3m(b+)(g-) and IgG3m(b-)(g+). No binding was seen for seven IgG3 myeloma proteins of Oriental origin with G3m(st+)(u-)(b+)(g-), G3m(st-)(u+)(b+)(g-), G3m(st-)(u+)(b-)(g+), and G3m(st-)(u-)(b-)(g+) phenotypes. The binding of human IgG3 to M12 protein seems to be related to features other than its Gm allotypic markers. Selective reactivity of IgG3 myeloma proteins with M12 protein may provide another way to subclassify human IgG3 molecules. The biological significance of the selective reactivity is not known. PMID:8039929

  8. Unique genomic arrangements in an invasive serotype M23 strain of Streptococcus pyogenes identify genes that induce hypervirulence.

    PubMed

    Bao, Yunjuan; Liang, Zhong; Booyjzsen, Claire; Mayfield, Jeffrey A; Li, Yang; Lee, Shaun W; Ploplis, Victoria A; Song, Hui; Castellino, Francis J

    2014-12-01

    The first genome sequence of a group A Streptococcus pyogenes serotype M23 (emm23) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF(-)) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ?M23ND.1 to ?M23ND.4, harboring genes encoding streptococcal superantigen (ssa), streptococcal pyrogenic exotoxins (speC, speH, and speI), and DNases (spd1 and spd3), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The covS sensor in M23ND was identified as a pseudogene, resulting in the attenuation of speB function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (mga), M protein (emm23), C5a peptidase (scpA), fibronectin-binding proteins (sfbI and fbp54), streptolysin O (slo), hyaluronic acid capsule (hasA), streptokinase (ska), and DNases (spd and spd3), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors. PMID:25225265

  9. Differences between Macrolide-Resistant and -Susceptible Streptococcus pyogenes: Importance of Clonal Properties in Addition to Antibiotic Consumption

    PubMed Central

    Silva-Costa, C.; Friães, A.; Melo-Cristino, J.

    2012-01-01

    A steady decline in macrolide resistance among Streptococcus pyogenes (group A streptococci [GAS]) in Portugal was reported during 1999 to 2006. This was accompanied by alterations in the prevalence of macrolide resistance phenotypes and in the clonal composition of the population. In order to test whether changes in the macrolide-resistant population reflected the same changing patterns of the overall population, we characterized both macrolide-susceptible and -resistant GAS associated with a diagnosis of tonsillo-pharyngitis recovered in the period from 2000 to 2005 in Portugal. Pulsed-field gel electrophoresis (PFGE) profiling was the best predictor of emm type and the only typing method that could discriminate clones associated with macrolide resistance and susceptibility within each emm type. Six PFGE clusters were significantly associated with macrolide susceptibility: T3-emm3-ST406, T4-emm4-ST39, T1-emm1-ST28, T6-emm6-ST382, B3264-emm89-ST101/ST408, and T2-emm2-ST55. Four PFGE clusters were associated with macrolide resistance: T4-emm4-ST39, T28-emm28-ST52, T12-emm22-ST46, and T1-emm1-ST28. We found no evidence for frequent ongoing horizontal transfer of macrolide resistance determinants. The diversity of the macrolide-resistant population was lower than that of susceptible isolates. The differences found between the two populations suggest that the macrolide-resistant population of GAS has its own dynamics, independent of the behavior of the susceptible population. PMID:22908153

  10. Differences between macrolide-resistant and -susceptible Streptococcus pyogenes: importance of clonal properties in addition to antibiotic consumption.

    PubMed

    Silva-Costa, C; Friães, A; Ramirez, M; Melo-Cristino, J

    2012-11-01

    A steady decline in macrolide resistance among Streptococcus pyogenes (group A streptococci [GAS]) in Portugal was reported during 1999 to 2006. This was accompanied by alterations in the prevalence of macrolide resistance phenotypes and in the clonal composition of the population. In order to test whether changes in the macrolide-resistant population reflected the same changing patterns of the overall population, we characterized both macrolide-susceptible and -resistant GAS associated with a diagnosis of tonsillo-pharyngitis recovered in the period from 2000 to 2005 in Portugal. Pulsed-field gel electrophoresis (PFGE) profiling was the best predictor of emm type and the only typing method that could discriminate clones associated with macrolide resistance and susceptibility within each emm type. Six PFGE clusters were significantly associated with macrolide susceptibility: T3-emm3-ST406, T4-emm4-ST39, T1-emm1-ST28, T6-emm6-ST382, B3264-emm89-ST101/ST408, and T2-emm2-ST55. Four PFGE clusters were associated with macrolide resistance: T4-emm4-ST39, T28-emm28-ST52, T12-emm22-ST46, and T1-emm1-ST28. We found no evidence for frequent ongoing horizontal transfer of macrolide resistance determinants. The diversity of the macrolide-resistant population was lower than that of susceptible isolates. The differences found between the two populations suggest that the macrolide-resistant population of GAS has its own dynamics, independent of the behavior of the susceptible population. PMID:22908153

  11. Pyrogenicity and Cytokine-Inducing Properties of Streptococcus pyogenes Superantigens: Comparative Study of Streptococcal Mitogenic Exotoxin Z and Pyrogenic Exotoxin A

    PubMed Central

    Müller-Alouf, Heide; Proft, Thomas; Zollner, Thomas M.; Gerlach, Dieter; Champagne, Eric; Desreumaux, Pierre; Fitting, Catherine; Geoffroy-Fauvet, Christiane; Alouf, Joseph E.; Cavaillon, Jean-Marc

    2001-01-01

    Streptococcal mitogenic exotoxin Z (SMEZ), a superantigen derived from Streptococcus pyogenes, provoked expansion of human lymphocytes expressing the Vβ 2, 4, 7 and 8 motifs of T-cell receptor. SMEZ was pyrogenic in rabbits and stimulated the expression of the T-cell activation markers CD69 and cutaneous lymphocyte-associated antigen. A variety of cytokines was released by human mononuclear leukocytes stimulated with SMEZ, which was 10-fold more active than streptococcal pyrogenic exotoxin A. Th2-derived cytokines were elicited only by superantigens and not by streptococcal cells. PMID:11349089

  12. Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes

    PubMed Central

    Gordon, Lily D.; Fang, Zhong; Holder, Robert C.; Reid, Sean D.

    2015-01-01

    ABSTRACT Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. IMPORTANCE Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. PMID:26013489

  13. Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays

    PubMed Central

    2012-01-01

    Background Small non-coding RNAs (sRNAs) have attracted attention as a new class of gene regulators in both eukaryotes and bacteria. Genome-wide screening methods have been successfully applied in Gram-negative bacteria to identify sRNA regulators. Many sRNAs are well characterized, including their target mRNAs and mode of action. In comparison, little is known about sRNAs in Gram-positive pathogens. In this study, we identified novel sRNAs in the exclusively human pathogen Streptococcus pyogenes M49 (Group A Streptococcus, GAS M49), employing a whole genome intergenic tiling array approach. GAS is an important pathogen that causes diseases ranging from mild superficial infections of the skin and mucous membranes of the naso-pharynx, to severe toxic and invasive diseases. Results We identified 55 putative sRNAs in GAS M49 that were expressed during growth. Of these, 42 were novel. Some of the newly-identified sRNAs belonged to one of the common non-coding RNA families described in the Rfam database. Comparison of the results of our screen with the outcome of two recently published bioinformatics tools showed a low level of overlap between putative sRNA genes. Previously, 40 potential sRNAs have been reported to be expressed in a GAS M1T1 serotype, as detected by a whole genome intergenic tiling array approach. Our screen detected 12 putative sRNA genes that were expressed in both strains. Twenty sRNA candidates appeared to be regulated in a medium-dependent fashion, while eight sRNA genes were regulated throughout growth in chemically defined medium. Expression of candidate genes was verified by reverse transcriptase-qPCR. For a subset of sRNAs, the transcriptional start was determined by 5′ rapid amplification of cDNA ends-PCR (RACE-PCR) analysis. Conclusions In accord with the results of previous studies, we found little overlap between different screening methods, which underlines the fact that a comprehensive analysis of sRNAs expressed by a given organism requires the complementary use of different methods and the investigation of several environmental conditions. Despite a high conservation of sRNA genes within streptococci, the expression of sRNAs appears to be strain specific. PMID:23062031

  14. Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with tonsil colonisation by Streptococcus pyogenes

    PubMed Central

    Viciani, Elisa; Montagnani, Francesca; Tavarini, Simona; Tordini, Giacinta; Maccari, Silvia; Morandi, Matteo; Faenzi, Elisa; Biagini, Cesare; Romano, Antonio; Salerni, Lorenzo; Finco, Oretta; Lazzi, Stefano; Ruggiero, Paolo; De Luca, Andrea; Barocchi, Michèle A.; Manetti, Andrea G. O.

    2016-01-01

    The involvement of pathogenic bacteria in obstructive sleep apnoea syndrome (OSAS) has yet to be elucidated. We investigated the possible role of group A streptococcus (GAS) in OSAS pathogenesis. In 40 tonsillectomized patients affected by OSAS and 80 healthy controls, significant (p < 0.0001) association of GAS with paediatric OSAS was found. Supernatant from streptolysin O (SLO)-producing GAS induced production of cysteinyl leukotrienes (CysLTs) in tonsil mononuclear cells (TMCs). CysLTs-treated TMCs showed significant (p < 0.05) proliferation of CD4+ T, CD19+ and CD19+CD27+CD38+ B lymphocytes. We discovered a SLO-dependent activation of CysLTs production through a pathway involving TOLL-like receptor 4 (TLR4), TIR-domain-containing adapter-inducing interferon-β (TRIF), Myeloid differentiation primary response gene 88 (MyD88), and p38 MAP Kinase. In conclusion, we hypothesise that GAS may contribute to paediatric tonsillar hyperplasia through CysLTs production induced by SLO, and this might explain its association with OSAS. PMID:26860261

  15. Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with tonsil colonisation by Streptococcus pyogenes.

    PubMed

    Viciani, Elisa; Montagnani, Francesca; Tavarini, Simona; Tordini, Giacinta; Maccari, Silvia; Morandi, Matteo; Faenzi, Elisa; Biagini, Cesare; Romano, Antonio; Salerni, Lorenzo; Finco, Oretta; Lazzi, Stefano; Ruggiero, Paolo; De Luca, Andrea; Barocchi, Michle A; Manetti, Andrea G O

    2016-01-01

    The involvement of pathogenic bacteria in obstructive sleep apnoea syndrome (OSAS) has yet to be elucidated. We investigated the possible role of group A streptococcus (GAS) in OSAS pathogenesis. In 40 tonsillectomized patients affected by OSAS and 80 healthy controls, significant (p?

  16. Myosin Cross-reactive Antigen of Streptococcus pyogenes M49 Encodes a Fatty Acid Double Bond Hydratase That Plays a Role in Oleic Acid Detoxification and Bacterial Virulence

    PubMed Central

    Volkov, Anton; Liavonchanka, Alena; Kamneva, Olga; Fiedler, Tomas; Goebel, Cornelia; Kreikemeyer, Bernd; Feussner, Ivo

    2010-01-01

    The myosin cross-reactive antigen (MCRA) protein family is highly conserved among different bacterial species ranging from Gram-positive to Gram-negative bacteria. Besides their ubiquitous occurrence, knowledge about the biochemical and physiological function of MCRA proteins is scarce. Here, we show that MCRA protein from Streptococcus pyogenes M49 is a FAD enzyme, which acts as hydratase on (9Z)- and (12Z)-double bonds of C-16, C-18 non-esterified fatty acids. Products are 10-hydroxy and 10,13-dihydroxy fatty acids. Kinetic analysis suggests that FAD rather stabilizes the active conformation of the enzyme and is not directly involved in catalysis. Analysis of S. pyogenes M49 grown in the presence of either oleic or linoleic acid showed that 10-hydroxy and 10,13-dihydroxy derivatives were the only products. No further metabolism of these hydroxy fatty acids was detected. Deletion of the hydratase gene caused a 2-fold decrease in minimum inhibitory concentration against oleic acid but increased survival of the mutant strain in whole blood. Adherence and internalization properties to human keratinocytes were reduced in comparison with the wild type. Based on these results, we conclude that the previously identified MCRA protein can be classified as a FAD-containing double bond hydratase, within the carbon-oxygen lyase family, that plays a role in virulence of at least S. pyogenes M49. PMID:20145247

  17. Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for Streptococcus pyogenes Virulence

    PubMed Central

    Jin, Hong; Agarwal, Shivangi; Agarwal, Shivani; Pancholi, Vijay

    2011-01-01

    ABSTRACT Streptococcal surface dehydrogenase (SDH) (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) is an anchorless major multifunctional surface protein in group A Streptococcus (GAS) with the ability to bind important mammalian proteins, including plasmin(ogen). Although several biological properties of SDH are suggestive of its possible role in GAS virulence, its direct role in GAS pathogenesis has not been ascertained because it is essential for GAS survival. Thus, it has remained enigmatic as to how and why SDH/GAPDH is exported onto the bacterial surface. The present investigation highlights why SDH is exported onto the GAS surface. Differential microarray-based genome-wide transcript abundance analysis was carried out using a specific mutant, which was created by inserting a hydrophobic tail at the C-terminal end of SDH (M1-SDHHBtail) and thus preventing its exportation onto the GAS surface. This analysis revealed downregulation of the majority of genes involved in GAS virulence and genes belonging to carbohydrate and amino acid metabolism and upregulation of those related to lipid metabolism. The complete attenuation of this mutant for virulence in the mouse model and the decreased and increased virulence of the wild-type and mutant strains postcomplementation with SDHHBtail and SDH, respectively, indicated that the SDH surface export indeed regulates GAS virulence. M1-SDHHBtail also displayed unaltered growth patterns, increased intracellular ATP concentration and Hpr double phosphorylation, and significantly reduced pH tolerance, streptolysin S, and SpeB activities. These phenotypic and physiological changes observed in the mutant despite the unaltered expression levels of established transcriptional regulators further highlight the fact that SDH interfaces with many regulators and its surface exportation is essential for GAS virulence. PMID:21628503

  18. Resistance to Erythromycin and Telithromycin in Streptococcus pyogenes Isolates Obtained between 1999 and 2002 from Greek Children with Tonsillopharyngitis: Phenotypic and Genotypic Analysis

    PubMed Central

    Grivea, Ioanna N.; Al-Lahham, Adnan; Katopodis, George D.; Syrogiannopoulos, George A.; Reinert, Ralf René

    2006-01-01

    Since the late 1990s, the prevalence of erythromycin-resistant Streptococcus pyogenes has significantly increased in several European countries. Between January 1999 and December 2002, 1,577 isolates of S. pyogenes were recovered from children with tonsillopharyngitis living in various areas of Western Greece. Erythromycin resistance was observed in 379 (24%) of the 1,577 isolates. All erythromycin-resistant strains along with 153 randomly selected erythromycin-susceptible S. pyogenes isolates were tested for their antimicrobial susceptibility, resistance phenotypes, and genotypes. Representative isolates underwent emm gene sequence typing. Isolates with reduced susceptibility to telithromycin (MIC, ≥2 μg/ml) were studied for multilocus sequence type, L22, L4, and 23S rRNA mutations. Of the total 379 erythromycin-resistant isolates, 193 (50.9%) harbored the mef(A) gene, 163 (43%) erm(A), 1 (0.3%) mef(A) plus erm(A), and 22 (5.8%) the erm(B) gene. Among the erythromycin-susceptible isolates, emm 1 (25%), emm 2 (12.5%), and emm 77 (12.5%) predominated. Furthermore, among the erythromycin-resistant isolates, emm 4 (30.6%), emm 28 (22.2%), and emm 77 (12.5%) prevailed. Resistance to telithromycin was observed in 22 (5.8%) of the erythromycin-resistant isolates. Sixteen (72.7%) of the 22 isolates appeared to be clonally related, since all of them belonged to emm type 28 and multilocus sequence type 52. One of the well-known mutations (T2166C) in 23S rRNA, as well as a new one (T2136C), was detected in erythromycin- and telithromycin-resistant isolates. High incidence of macrolide resistance and clonal spread of telithromycin resistance were the characteristics of the Greek S. pyogenes isolates obtained from 1999 to 2002. PMID:16377695

  19. Epidemiological Study of Erythromycin-Resistant Streptococcus pyogenes From Korea and Japan by emm Genotyping and Multilocus Sequence Typing

    PubMed Central

    Takahashi, Takashi; Arai, Kazuaki; Lee, Dong-Hyun; Koh, Eun-Ha; Yoshida, Haruno; Yano, Hisakazu; Kaku, Mitsuo

    2016-01-01

    Background We determined the epidemiological characteristics of erythromycin (EM)-resistant Streptococcus pyogenes (group A streptococci, GAS) strains isolated from Korea and Japan, using emm genotyping and multilocus sequence typing (MLST). Methods Clinical isolates of GAS had been collected from 1992 to 2012 in Korea and from 2004 to 2009 in Japan. EM resistance was determined by the microdilution method, and resistance genotypes were assessed by PCR. The emm genotyping and MLST were performed by DNA sequencing. Results The emm genotypes and sequence types (STs) were concordant in 143 (85.1%) of 168 EM-resistant GAS strains from Korea. ST36/emm12 (35.1%), ST52/emm28 (22.6%), and ST49/emm75 (16.1%) were the most common types. Most of the ST36 (93.9%) and ST52 (95.8%) strains harbored erm(B), whereas strains ST49, ST42, and ST15 contained mef(A). The concordance between emm genotypes and STs was 41 (93.2%) among 44 EM-resistant GAS strains from Japan. ST36/emm12 (34.1%), ST49/emm75 (18.2%), and ST28/emm1 (15.9%) were the major types. ST36 isolates harbored either erm(B) (56.3%) or mef(A) (37.5%), whereas isolates ST28, ST49, and ST38 carried only mef(A). The proportion of erm(B) and mef(A) was 66.1% and 33.3% in Korea and 22.7% and 68.2% in Japan, respectively. Conclusions The common STs in Korea and Japan were ST36 and ST49, whereas ST52 was present only in Korea and ST28 only in Japan. Genotype erm(B) was predominant in Korea, whereas mef(A) was frequent in Japan. There were differences between Korea and Japan regarding the frequencies of emm genotypes, STs, and EM resistance genes among the EM-resistant GAS. PMID:26522753

  20. Virulence Gene Pool Detected in Bovine Group C Streptococcus dysgalactiae subsp. dysgalactiae Isolates by Use of a Group A S. pyogenes Virulence Microarray ?

    PubMed Central

    Rato, Mrcia G.; Nerlich, Andreas; Bergmann, Ren; Bexiga, Ricardo; Nunes, Sandro F.; Vilela, Cristina L.; Santos-Sanches, Ilda; Chhatwal, Gursharan S.

    2011-01-01

    A custom-designed microarray containing 220 virulence genes of Streptococcus pyogenes (group A Streptococcus [GAS]) was used to test group C Streptococcus dysgalactiae subsp. dysgalactiae (GCS) field strains causing bovine mastitis and group C or group G Streptococcus dysgalactiae subsp. equisimilis (GCS/GGS) isolates from human infections, with the latter being used for comparative purposes, for the presence of virulence genes. All bovine and all human isolates carried a fraction of the 220 genes (23% and 39%, respectively). The virulence genes encoding streptolysin S, glyceraldehyde-3-phosphate dehydrogenase, the plasminogen-binding M-like protein PAM, and the collagen-like protein SclB were detected in the majority of both bovine and human isolates (94 to 100%). Virulence factors, usually carried by human beta-hemolytic streptococcal pathogens, such as streptokinase, laminin-binding protein, and the C5a peptidase precursor, were detected in all human isolates but not in bovine isolates. Additionally, GAS bacteriophage-associated virulence genes encoding superantigens, DNase, and/or streptodornase were detected in bovine isolates (72%) but not in the human isolates. Determinants located in non-bacteriophage-related mobile elements, such as the gene encoding R28, were detected in all bovine and human isolates. Several virulence genes, including genes of bacteriophage origin, were shown to be expressed by reverse transcriptase PCR (RT-PCR). Phylogenetic analysis of superantigen gene sequences revealed a high level (>98%) of identity among genes of bovine GCS, of the horse pathogen Streptococcus equi subsp. equi, and of the human pathogen GAS. Our findings indicate that alpha-hemolytic bovine GCS, an important mastitis pathogen and considered to be a nonhuman pathogen, carries important virulence factors responsible for virulence and pathogenesis in humans. PMID:21525223

  1. In silico modeling of the type 2 IDI enzymes of Bacillus licheniformis, Pseudomonas stutzeri, Streptococcus pyogenes, and Staphylococcus aureus for virtual screening of potential inhibitors of this therapeutic target.

    PubMed

    Torktaz, Ibrahim; Shahbani Zahiri, Hossein; Akbari Noghabi, Kambiz

    2013-02-01

    Isopentenyl diphosphate isomerase is an essential enzyme in those living organisms such as pathogenic strains of Streptococcus and Staphylococcus genera which rely on the Mevalonate pathway for the production of isoprenoids. The pathogens contain type 2 IDI in contrast to human that contains type 1 IDI. Therefore, the type 2 IDI may be a potential target for the therapy of some infectious diseases. In the current study, a virtual screening by docking was performed among 2000 chemicals from CoCoCo library to find a specific inhibitor for type 2 IDIs. To this end, the structures of the type 2 IDIs of Bacillus licheniformis, Pseudomonas stutzeri, Streptococcus pyogenes, and Staphylococcus aureus were molded using comparative modeling and Hidden Markov Model (HMM) based prediction. The predicted models were evaluated based on Q-mean and Prosa score. Molegro Virtual Docker with MolDock scoring function was used for measuring the binding affinity of the found inhibitor to the active site of the models. Also the inhibition effect of the compound was virtually tested on the crystallography-solved structures of the Sulfolobus shibatae and Thermus thermophilus type 2 IDIs as well as the Escherichia coli type 1 IDI. Finally, the inhibition effect of the found inhibitor was virtually tested on the human type 1 IDI. Interestingly, the results suggest that the inhibitor efficiently binds to and inhibits the bacterial IDIs especially the type 2 IDIs of pathogens while it is not inhibiting the human IDI. PMID:23280415

  2. Pyogenic granuloma

    MedlinePLUS

    Pyogenic granulomas are small, raised, and red bumps on the skin. The bumps have a smooth surface and ... The exact cause of pyogenic granulomas is unknown. They often appear ... arms, or face. Pyogenic granulomas are common in children.

  3. An unusual association of recurrent pyogenic granuloma on nevus flammeus in a patient with Von Recklinghausen's disease.

    PubMed

    Alotaibi, Hend M

    2009-06-01

    Pyogenic granuloma is a common benign vascular lesion of the skin and mucosa. There are a few reports on the rare association between it and port wine stain, but there is no clear description of an association with neurofibromatosis type 1 in the literature. This report presents a 29-year-old Saudi male with Von Recklinghausen's disease with recurrent pyogenic granuloma on the nevus flammeus over his neck. He was treated with shave excision and electrocautery with clearance and no recurrence of pyogenic granuloma for the last 5 years follow-up. PMID:19526173

  4. Dynamics of uterine infections with Escherichia coli, Streptococcus uberis and Trueperella pyogenes in post-partum dairy cows and their association with clinical endometritis.

    PubMed

    Wagener, K; Grunert, T; Prunner, I; Ehling-Schulz, M; Drillich, M

    2014-12-01

    The diversity and dynamics of the uterine microbiota of dairy cows are poorly understood although it is becoming increasingly evident that they play a crucial role in the development of metritis and endometritis. Fourier-transform infrared (FTIR) spectroscopy was used to monitor the bovine microbiota of 40 cows on the day of calving and days 3, 9, 15, and 21 after parturition, and to investigate the associations of selected species with clinical endometritis (CE). Trueperella pyogenes (43.5%), Escherichia coli (21.5%), Bacillus spp. (21.0%) and Streptococcus uberis (18.5%) were the most frequently isolated microbes. Analyses of different sampling time points revealed that the presence of S. uberis on day 3 increased the risk of subsequent T. pyogenes infection on day 9 (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.2-22.6). T. pyogenes infection (OR = 36.0, 95% CI = 3.8-343.2) and retained fetal membranes (RFM) (OR = 12.4, 95%CI = 1.4-112.7) were significant risk factors for CE. Cows with S. uberis on day 3 tended to have greater odds of CE than S. uberis-negative cows (OR = 7.1, 95% CI = 0.9-55.6). Chemometric analysis revealed significant differences in the metabolic profile of S. uberis strains isolated from cows with different vaginal discharge scores. This is the first study showing the association of specific S. uberis subtypes with the uterine health status of post-partum dairy cows. The study demonstrates that uterine clearance is a highly dynamic process, during which time bacteria show distinct patterns of progression, and provides information about interactions between bacterial species involved in the occurrence of CE. PMID:25439441

  5. Substitution of cysteine 192 in a highly conserved Streptococcus pyogenes extracellular cysteine protease (interleukin 1beta convertase) alters proteolytic activity and ablates zymogen processing.

    PubMed Central

    Musser, J M; Stockbauer, K; Kapur, V; Rudgers, G W

    1996-01-01

    Virtually all strains of the human pathogenic bacterium Streptococcus pyogenes express a highly conserved extracellular cysteine protease. The protein is made as an inactive zymogen of 40,000 Da and undergoes autocatalytic truncation to result in a 28,000-Da active protease. Numerous independent lines of investigation suggest that this enzyme participates in one or more phases of host-parasite interaction, such as inflammation and soft tissue invasion. Replacement of the single cysteine residue (C-192) with serine (C192S mutation) resulted in loss of detectable proteolytic activity against bovine casein, human fibronectin, and the low-molecular-weight synthetic substrate 7-amino-4-trifluoromethyl coumarin. The C192S mutant molecule does not undergo autocatalytic processing of zymogen to mature form. Taken together, these data support the hypothesis that C-192 participates in active-site formation and enzyme catalysis. PMID:8675287

  6. Boesenbergia pandurata (Roxb.) Schltr., Eleutherine americana Merr. and Rhodomyrtus tomentosa (Aiton) Hassk. as antibiofilm producing and antiquorum sensing in Streptococcus pyogenes.

    PubMed

    Limsuwan, Surasak; Voravuthikunchai, Supayang Piyawan

    2008-08-01

    Biofilm formation has been demonstrated as a potentially important mechanism contributing to antibiotic treatment failure on Streptococcus pyogenes. It could play a significant role in recurrent and chronic infections. Boesenbergia pandurata (Roxb.) Schltr., Eleutherine americana Merr. and Rhodomyrtus tomentosa (Aiton) Hassk. have been previously reported from our laboratory as effective agents against S. pyogenes. Therefore, in the present study, we observed the effect of these plants on biofilm formation. The bacterial biofilms were quantified by safranin staining and absorbance at 492 nm. The results clearly demonstrated that all subinhibitory concentrations [1/32-1/2 minimal inhibitory concentration (MIC)] of E. americana (7.81-125 microg mL(-1)) and R. tomentosa (0.24-7.81 microg mL(-1)) extracts significantly prevented biofilm formation while 1/2MIC (7.81 microg mL(-1)) of B. pandurata extract produced this effect. The issue of antiquorum sensing of this pathogenic bacterium has been further explored. A correlation between antiquorum-sensing and antibiofilm-producing activities was demonstrated. Strong inhibition on quorum sensing was displayed with the extract of R. tomentosa. Eleutherine americana extract showed partial inhibition, while B. pandurata did not show this activity. By contrast, an assay of microbial adhesion to hydrocarbon revealed no changes in the cell-surface hydrophobicity of the treated organisms. Active organisms with the ability to inhibit quorum sensing and biofilm formation are worth studying as they may provide complimentary medicine for biofilm-associated infections. PMID:18631184

  7. Phage-Like Streptococcus pyogenes Chromosomal Islands (SpyCI) and Mutator Phenotypes: Control by Growth State and Rescue by a SpyCI-Encoded Promoter.

    PubMed

    Scott, Julie; Nguyen, Scott V; King, Catherine J; Hendrickson, Christina; McShan, W Michael

    2012-01-01

    We recently showed that a prophage-like Streptococcus pyogenes chromosomal island (SpyCI) controls DNA mismatch repair and other repair functions in M1 genome strain SF370 by dynamic excision and reintegration into the 5' end of mutL in response to growth, causing the cell to alternate between a wild type and mutator phenotype. Nine of the 16 completed S. pyogenes genomes contain related SpyCI integrated into the identical attachment site in mutL, and in this study we examined a number of these strains to determine whether they also had a mutator phenotype as in SF370. With the exception of M5 genome strain Manfredo, all demonstrated a mutator phenotype as compared to SpyCI-free strain NZ131. The integrase gene (int) in the SpyCIM5 contains a deletion that rendered it inactive, and this deletion predicts that Manfredo would have a pronounced mutator phenotype. Remarkably, this was found not to be the case, but rather a cryptic promoter within the int ORF was identified that ensured constitutive expression of mutL and the downstream genes encoded on the same mRNA, providing a striking example of rescue of gene function following decay of a mobile genetic element. The frequent occurrence of SpyCI in the group A streptococci may facilitate bacterial survival by conferring an inducible mutator phenotype that promotes adaptation in the face of environmental challenges or host immunity. PMID:22969756

  8. Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System.

    PubMed

    Ka, Donghyun; Lee, Hasup; Jung, Yi-Deun; Kim, Kyunggon; Seok, Chaok; Suh, Nayoung; Bae, Euiyoung

    2016-01-01

    CRISPRs and Cas proteins constitute an RNA-guided microbial immune system against invading nucleic acids. Cas1 is a universal Cas protein found in all three types of CRISPR-Cas systems, and itsrole is implicated in new spacer acquisition duringCRISPR-mediated adaptive immunity. Here, we report the crystal structure of Streptococcus pyogenes Cas1 (SpCas1) in a type II CRISPR-Cas system and characterize its interaction with S.pyogenes Csn2 (SpCsn2). The SpCas1 structure reveals a unique conformational state distinct from type I Cas1 structures, resulting in a more extensive dimerization interface, a more globular overall structure, and a disruption of potential metal-binding sites for catalysis. We demonstrate that SpCas1 directly interacts with SpCsn2, and identify the binding interface and key residues for Cas complex formation. These results provide structural information for a type II Cas1 protein, and lay a foundation for studying multiprotein Cas complexes functioning in type II CRISPR-Cas systems. PMID:26671707

  9. Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes

    PubMed Central

    Scocchera, Eric W.; Martin, Brooke D.; Swain III, P. Whitney; Alverson, Jeremy B.; Priestley, Nigel D.; Anderson, Amy C.; Wright, Dennis L.

    2012-01-01

    Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin. PMID:22347365

  10. In vitro activity of antimicrobial agents against streptococcus pyogenes isolated from different regions of Khyber PakhtunKhwa Pakistan.

    PubMed

    Rizwan, Muhammad; Bakht, Jehan; Bacha, Nafees; Ahmad, Bashir

    2016-01-01

    The present study investigates the antibiotic resistance of S. pyogenes of 600 isolates collected from different body parts including throat and sputum were analyzed for their antimicrobial susceptibility to 5 antibiotics using the Kirby Bauer disc diffusion method. Based on different identification tests including, gram staining, beta hemolysis, catalase test and bacitracin sensitivity test, a total of 138 isolates were confirmed as S. pyogenes. The prevalence of S. pyogenes was 80% in sore throat and 29% in sputum samples. These isolates were further tested for antibiotics resistance using disk diffusion method. Out of 138 isolates, 49.27% isolates showed resistance towards cefixime, 28.98% towards cefotaxime and 17.39% towards ciprofloxacin, 17.39% towards ampicillin, 17.39% towards erythromycin, 15.94% towards streptomycin, 0.724% isolates towards chloromphenicol and 0% towards penicillin. Among the resistant isolates of S. pyogenes, 60.71% showed resistance towards cefixime, 57.14% towards ciprofloxacin, 57.14% towards streptomycin, 50% towards erythromycin and 25% towards cefotaxime. PMID:26826819

  11. The Histone-Like Protein Hlp Is Essential for Growth of Streptococcus pyogenes: Comparison of Genetic Approaches To Study Essential Genes?

    PubMed Central

    Bugrysheva, Julia V.; Froehlich, Barbara J.; Freiberg, Jeffrey A.; Scott, June R.

    2011-01-01

    Selection of possible targets for vaccine and drug development requires an understanding of the physiology of bacterial pathogens, for which the ability to manipulate expression of essential genes is critical. For Streptococcus pyogenes (the group A streptococcus [GAS]), an important human pathogen, the lack of genetic tools for such studies has seriously hampered research. To address this problem, we characterized variants of the inducible Ptet cassette, in both sense and antisense contexts, as tools to regulate transcription from GAS genes. We found that although the three-operator Ptet construct [Ptet(O)3] had low uninduced expression, its induction level was low, while the two-operator construct [Ptet(O)2] was inducible to a high level but showed significant constitutive expression. Use of Ptet(O)3 in the chromosome allowed us to demonstrate previously that RNases J1 and J2 are required for growth of GAS. Here we report that the uninduced level from the chromosomally inserted Ptet(O)2 construct was too high for us to observe differential growth. For the highly expressed histone-like protein (Hlp) of GAS, neither chromosomal insertion of Ptet(O)2 or Ptet(O)3 nor their use on a high-copy-number plasmid to produce antisense RNA specific to hlp resulted in adequate differential expression. However, by replacing the ribosome binding site of hlp with an engineered riboswitch to control translation of Hlp, we demonstrated for the first time that this protein is essential for GAS growth. PMID:21531823

  12. Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle.

    PubMed

    Amos, Matthew R; Healey, Gareth D; Goldstone, Robert J; Mahan, Suman M; Düvel, Anna; Schuberth, Hans-Joachim; Sandra, Olivier; Zieger, Peter; Dieuzy-Labaye, Isabelle; Smith, David G E; Sheldon, Iain Martin

    2014-03-01

    Purulent disease of the uterus develops in 40% of dairy cows after parturition, when the epithelium of the endometrium is disrupted to expose the underlying stroma to bacteria. The severity of endometrial pathology is associated with isolation of Trueperella pyogenes. In the present study, T. pyogenes alone caused uterine disease when infused into the uterus of cattle where the endometrial epithelium was disrupted. The bacterium secretes a cholesterol-dependent cytolysin, pyolysin (PLO), and the plo gene was identical and the plo gene promoter was highly similar amongst 12 clinical isolates of T. pyogenes. Bacteria-free filtrates of the T. pyogenes cultures caused hemolysis and endometrial cytolysis, and PLO was the main cytolytic agent, because addition of anti-PLO antibody prevented cytolysis. Similarly, a plo-deletion T. pyogenes mutant did not cause hemolysis or endometrial cytolysis. Endometrial stromal cells were notably more sensitive to PLO-mediated cytolysis than epithelial or immune cells. Stromal cells also contained more cholesterol than epithelial cells, and reducing stromal cell cholesterol content using cyclodextrins protected against PLO. Although T. pyogenes or plo-deletion T. pyogenes stimulated accumulation of inflammatory mediators, such as IL-1beta, IL-6, and IL-8, from endometrium, PLO did not stimulate inflammatory responses by endometrial or hematopoietic cells, or in vitro organ cultures of endometrium. The marked sensitivity of stromal cells to PLO-mediated cytolysis provides an explanation for how T. pyogenes acts as an opportunistic pathogen to cause pathology of the endometrium once the protective epithelium is lost after parturition. PMID:24478394

  13. Elimination of Chromosomal Island SpyCIM1 from Streptococcus pyogenes Strain SF370 Reverses the Mutator Phenotype and Alters Global Transcription

    PubMed Central

    Nguyen, Scott V.; Rahman, Maliha; McCullor, Kimberly A.; King, Catherine J.; Fischetti, Vincent A.; McShan, W. Michael

    2015-01-01

    Streptococcus pyogenes chromosomal island M1 (SpyCIM1) integrates by site-specific recombination into the 5’ end of DNA mismatch repair (MMR) gene mutL in strain SF370SmR, blocking transcription of it and the downstream operon genes. During exponential growth, SpyCIM1 excises from the chromosome and replicates as an episome, restoring mutL transcription. This process is reversed in stationary phase with SpyCIM1 re-integrating into mutL, returning the cells to a mutator phenotype. Here we show that elimination of SpyCIM1 relieves this mutator phenotype. The downstream MMR operon genes, multidrug efflux pump lmrP, Holliday junction resolution helicase ruvA, and DNA base excision repair glycosylase tag, are also restored to constitutive expression by elimination of SpyCIM1. The presence of SpyCIM1 alters global transcription patterns in SF370SmR. RNA sequencing (RNA-Seq) demonstrated that loss of SpyCIM1 in the SpyCIM1 deletion mutant, CEM1Δ4, impacted the expression of over 100 genes involved in virulence and metabolism both in early exponential phase, when the SpyCIM1 is episomal, as well as at the onset of stationary phase, when SpyCIM1 has reintegrated into mutL. Among these changes, the up-regulation of the genes for the antiphagocytic M protein (emm1), streptolysin O (slo), capsule operon (hasABC), and streptococcal pyrogenic exotoxin (speB), are particularly notable. The expression pattern of the MMR operon confirmed our earlier observations that these genes are transcribed in early exponential phase but silenced as stationary phase is approached. Thus, the direct role of SpyCIM1 in causing the mutator phenotype is confirmed, and further, its influence upon the biology of S. pyogenes was found to impact multiple genes in addition to the MMR operon, which is a novel function for a mobile genetic element. We suggest that such chromosomal islands are a remarkable evolutionary adaptation to promote the survival of its S. pyogenes host cell in changing environments. PMID:26701803

  14. Evaluation of the antimicrobial efficacy of green tea extract (egcg) against streptococcus pyogenes in vitro - biomed 2011.

    PubMed

    Hull Vance, Stacy; Tucci, Michelle; Benghuzzi, Hamed

    2011-01-01

    S. pyogenes (GAS) is the agent that is involved in acute infections that can lead to devastating life-threatening invasive infections. S. pyogenes cell-surface components such as lipoteichoic acid, hyaluronic acid capsule, M proteins, and laminin and collagen binding proteins are responsible for adhesion to human cells. Natural compounds have been associated with decreased adherence of bacteria to cells. The most widely studies of these compounds has been cranberry juice which is thought to disrupt cellular adherence by altering the local cellular. The purpose of this study was to determine if pre-treating or post-treating kidney epithelial cells (RMKEC) with Epigallocatechin Gallate (EGCG) alters GAS?s ability to adhere to the host cells. Our data indicates that pretreating or post treating the cells with EGCG (10M, 30M, or 50M) inhibited the attachment of the bacteria to the cells in a dose dependent manner. The results also indicate that the remaining GAS bacteria attached to the cellular surface after a 24 hour period was unable to penetrate the epithelial cells. Additional studies also showed EGCG has antimicrobial properties at various concentrations. Our results indicate that EGCG can effectively reduce GAS bacteria cellular attachment and induce GAS cell death and can be used effectively as an adjunct to conventional antibiotic treatments. PMID:21525617

  15. Cleavage of interleukin 1 beta (IL-1 beta) precursor to produce active IL-1 beta by a conserved extracellular cysteine protease from Streptococcus pyogenes.

    PubMed Central

    Kapur, V; Majesky, M W; Li, L L; Black, R A; Musser, J M

    1993-01-01

    Streptococcal pyrogenic exotoxin B (SPE B), a conserved extracellular cysteine protease expressed by the human pathogenic bacterium Streptococcus pyogenes, was purified and shown to cleave inactive human interleukin 1 beta precursor (pIL-1 beta) to produce biologically active IL-1 beta. SPE B cleaves pIL-1 beta one residue amino-terminal to the site where a recently characterized endogenous human cysteine protease acts. IL-1 beta resulting from cleavage of pIL-1 beta by SPE B induced nitric oxide synthase activity in vascular smooth muscle cells and killed of the human melanoma A375 line. Two additional naturally occurring SPE B variants cleaved pIL-1 beta in a similar fashion. By demonstrating that SPE B catalyzes the formation of biologically active IL-1 beta from inactive pIL-1 beta, our data add a further dimension to an emerging theme in microbial pathogenesis that bacterial and viral virulence factors act directly on host cytokine pathways. The data also contribute to an enlarging literature demonstrating that microbial extracellular cysteine proteases are important in host-parasite interactions. Images Fig. 1 Fig. 2 Fig. 4 PMID:7689226

  16. Antibacterial resistance in Streptococcus pyogenes (GAS) from healthy carriers and tonsillitis patients and association with antibacterial sale in the Faroe Islands.

    PubMed

    Magnussen, Marita D; Gaini, Shahin; Gislason, Hannes; Kristinsson, Karl G

    2016-04-01

    The aim of this study was to investigate the antibacterial resistance of Streptococcus pyogenes (GAS), and correlate the findings with the sales of erythromycin and tetracycline. General practitioners in the Faroe Islands were recruited to send oropharyngeal swabs. From an ongoing pneumococcal study, nasopharyngeal swabs were sampled from healthy children 0-7 years of age. Erythromycin susceptibility data from Iceland were obtained from the reference laboratory at the Landspitali University Hospital. Susceptibility testing in the Faroe Islands and Iceland was performed according to CLSI methods and criteria. The resistance rate to erythromycin and tetracycline found in patients in the Faroe Islands in 2009/2010 was 6% and 30% respectively. Tetracycline resistance in patients declined significantly from 2009 to 2010 (37-10%, p-value = 0.006 < 0.05) and differed significantly between age groups (p-value = 0.03 < 0.05). In Iceland, there was a peak in erythromycin resistance in 2008 (44%) and a substantial decrease in 2009 (5%). Although the prevalence of erythromycin and tetracycline resistance in the Faroe Islands and Iceland may be associated with antimicrobial use, sudden changes can occur with the introduction of new resistant clones. PMID:26833774

  17. Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop

    SciTech Connect

    González-Páez, Gonzalo E.; Wolan, Dennis W.

    2012-09-05

    Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 {angstrom} resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC{sub 50} values for trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.

  18. Effects of penicillin and erythromycin on adherence of invasive and noninvasive isolates of Streptococcus pyogenes to laminin

    PubMed Central

    mitran, Aleksandra; Vukovi?, Dragana; Gaji?, Ina; Marinkovi?, Jelena; Ranin, Lazar

    2015-01-01

    This study investigated the possible relationship between the invasiveness of group A Streptococcus (GAS) strains and their abilities to adhere to laminin and assessed the effects of subinhibitory concentrations of penicillin and erythromycin on the ability of GAS to adhere to laminin. The adherence of noninvasive and highly invasive isolates of GAS to laminin was significantly higher than the adherence displayed by isolates of low invasiveness. Antibiotic treatment caused significant reductions in adherence to laminin in all three groups of strains. Penicillin was more successful in reducing the adherence abilities of the tested GAS strains than erythromycin. PMID:26270594

  19. Increased Risk of Pyogenic Liver Abscess Among Patients With Colonic Diverticular Diseases: A Nationwide Cohort Study.

    PubMed

    Tsai, Ming-Shian; Lee, Hui-Ming; Hsin, Ming-Che; Lin, Cheng-Li; Hsu, Chung-Y; Liu, Yen-Tze; Kao, Chia-Hung

    2015-12-01

    Whether patients with diverticular diseases exhibit a higher risk of developing pyogenic liver abscess (PLA) remains inconclusive.From the inpatient claims in Taiwan's National Health Insurance Research Database, we identified 54,147 patients diagnosed with diverticulosis in the 1998 to 2010 period and 216,588 controls without the disorder. The 2 cohorts were matched by age, sex, and admission year, and were followed up until the end of 2010 to estimate the risk of PLA.Overall, the incidence of PLA was 2.44-fold higher in the diverticular-disease group than in the controls (11.5 vs 4.65 per 10,000 person-year). The adjusted hazard ratio (aHR) of PLA was 2.11 (95% confidence interval [CI], 1.81-2.44) for the diverticular-disease group, according to a multivariate Cox proportional hazards regression model. The age-specific data showed that the aHR for the diverticular-disease group, compared with the controls, was the highest inpatients younger than 50 years old (aHR, 4.03; 95% CI, 2.77-5.85). Further analysis showed that the diverticular-disease group exhibited an elevated risk of PLA regardless of whether patients had diverticulitis.The patients with diverticular diseases exhibited a higher risk of PLA. PMID:26656355

  20. The Streptococcus pyogenes orphan protein tyrosine phosphatase, SP-PTP, possesses dual specificity and essential virulence regulatory functions.

    PubMed

    Kant, Sashi; Agarwal, Shivani; Pancholi, Preeti; Pancholi, Vijay

    2015-08-01

    Group A Streptococcus (GAS) is a human pathogen that causes high morbidity and mortality. GAS lacks a gene encoding tyrosine kinase but contains one encoding tyrosine phosphatase (SP-PTP). Thus, GAS is thought to lack tyrosine phosphorylation, and the physiological significance of SP-PTP is, therefore, questionable. Here, we demonstrate that SP-PTP possesses dual phosphatase specificity for Tyr- and Ser/Thr-phosphorylated GAS proteins, such as Ser/Thr kinase (SP-STK) and the SP-STK-phosphorylated CovR and WalR proteins. Phenotypic analysis of GAS mutants lacking SP-PTP revealed that the phosphatase activity per se positively regulates growth, cell division and the ability to adhere to and invade host cells. Furthermore, A549 human lung cells infected with GAS mutants lacking SP-PTP displayed increased Ser-/Thr-/Tyr-phosphorylation. SP-PTP also differentially regulates the expression of ?50% of the total GAS genes, including several virulence genes potentially through the two-component regulators, CovR, WalR and PTS/HPr regulation of Mga. Although these mutants exhibit attenuated virulence, a GAS mutant overexpressing SP-PTP is hypervirulent. Our study provides the first definitive evidence for the presence and importance of Tyr-phosphorylation in GAS and the relevance of SP-PTP as an important therapeutic target. PMID:25939957

  1. Extracellular Cysteine Protease Produced by Streptococcus pyogenes Participates in the Pathogenesis of Invasive Skin Infection and Dissemination in Mice

    PubMed Central

    Lukomski, Slawomir; Montgomery, Charles A.; Rurangirwa, Jacqueline; Geske, Robert S.; Barrish, James P.; Adams, Gerald J.; Musser, James M.

    1999-01-01

    The role of an extracellular cysteine protease encoded by the speB gene in group A Streptococcus (GAS) skin infection was studied with a mouse model. Mice were injected subcutaneously with a wild-type GAS serotype M3 strain or a cysteine protease-inactivated isogenic derivative grown to stationary phase. The mortality rate of mice injected with the M3 speB mutant strain was significantly decreased (P < 0.0008) compared to that of animals injected with the wild-type parental organism. The abscesses formed in animals infected with the cysteine protease mutant strain were significantly smaller (P < 0.0001) than those caused by the wild-type organism and slowly regressed over 3 to 4 weeks. In striking contrast, infection with the wild-type GAS isolate generated necrotic lesions, and in some animals the GAS disseminated widely from the injection site and produced extensive cutaneous damage. All of these animals developed bacteremia and died. GAS dissemination was accompanied by severe tissue and blood vessel necrosis. Cysteine protease expression in the infected tissue was identified by immunogold electron microscopy. These data demonstrate that cysteine protease expression contributes to soft tissue pathology, including necrosis, and is required for efficient systemic dissemination of the organism from the initial site of skin inoculation. PMID:10085018

  2. Adhesin competence repressor (AdcR) from Streptococcus pyogenes controls adaptive responses to zinc limitation and contributes to virulence

    PubMed Central

    Sanson, Misu; Makthal, Nishanth; Flores, Anthony R.; Olsen, Randall J.; Musser, James M.; Kumaraswami, Muthiah

    2015-01-01

    Altering zinc bioavailability to bacterial pathogens is a key component of host innate immunity. Thus, the ability to sense and adapt to the alterations in zinc concentrations is critical for bacterial survival and pathogenesis. To understand the adaptive responses of group A Streptococcus (GAS) to zinc limitation and its regulation by AdcR, we characterized gene regulation by AdcR. AdcR regulates the expression of 70 genes involved in zinc acquisition and virulence. Zinc-bound AdcR interacts with operator sequences in the negatively regulated promoters and mediates differential regulation of target genes in response to zinc deficiency. Genes involved in zinc mobilization and conservation are derepressed during mild zinc deficiency, whereas the energy-dependent zinc importers are upregulated during severe zinc deficiency. Further, we demonstrated that transcription activation by AdcR occurs by direct binding to the promoter. However, the repression and activation by AdcR is mediated by its interactions with two distinct operator sequences. Finally, mutational analysis of the metal ligands of AdcR caused impaired DNA binding and attenuated virulence, indicating that zinc sensing by AdcR is critical for GAS pathogenesis. Together, we demonstrate that AdcR regulates GAS adaptive responses to zinc limitation and identify molecular components required for GAS survival during zinc deficiency. PMID:25510500

  3. Streptococcus pyogenes emm Types and Clusters during a 7-Year Period (2007 to 2013) in Pharyngeal and Nonpharyngeal Pediatric Isolates

    PubMed Central

    Koutouzi, F.; Tsakris, A.; Chatzichristou, P.; Koutouzis, E.; Daikos, G. L.; Kirikou, E.; Petropoulou, N.; Syriopoulou, V.

    2015-01-01

    Group A streptococcus (GAS) is an important cause of morbidity and mortality worldwide. Surveillance of emm types has important implications, as it can provide baseline information for possible implementation of vaccination. A total of 1,349 GAS pediatric isolates were collected during a 7-year period (2007 to 2013); emm typing was completed for 1,282 pharyngeal (84%) or nonpharyngeal (16%) isolates, and emm clusters and temporal changes were analyzed. Thirty-five different emm types, including 14 subtypes, were identified. The most prevalent emm types identified were 1 (16.7%), 12 (13.6%), 77 (10.9%), 4 (10.8%), 28 (10.4%), 6 (6.8%), 3 (6.6%), and 89 (6.6%), accounting for 82.3% of total isolates. Rheumatogenic emm types comprised 16.3% of total isolates. The emm types 12, 4, and 77 were more prevalent among pharyngeal isolates, and the emm types 1, 89, 6, 75, and 11 were more prevalent among nonpharyngeal isolates. The emm types identified belonged to 13 emm clusters, and the 8 most prevalent clusters comprised 97% of all isolates. There were statistically significant decreases in the prevalence of emm types 12, 4, 5, and 61 and increases in the prevalence of emm types 89, 75, and 11, compared with the period 2001 to 2006. The proposed 30-valent GAS vaccine, which is currently in preclinical studies, encompasses 97.2% of the emm types detected in our study and 97.4% of the erythromycin-resistant strains. In addition, it includes 93.3% of the emm types involved in bacteremia. A much greater diversity of GAS emm types was identified in our area than described previously. Seasonal fluctuations and the introduction of new emm types were observed. Continuous surveillance of emm types is needed in order to evaluate the possible benefits of an M protein-based GAS vaccine. PMID:25878351

  4. Antibody levels and in vitro lymphoproliferative responses to Streptococcus pyogenes erythrogenic toxin A and mitogen of patients with rheumatic fever.

    PubMed Central

    Bahr, G M; Yousof, A M; Behbehani, K; Majeed, H A; Sakkalah, S; Souan, K; Jarrad, I; Geoffroy, C; Alouf, J E

    1991-01-01

    We investigated the in vitro lymphoproliferative responses to a streptococcal mitogen and erythrogenic toxin A of children with acute rheumatic fever (ARF) and patients with chronic rheumatic heart disease (CRHD). Antibody levels to the streptococcal products were also analyzed in the sera of those with ARF or chronic rheumatic heart disease as well as in the sera of children with streptococcal pharyngitis or poststreptococcal glomerulonephritis. Our results demonstrated that the individuals had depressed lymphoproliferative responses during the active stage of rheumatic fever. The depressed responses were not found either to be induced by time-sensitive mitogen-specific suppressor cells or to be related to a dose-response phenomenon. On the other hand, antibody levels to the extracellular mitogens were significantly elevated in the sera of children with ARF compared with the levels in the rest of the groups. The hyperresponsiveness noted among children with ARF was found to be at a quantitative level and was not due to recognition of more epitopes, as determined by Western blotting (immunoblotting). The profile of immune responsiveness in children with ARF to the streptococcal extracellular mitogens is discussed in relation to the pathogenesis of disease. Images PMID:1774298

  5. Epethelial Presence of Trueperella pyogenes Predicts Site-Level Presence of Cranial Abscess Disease in White-Tailed Deer (Odocoileus virginianus)

    PubMed Central

    Belser, Emily H.; Cohen, Bradley S.; Keeler, Shamus P.; Killmaster, Charles H.; Bowers, John W.; Miller, Karl V.

    2015-01-01

    Cranial/intracranial abscess disease is an emerging source of significant mortality for male white-tailed deer (Odocoileus virginianus). Most cases of cranial/intracranial abscess disease are associated with infection by the opportunistic pathogen Trueperella pyogenes although the relationship between the prevalence of the bacteria and occurrence of disease is speculative. We examined 5,612 hunter-harvested deer from 29 sites across all physiographic provinces in Georgia for evidence of cranial abscess disease and sampled the forehead, lingual, and nasal surfaces from 692 deer. We used polymerase chain reaction (PCR) to determine presence of T. pyogenes from these samples. We found T. pyogenes prevalence at a site was a predictor for the occurrence of cranial abscess disease. Prevalence of T. pyogenes did not differ between samples from the nose or tongue although prevalence along the forehead was greater for males than females (p = 0.04), particularly at sites with high occurrence of this disease. Socio-sexual behaviors, bacterial prevalence, or physiological characteristics may predispose male deer to intracranial/cranial abscess disease. Determination of factors that affect T. pyogenes prevalence among sites may help explain the occurrence of this disease among populations. PMID:25803047

  6. Epethelial presence of Trueperella pyogenes predicts site-level presence of cranial abscess disease in white-tailed deer (Odocoileus virginianus).

    PubMed

    Belser, Emily H; Cohen, Bradley S; Keeler, Shamus P; Killmaster, Charles H; Bowers, John W; Miller, Karl V

    2015-01-01

    Cranial/intracranial abscess disease is an emerging source of significant mortality for male white-tailed deer (Odocoileus virginianus). Most cases of cranial/intracranial abscess disease are associated with infection by the opportunistic pathogen Trueperella pyogenes although the relationship between the prevalence of the bacteria and occurrence of disease is speculative. We examined 5,612 hunter-harvested deer from 29 sites across all physiographic provinces in Georgia for evidence of cranial abscess disease and sampled the forehead, lingual, and nasal surfaces from 692 deer. We used polymerase chain reaction (PCR) to determine presence of T. pyogenes from these samples. We found T. pyogenes prevalence at a site was a predictor for the occurrence of cranial abscess disease. Prevalence of T. pyogenes did not differ between samples from the nose or tongue although prevalence along the forehead was greater for males than females (p = 0.04), particularly at sites with high occurrence of this disease. Socio-sexual behaviors, bacterial prevalence, or physiological characteristics may predispose male deer to intracranial/cranial abscess disease. Determination of factors that affect T. pyogenes prevalence among sites may help explain the occurrence of this disease among populations. PMID:25803047

  7. Consequences of the variability of the CovRS and RopB regulators among Streptococcus pyogenes causing human infections

    PubMed Central

    Fries, Ana; Pato, Catarina; Melo-Cristino, Jos; Ramirez, Mario

    2015-01-01

    To evaluate the importance of covRS and ropB mutations in invasive disease caused by Group A Streptococci (GAS), we determined the sequence of the covRS and ropB genes of 191 isolates from invasive infections and pharyngitis, comprising a diverse set of emm types and multilocus sequence types. The production of SpeB and the activity of NAD glycohydrolase (NADase) and streptolysin S (SLS) were evaluated. The results support the acquisition of null covS alleles (predicted to eliminate protein function), resulting in downregulation of SpeB and upregulation of NADase and SLS, as a mechanism possibly contributing to higher invasiveness. Among the isolates tested, this mechanism was found to be uncommon (10% of invasive isolates) and was not more prevalent among clones with enhanced invasiveness (including M1T1) but occurred in diverse genetic backgrounds. In lineages such as emm64, these changes did not result in upregulation of NADase and SLS, highlighting the diversity of regulatory pathways in GAS. Despite abrogating SpeB production, null alleles in ropB were not associated with invasive infection. The covRS and ropB genes are under stabilising selection and no expansion of isolates carrying null alleles has been observed, suggesting that the presence of these regulators is important for overall fitness. PMID:26174161

  8. Highly Effective Renaturation of a Streptokinase from Streptococcus pyogenes DT7 as Inclusion Bodies Overexpressed in Escherichia coli

    PubMed Central

    Nguyen, Sy Le Thanh; Quyen, Dinh Thi; Vu, Hong Diep

    2014-01-01

    The streptokinase (SK) is emerging as an important thrombolytic therapy agent in the treatment of patients suffering from cardiovascular diseases. We reported highly effective renaturation of a SK from S. pyogeness DT7 overexpressed in E. coli, purification, and biochemical characterization. A gene coding for the SK was cloned from S. pyogeness DT7. Because accumulation of active SK is toxic to the host cells, we have expressed it in the form of inclusion bodies. The mature protein was overexpressed in E. coli BL21 DE3/pESK under the control of the strong promoter tac induced by IPTG with a level of 60% of the total cell proteins. The activity of the rSK, renatured in phosphate buffer supplemented with Triton X-100 and glycerol, was covered with up to 41 folds of its initial activity. The purified of protein was identified with MALDI-TOF mass spectrometry through four peptide fragments, which showed 100% identification to the corresponding peptides of the putative SK from GenBank. Due to overexpression and highly effective renaturation of large amounts of inclusion bodies, the recombinant E. coli BL21 DE3/pESK system could be potentially applied for large-scale production of SK used in the therapy of acute myocardial infarction. PMID:24883307

  9. Virulence Gene Regulation by CvfA, a Putative RNase: the CvfA-Enolase Complex in Streptococcus pyogenes Links Nutritional Stress, Growth-Phase Control, and Virulence Gene Expression?

    PubMed Central

    Kang, Song Ok; Caparon, Michael G.; Cho, Kyu Hong

    2010-01-01

    Streptococcus pyogenes, a multiple-auxotrophic human pathogen, regulates virulence gene expression according to nutritional availability during various stages in the infection process or in different infection sites. We discovered that CvfA influenced the expression of virulence genes according to growth phase and nutritional status. The influence of CvfA in C medium, rich in peptides and poor in carbohydrates, was most pronounced at the stationary phase. Under these conditions, up to 30% of the transcriptome exhibited altered expression; the levels of expression of multiple virulence genes were altered, including the genes encoding streptokinase, CAMP factor, streptolysin O, M protein (more abundant in the CvfA? mutant), SpeB, mitogenic factor, and streptolysin S (less abundant). The increase of carbohydrates or peptides in media restored the levels of expression of the virulence genes in the CvfA? mutant to wild-type levels (emm, ska, and cfa by carbohydrates; speB by peptides). Even though the regulation of gene expression dependent on nutritional stress is commonly linked to the stringent response, the levels of ppGpp were not altered by deletion of cvfA. Instead, CvfA interacted with enolase, implying that CvfA, a putative RNase, controls the transcript decay rates of virulence factors or their regulators according to nutritional status. The virulence of CvfA? mutants was highly attenuated in murine models, indicating that CvfA-mediated gene regulation is necessary for the pathogenesis of S. pyogenes. Taken together, the CvfA-enolase complex in S. pyogenes is involved in the regulation of virulence gene expression by controlling RNA degradation according to nutritional stress. PMID:20385762

  10. Nucleotide sequence of conjugative prophage Φ1207.3 (formerly Tn1207.3) carrying the mef(A)/msr(D) genes for efflux resistance to macrolides in Streptococcus pyogenes.

    PubMed

    Iannelli, Francesco; Santagati, Maria; Santoro, Francesco; Oggioni, Marco R; Stefani, Stefania; Pozzi, Gianni

    2014-01-01

    Genetic element Φ1207.3 (formerly Tn1207.3) is a prophage of Streptococcus pyogenes which carries the macrolide efflux resistance genes mef(A)/msr(D) and is capable of conjugal transfer among streptococci. Complete nucleotide sequence showed that Φ1207.3 is 52,491 bp in length and contained 58 open reading frames (ORFs). A manual homology-based annotation with functional prediction of the hypothetical gene product was possible only for 34 out of 58 ORFs. Φ1207.3 codes for two different C-methylation systems, several phage structural genes, a lysis cassette (composed by a holin and a peptidoglycan hydrolase), and three site-specific resolvases of the serine recombinase family. PMID:25538698

  11. Horizontal gene transfer and recombination in Streptococcus dysgalactiae subsp. equisimilis

    PubMed Central

    McNeilly, Celia L.; McMillan, David J.

    2014-01-01

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a human pathogen that colonizes the skin or throat, and causes a range of diseases from relatively benign pharyngitis to potentially fatal invasive diseases. While not as virulent as the close relative Streptococcus pyogenes the two share a number of virulence factors and are known to coexist in a human host. Both pre- and post-genomic studies have revealed that horizontal gene transfer (HGT) and recombination occurs between these two organisms and plays a major role in shaping the population structure of SDSE. This review summarizes our current knowledge of HGT and recombination in the evolution of SDSE. PMID:25566202

  12. In silico and in vitro studies of cinnamaldehyde and their derivatives against LuxS in Streptococcus pyogenes: effects on biofilm and virulence genes.

    PubMed

    Beema Shafreen, Raja Mohmed; Selvaraj, Chandrabose; Singh, Sanjeev Kumar; Karutha Pandian, Shunmugiah

    2014-02-01

    The LuxS-based signalling pathway has an important role in physiological and pathogenic functions that are capable of causing different infections. In the present study, cinnamaldehyde (CN) and their derivatives were evaluated for their inhibitory efficiency against LuxS by molecular modelling, docking, dynamics and free-energy calculations. Sequence and structure-similarity analysis of LuxS protein, five different amino acids were found to be highly conserved, of which GLY128 was identified as the key residue involved in the effective binding of the ligands. Quantum-polarized ligand docking protocol showed that 2nitro and 4nitro CN has a higher binding efficiency than CN, which very well corroborates with the in vitro studies. COMSTAT analysis for the microscopic images of the S. pyogenes biofilm showed that the ligands have antibiofilm potential. In addition, the results of quantitative polymerase chain reaction (qPCR) analysis revealed that the transcripts treated with the compounds showed decrease in luxS expression, which directly reflects with the reduction in expression of speB. No substantial effect was observed on the virulence regulator (srv) transcript. These results confirm that speB is controlled by the regulation of luxS. The decreased rate of S. pyogenes survival in the presence of these ligands envisaged the fact that the compounds could readily enhance opsonophagocytosis with the reduction of virulence factor secretion. Thus, the overall data supports the use of CN derivatives against quorum sensing-mediated infections caused by S. pyogenes. PMID:24436128

  13. Health care associated hematogenous pyogenic vertebral osteomyelitis: a severe and potentially preventable infectious disease.

    PubMed

    Pigrau, Carlos; Rodríguez-Pardo, Dolors; Fernández-Hidalgo, Nuria; Moretó, Laura; Pellise, Ferran; Larrosa, Maria-Nieves; Puig, Mireia; Almirante, Benito

    2015-01-01

    Although hematogenous pyogenic spinal infections have been related to hemodialysis (HD), catheter-related sepsis, and sporadically, to other nosocomial infections or procedures, in most recent studies and reviews the impact of nosocomial infection as a risk factor for vertebral osteomyelitis (VO) is not well established. The aim of our study was to describe the risk factors, infectious source, etiology, clinical features, therapy, and outcome of health care associated VO (HCAVO), and compare them with community-acquired VO (CAVO) cases.A retrospective cohort study of consecutive patients with hematogenous VO was conducted in our third-level hospital between 1987 and 2011. HCAVO was defined as onset of symptoms after 1 month of hospitalization or within 6 months after hospital discharge, or ambulatory manipulations in the 6 months before the diagnosis.Over the 25-year study period, among 163 hematogenous pyogenic VO, 41 (25%) were health care associated, a percentage that increased from 15% (9/61) in the 1987-1999 period to 31% (32/102) in the 2000-2011 period (P < 0.01). The presumed source of infection was an intravenous catheter in 14 (34%), cutaneous foci in 8 (20%), urinary tract in 7 (17%), gastrointestinal in 3 (7%), other foci in 3 (7%), and unknown in 6 (15%). Staphylococcus aureus was the most frequently isolated microorganism (14 cases, 34%), followed by coagulase-negative Staphylococci (CoNS) in 6 (15%), and Enterobacteriaceae in 6 (15%) cases.Compared with CAVO cases, patients with HCAVO were older (mean 66.0 SD 13.0 years vs 60.5 SD 15.5 years), had more underlying conditions (73% vs 50%, P < 0.05), neoplasm/immunosuppression (39% vs 7%, P < 0.005), chronic renal failure (19% vs 4%, P < 0.001), a known source of infection (85% vs 54% P < 0.05), Candida spp (7% vs 0%, P < 0.01) or CoNS infections (15% vs 2%, P < 0.05), higher mortality (15% vs 6%, P = 0.069), and a higher relapse rate in survivors (9% vs 1%, P < 0.05).Presently, in our setting, one-third of hematogenous pyogenic VO infections are health care associated, and a third of these are potentially preventable catheter-related infections. Compared with CAVO, in health care associated hematogenous VO, mortality and relapse rates are higher; hence, further prevention measures should be assessed. PMID:25621677

  14. Molecular epidemiology, antimicrobial susceptibilities and resistance mechanisms of Streptococcus pyogenes isolates resistant to erythromycin and tetracycline in Spain (19942006)

    PubMed Central

    2012-01-01

    Background Group A Streptococcus (GAS) causes human diseases ranging in severity from uncomplicated pharyngitis to life-threatening necrotizing fasciitis and shows high rates of macrolide resistance in several countries. Our goal is to identify antimicrobial resistance in Spanish GAS isolates collected between 1994 and 2006 and to determine the molecular epidemiology (emm/T typing and PFGE) and resistance mechanisms of those resistant to erythromycin and tetracycline. Results Two hundred ninety-five out of 898 isolates (32.8%) were erythromycin resistant, with the predominance of emm4T4, emm75T25, and emm28T28, accounting the 67.1% of the 21 emm/T types. Spread of emm4T4, emm75T25 and emm28T28 resistant clones caused high rates of macrolide resistance. The distribution of the phenotypes was M (76.9%), cMLSB (20.3%), iMLSB (2.7%) with the involvement of the erythromycin resistance genes mef(A) (89.5%), msr(D) (81.7%), erm(B) (37.3%) and erm(A) (35.9%). Sixty-one isolates were tetracycline resistant, with the main representation of the emm77T28 among 20 emm/T types. To note, the combination of tet(M) and tet(O) tetracycline resistance genes were similar to tet(M) alone reaching values close to 40%. Resistance to both antibiotics was detected in 19 isolates of 7 emm/T types, being emm11T11 and the cMLSB phenotype the most frequent ones. erm(B) and tet(M) were present in almost all the strains, while erm(A), mef(A), msr(D) and tet(O) appeared in less than half of them. Conclusions Spanish GAS were highly resistant to macrolides meanwhile showed minor resistance rate to tetracycline. A remarkable correlation between antimicrobial resistance and emm/T type was noticed. Clonal spread of emm4T4, emm75T25 and emm28T28 was the main responsable for macrolide resistance where as that emm77T28 clones were it to tetraclycline resistance. A wide variety of macrolide resistance genes were responsible for three macrolide resistance phenotypes. PMID:22998619

  15. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.

    PubMed

    Hathaway, Lucy J; Grandgirard, Denis; Valente, Luca G; Täuber, Martin G; Leib, Stephen L

    2016-03-01

    Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  16. Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease

    PubMed Central

    Chao, Yashuan; Marks, Laura R.; Pettigrew, Melinda M.; Hakansson, Anders P.

    2015-01-01

    Streptococcus pneumoniae (the pneumococcus) is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over one million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo. In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of pneumococcal biofilm formation and dispersion will elucidate novel avenues to interfere with the spread of antibiotic resistance and vaccine escape, as well as novel strategies to target the mechanisms involved in induction of pneumococcal disease. PMID:25629011

  17. StreptInCor: A Candidate Vaccine Epitope against S. pyogenes Infections Induces Protection in Outbred Mice

    PubMed Central

    Postol, Edilberto; Alencar, Raquel; Higa, Fabio T.; Freschi de Barros, Samar; Demarchi, Lea M. F.; Kalil, Jorge; Guilherme, Luiza

    2013-01-01

    Infection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections. PMID:23593359

  18. Genome Sequence of Streptococcus parauberis Strain KCTC11980, Isolated from Diseased Paralichthys olivaceus

    PubMed Central

    Park, Myoung Ae; Kwon, Mun Gyeong; Hwang, Jee Youn; Jung, Sung Hee; Kim, Dong-Wook; Park, Jin-Young; Kim, Ji-Sun; Na, Yun-Jeong; Kim, Min-Young; Kim, Dae-Soo

    2013-01-01

    Streptococcus parauberis is a coccoid, nonmotile, alpha-hemolytic, Gram-positive bacterium of the Streptococcaceae family. Streptococcus parauberis strain KCTC11980 was isolated from the kidney of a diseased olive flounder collected from an aquaculture farm on Jeju Island in 2010. The 2.12-Mb genome sequence consists of 44 large contigs in 16 scaffolds and contains 2,214 predicted protein-coding genes, with a G+C content of 35.4%. PMID:24092782

  19. Spontaneous fistulisation and drainage of a pyogenic liver abscess into the stomach in an adult patient with sickle cell disease.

    PubMed

    Islam, Shariful; Hosein, Devin; Bheem, Vinoo; Harnarayan, Patrick

    2016-01-01

    Spontaneous endoluminal drainage of a pyogenic liver abscess is a rare phenomenon. Similarly, there are only a few cases in the English literature describing hepatic abscesses as an unusual complication of sickle cell anaemia. Having these two phenomena occurring in the same patient is truly a rarity. We describe a case of a 45-year-old man with homozygous sickle cell anaemia who presented to our institution with a pyogenic liver abscess. He had spontaneous drainage of the abscess after spontaneous fistulisation, with the stomach obviating the need for percutaneous drainage. PMID:26976835

  20. Complete genome sequence of a virulent Streptococcus agalactiae strain 138P isolated from diseased Nile tilapia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus agalactiae strain 138P was isolated from the kidney of diseased Nile tilapia in Idaho during a 2007 streptococcal disease outbreak. The full genome of S. agalactiae 138P is 1,838,716 bp. The availability of this genome will allow comparative genomics to identify genes for antigen disco...

  1. Pyogenic psoas abscess: analysis of 27 cases.

    PubMed

    Lin, M F; Lau, Y J; Hu, B S; Shi, Z Y; Lin, Y H

    1999-12-01

    From 1993 to 1998, 29 pyogenic psoas abscesses occurring in 27 patients were seen in Taichung Veterans General Hospital. Their age range was 25 to 85 years. Diabetes mellitus was the leading underlying disease. Fever and pain in the flank area, back and hip were the usual manifestations. The duration of symptoms prior to the diagnosis ranged from 3 days to 6 months. Most abscesses were diagnosed by computed tomography (CT) images and proven by abscess cultures, which were divided into primary and secondary types. Eighteen of 29 abscesses were regarded as primary. Staphylococcus aureus was the most common pathogen in the primary abscesses, followed by Streptococcus agalactiae, Escherichia coli, viridans streptococci, S. epidermidis, and Salmonella spp.. In the secondary abscess category, E. coli was the leading organism in this series, followed by S. aureus, Klebsiella pneumoniae, viridans streptococci and Candida albicans. The associated conditions included epidural abscess, osteomyelitis, septic arthritis, perirenal abscess, pulmonary tuberculosis, empyema, hydronephrosis and trauma history. The initial empiric therapy comprised mostly of cefazolin or oxacillin with or without an aminoglycoside. Thirteen patients underwent percutaneous drainage, while six received surgical debridement, including two with a recurrent abscess. One patient had both drainage and debridement. Others received medical treatment only. Two of the patients with primary abscess died in spite of percutaneous drainage. Therefore, open drainage, besides appropriate antibiotic treatment, is still required to control complex abscesses with sepsis. PMID:10650491

  2. Complete Genome Sequence of a Virulent Strain, Streptococcus iniae ISET0901, Isolated from Diseased Tilapia

    PubMed Central

    Zhang, Dunhua; Zhang, Lee

    2014-01-01

    Streptococcus iniae ISET0901 is a virulent strain isolated in 2007 from diseased tilapia. Its full genome is 2,070,856bp. The availability of this genome will allow comparative genomics to identify virulence genes important for the pathogenesis of streptococcosis caused by S.iniae, as well as possible immunogens for vaccine development. PMID:24903878

  3. Association between virulence factors of Escherichia coli, Fusobacterium necrophorum, and Arcanobacterium pyogenes and uterine diseases of dairy cows.

    PubMed

    Bicalho, M L S; Machado, V S; Oikonomou, G; Gilbert, R O; Bicalho, R C

    2012-05-25

    The objective of this study was to evaluate the relationship between bacterial species-specific virulence factors (VFs) present in the uterus at 3 different stages of lactation (1-3, 8-10, and 34-36 days in milk (DIM)) and the incidence of metritis and clinical endometritis in dairy cows. The following VF genes were investigated: plo (pyolysin), cbpA (collagen-binding protein), and fimA (fimbriae expression) which are Arcanobacterium pyogenes specific; fimH (a type 1 pilus component), Escherichia coli specific; and lktA (leukotoxin), Fusobacterium necrophorum specific. Uterine swabs were collected from 111 postpartum dairy cows. PCR was used to detect the presence of plo, cbpA, fimA, fimH, and lktA genes. A. pyogenes cbpA was detected in only 5 samples and therefore was not subjected to further analysis. E. coli (fimH) was significantly associated with metritis and endometritis when detected at 1-3 DIM; F. necrophorum (lktA) was significantly associated with metritis when detected at 1-3 and 8-12 DIM and with endometritis when detected at 34-36 DIM; and A. pyogenes (fimA and plo) was associated with metritis (fimA) when detected at 1-3 DIM and endometritis (fimA and plo) when detected at 8-10 and 34-36 DIM. PMID:22186615

  4. Disseminated emm Type 12 Group A Streptococcus and Review of Invasive Disease.

    PubMed

    Heeke, Arielle L; Blumberg, Henry M; Perry, Jason M; Weiss, David S; Crispell, Emily K; Satola, Sarah W; Salinas, Jorge L

    2015-11-01

    The authors present a case of invasive group A Streptococcus (GAS) in a previously healthy 63-year-old male complicated by trans-esophageal echocardiogram negative endocarditis, septic arthritis, and multiple cerebral septic emboli. Despite antibiotics and drainage of his largest brain abscess, the patient expired. This case highlights the potential mortality from invasive GAS disease. Included is a review of current literature regarding invasive GAS that addresses its presentation, prevalence, virulence and treatment. PMID:25723882

  5. Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis

    PubMed Central

    Weinert, Lucy A.; Chaudhuri, Roy R.; Wang, Jinhong; Peters, Sarah E.; Corander, Jukka; Jombart, Thibaut; Baig, Abiyad; Howell, Kate J.; Vehkala, Minna; Välimäki, Niko; Harris, David; Chieu, Tran Thi Bich; Van Vinh Chau, Nguyen; Campbell, James; Schultsz, Constance; Parkhill, Julian; Bentley, Stephen D.; Langford, Paul R.; Rycroft, Andrew N.; Wren, Brendan W.; Farrar, Jeremy; Baker, Stephen; Hoa, Ngo Thi; Holden, Matthew T.G.; Tucker, Alexander W.; Maskell, Duncan J.; Bossé, Janine T.; Li, Yanwen; Maglennon, Gareth A.; Matthews, Dominic; Cuccui, Jon; Terra, Vanessa

    2015-01-01

    Streptococcus suis causes disease in pigs worldwide and is increasingly implicated in zoonotic disease in East and South-East Asia. To understand the genetic basis of disease in S. suis, we study the genomes of 375 isolates with detailed clinical phenotypes from pigs and humans from the United Kingdom and Vietnam. Here, we show that isolates associated with disease contain substantially fewer genes than non-clinical isolates, but are more likely to encode virulence factors. Human disease isolates are limited to a single-virulent population, originating in the 1920, s when pig production was intensified, but no consistent genomic differences between pig and human isolates are observed. There is little geographical clustering of different S. suis subpopulations, and the bacterium undergoes high rates of recombination, implying that an increase in virulence anywhere in the world could have a global impact over a short timescale. PMID:25824154

  6. Nonoutbreak Surveillance of Group A Streptococci Causing Invasive Disease in Portugal Identified Internationally Disseminated Clones among Members of a Genetically Heterogeneous Population▿

    PubMed Central

    Friães, A.; Ramirez, M.; Melo-Cristino, J.

    2007-01-01

    The typing of 160 invasive Streptococcus pyogenes isolates confirmed the importance of pulsed-field gel electrophoresis and multilocus sequence typing for defining clones. The results identified an extremely diverse population and highlighted the importance of both internationally disseminated and local clones not previously associated with invasive disease. PMID:17460058

  7. Safety and efficacy of vaccination against streptococcus pneumonia in patients with rheumatic diseases.

    PubMed

    Elkayam, Ori; Ablin, Jacob; Caspi, Dan

    2007-04-01

    Vaccination against streptococcus pneumonia is currently recommended for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Safety and efficacy issues of vaccination in patients suffering from rheumatic diseases are still unresolved. This review summarizes the studies performed on the safety and immunogenicity of pneumococcal vaccination in patients with RA and SLE, with special emphasis on the effect of immunosuppressive drugs on the efficacy of the vaccine. Several trials have shown that the vaccine does not induce clinical exacerbation of RA and that it does induce an adequate humoral response, albeit one lower than that in healthy controls. PMID:17412304

  8. Pyogenic abscess (image)

    MedlinePLUS

    ... become infected. The most common infecting bacteria include E. coli, Enterococcus, Staphylococcus and Streptococcus. Treatment is usually a combination of drainage and prolonged antibiotic therapy.

  9. Draft Genome Sequence of Trueperella pyogenes, Isolated from the Infected Uterus of a Postpartum Cow with Metritis

    PubMed Central

    Goldstone, Robert J.; Amos, Matt; Talbot, Richard; Schuberth, Hans-Joachim; Sandra, Olivier; Sheldon, I. Martin

    2014-01-01

    Trueperella pyogenes is a common commensal bacterium and an opportunistic pathogen associated with chronic purulent disease, particularly in ruminants. We report here the genome sequence of a T. pyogenes isolate from a severe case of bovine metritis. This is the first full record of a T. pyogenes genome. PMID:24762932

  10. Evaluation of Salivary Streptococcus mutans and Dental Caries in Children with Heart Diseases

    PubMed Central

    Ajami, Behjatolmolook; Abolfathi, Ghazale; Mahmoudi, Eftekhar; Mohammadzadeh, Zahra

    2015-01-01

    Background and aims. In the presence of certain systemic diseases, oral microflora may aggravate the condition of the disease. Microbial population in the oral cavity especially with heart disease can increase the risk of bacterial endocarditis. The aim of this study was to evaluate the rate of oral Streptococcus mutansand the rate of caries in children suffering from heart disease. Materials and methods. In this cross-sectional research, 66 children with congenital or acquired heart disease and 50 healthy children were selected. Children were orally examined and decayed, missing, and filled teeth (DMFT) index was recorded for each subject. Saliva samples were taken from all subjects, and cultured on a special laboratory media and another specific media for S. mutans (sorbitoll +manitol). Bacterial counts were recorded, and for statistical analysis, chi square, Pearsons, and Exact Fisher tests were performed using SPSS 16 software. Results. The rate of S. mutans in children with congenital heart disease was significantly higher than the rates in childrenwith acquired heart disease and healthy control subjects. The mean DMFT in children with acquired heart disease who tookpenicillin as prophylaxis monthly was significantly lower than the other groups. Conclusion. The results revealed lower oral bacteria counts and comparatively lower caries rates in children with heart diseases, probably because of an effect of the regular prophylactic antibiotic regimen. PMID:26236437

  11. Milleri group streptococcus--a stepchild in the viridans family.

    PubMed

    Siegman-Igra, Y; Azmon, Y; Schwartz, D

    2012-09-01

    The purpose of this investigation was to provide a comprehensive review of the pathogenic role and spectrum of disease of milleri group streptococci, with special attention to bloodstream invasion and to possible differential roles among the three species. All consecutive isolates of milleri group streptococci from any anatomic source, during a 37-month period, in a tertiary care teaching hospital in Tel-Aviv, Israel, were thoroughly investigated. Identification to the species level was performed by an automated system.Streptococcus anginosus constituted 82% of the 245 patient-unique isolates from hospitalized patients. All nonurinary isolates were involved in pyogenic infections mostly originating from the gastrointestinal tract, with bacteremia in 28 cases. The 71 urinary isolates represented either urinary tract infection or nonsignificant bacteriuria. No specific association could be detected between species and the infection site, except for a higher relative representation of Streptococcus constellatus in bacteremia. Milleri group streptococci are common in clinical practice and play a different pathogenic role to other viridans streptococci. Due to their invariable association with pyogenic processes, their presence in blood warrants immediate focus identification. In addition, they have a previously unappreciated clinical niche concerning urinary tract infection. The identification of viridans streptococci to the species level is of paramount clinical significance. PMID:22391759

  12. Remission of minimal change disease in Type 2 diabetes after streptococcus bacteremia.

    PubMed

    Enriquez, R; Sirvent, A E; Padilla, S; Andrada, E; Amors, F; Fernandez-Lozano, J A; Gutirrez, F

    2009-02-01

    A 41-year-old man with Type 2 diabetes developed sudden onset of nephrotic syndrome. He initially refused a renal biopsy. However, 3 months later, the nephrotic syndrome persisted and percutaneous renal biopsy was performed. The study with light microscopy, immunofluorescence and electron microscopy showed minimal change disease. Three weeks after biopsy, before immunosuppressive therapy was begun, the patient presented Group A Streptococcus (GAS) bacteremia and acute renal failure which needed hemodialysis. Afterwards, the renal function recovered and complete remission of the nephrotic syndrome, maintained during a 22-month follow-up, was observed. We discuss the possible mechanisms implicated in the remission. This report extends the spectrum of infections associated with remission of minimal change disease (MCD). PMID:19203511

  13. Clonal distribution of Streptococcus suis isolated from diseased pigs in the central region of Chile.

    PubMed

    Morales, Brbara; Ruiz, lvaro; Lacouture, Sonia; Gottschalk, Marcelo

    2015-10-01

    The characteristics of 29 Chilean field strains of Streptococcus suis recovered between 2007 and 2011 from pigs with clinical signs at different farms were studied. Serotyping with use of the coagglutination test revealed that all but 1 strain belonged to serotype 6; the remaining strain was serotype 22. All the serotype-6 strains were suilysin (hemolysin)-negative; in addition, they were found to be genotypically homogeneous by enterobacterial repetitive intergenic consensus sequence-based polymerase chain reaction (ERIC-PCR) and sensitive to ampicillin, ceftiofur, penicillin, and trimethoprim/sulfamethoxazole. The results indicate that, in contrast to what is generally observed in other countries, a single clone of S. suis was isolated from diseased pigs in the central region of Chile. PMID:26424917

  14. Streptococcus suis infection: an emerging/reemerging challenge of bacterial infectious diseases?

    PubMed

    Feng, Youjun; Zhang, Huimin; Wu, Zuowei; Wang, Shihua; Cao, Min; Hu, Dan; Wang, Changjun

    2014-05-15

    Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial strains that represents a primary health problem in the swine industry worldwide. S. suis is also an emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis). Over the past few decades, continued efforts have made significant progress toward better understanding this zoonotic infectious entity, contributing in part to the elucidation of the molecular mechanism underlying its high pathogenicity. This review is aimed at presenting an updated overview of this pathogen from the perspective of molecular epidemiology, clinical diagnosis and typing, virulence mechanism, and protective antigens contributing to its zoonosis. PMID:24667807

  15. Multiple Subungual Pyogenic Granulomas Following Levothyroxine Treatment.

    PubMed

    Keles, Musa Kemal; Yosma, Engin; Aydogdu, Ilhami Oguzhan; Simsek, Tekin; Park, Tae Hwan

    2015-09-01

    Pyogenic granulomas are benign vascular lesions that can result from a large number of etiological factors. Drugs are one etiological factor involved in pyogenic granuloma development. In this study we present our experience of multiple pyogenic granulomas following levothyroxine administration suggesting that levothyroxine hormone replacement therapy might play an important role in the formation of pyogenic granuloma. We also reviewed the literatures regarding drug-induced pyogenic granulomas. PMID:26355986

  16. Pneumolysin Expression by Streptococcus pneumoniae Protects Colonized Mice from Influenza Virus-induced Disease

    PubMed Central

    Wolf, Amaya I.; Strauman, Maura C.; Mozdzanowska, Krystyna; Williams, Katie L.; Osborne, Lisa C.; Shen, Hao; Liu, Qin; Garlick, David; Artis, David; Hensley, Scott E.; Caton, Andrew J.; Weiser, Jeffrey N.; Erikson, Jan

    2014-01-01

    The response to influenza virus (IAV) infection and severity of disease is highly variable in humans. We hypothesized that one factor contributing to this variability is the presence of specific respiratory tract (RT) microbes. One such microbe is Streptococcus pneumoniae (Sp) that is carried asymptomatically in the RT of many humans. In a mouse co-infection model we found that in contrast to secondary bacterial infection that exacerbates disease, Sp colonization 10 days prior to IAV protects from virus-induced morbidity and lung pathology. Using mutant Sp strains, we identified a critical role for the bacterial virulence factor pneumolysin (PLY) in mediating this protection. Colonization with the PLY-sufficient Sp strain induces expression of the immune-suppressive enzyme arginase 1 in alveolar macrophages (aM) and correlates with attenuated recruitment and function of pulmonary inflammatory cells. Our study demonstrates a novel role for PLY in Sp-mediated protection by maintaining aM as "gatekeepers" against virus-induced immunopathology. PMID:24999050

  17. Evidence of lateral gene transfer among strains of Streptococcus zooepidemicus in weanling horses with respiratory disease.

    PubMed

    Velineni, Sridhar; Breathnach, Cormac C; Timoney, John F

    2014-01-01

    Streptococcus zooepidemicus (Sz) is a tonsillar commensal of healthy horses but with potential to opportunistically invade the lower respiratory tract. Sz is genetically variable and recombinogenic based on analysis of gene sequences including szp, szm and MLST data. Although a variety of serovars of the protective SzP are commonly harbored in the tonsils of the same horse, lower respiratory infections usually involve a single clone. Nevertheless, isolation of specific clones from epizootics of respiratory disease has been recently reported in horses and dogs in N. America, Europe and Asia. In this report, we provide evidence suggestive of lateral gene exchange and recombination between strains of Sz from cases of respiratory disease secondary to experimental equine herpes 1 virus infection in an isolated group of weanling horses and ponies. Nasal swabs of 13 of 18 weanlings with respiratory disease yielded mucoid colonies of Sz following culture. Comparison of arcC, nrdE, proS, spi, tdk, tpi and yqiL of these Sz revealed 3 Clades. Clade-1 (ST-212) and 2 (ST-24) were composed of 7 and 3 isolates, respectively. ST-24 and 212 differed in all 7 housekeeping as well as szp and szm alleles. Two isolates of Clade-1 were assigned to ST-308, a single locus variant of ST-212 that contained the proS-16 allele sequenced in ST-24. One isolate of ST-308 contained szm-2, the same allele sequenced in Clade 2 isolates; the other was positive for the szp-N2HV2 allele of Clade 2. These observations are consistent with gene transfer between Sz in the natural host and may explain formation of novel clones that invade the lower respiratory tract or cause epizootics of respiratory disease in dogs and horses. PMID:24263112

  18. Weekly Teriparatide Therapy Rapidly Accelerates Bone Healing in Pyogenic Spondylitis with Severe Osteoporosis

    PubMed Central

    Ueno, Yutaka; Marumo, Keishi

    2014-01-01

    Pyogenic spondylitis is a frequently observed disease in orthopedics, and the number of cases is increasing. Some patients with pyogenic spondylitis suffer from vertebral destruction due to infection. The disease is typically treated with antibiotics, bed rest, spinal support, and lesion curettage; however, vigorous drug therapy against vertebral body destruction by pyogenic spondylitis has not been attempted. In this report, a case of pyogenic spondylitis with spinal destruction caused by infection and treated with once-weekly teriparatide administration is presented. Vertebral body erosion in cortical and cancellous areas by the infection was rapidly repaired after 6 weeks of once-weekly teriparatide treatment. Treatment with once-weekly teriparatide appears to be a new strategy for patients with severe osteoporosis suffering from pyogenic spondylitis. PMID:25187868

  19. IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pichavant, Muriel; Sharan, Riti; Le Rouzic, Olivier; Olivier, Ccile; Hennegrave, Florence; Rmy, Galle; Prez-Cruz, Magdiel; Kon, Bachirou; Gosset, Pierre; Just, Nicolas; Gosset, Philippe

    2015-01-01

    Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1? and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1? and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation. PMID:26870795

  20. Neonatal Streptococcus pneumoniae Infection May Aggravate Adulthood Allergic Airways Disease in Association with IL-17A

    PubMed Central

    Yang, Ting; Jiang, Xiaoli; Zhang, Liqun; Wang, Lijia; Wang, Qinghong; Luo, Zhengxiu; Liu, Enmei; Fu, Zhou

    2015-01-01

    Epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. However, little is known about the mechanisms by which early-life bacterial infection increases this risk. The aim of this study was to investigate the effect of neonatal Streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. A non-lethal S. pneumoniae lung infection was established by intranasal inoculation of neonatal (1-week-old) female mice with D39. Mice were sensitized and challenged with ovalbumin in adulthood to induce allergic airways disease (AAD). Twenty-four hours later, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. Neonatal S. pneumoniae infection exacerbated adulthood hallmark features of AAD, with enhanced airway hyperresponsiveness and increased neutrophil recruitment into the airways, increased Th17 cells and interleukin (IL)-17A productions. Depletion of IL-17A by i.p. injection of a neutralizing monoclonal antibody reduced neutrophil recruitment into the airways, alleviated airway inflammation and decreased airway hyperresponsiveness. Furthermore, IL-17A depletion partially restored levels of inteferon-?, but had no effect on the release of IL-5 or IL-13. Our data suggest that neonatal S. pneumoniae infection may promote the development of adulthood asthma in association with increased IL-17A production. PMID:25816135

  1. Molecular epidemiology of Streptococcus zooepidemicus infection in naturally occurring equine respiratory disease.

    PubMed

    Newton, J R; Laxton, R; Wood, J L N; Chanter, N

    2008-03-01

    The objective of the study was to characterise the molecular epidemiology of Streptococcus zooepidemicus infection among isolates collected sequentially from recently weaned, pasture maintained Welsh mountain ponies with naturally occurring respiratory disease. Weekly nasopharyngeal and tracheal lavage samplings over a 10-week period were conducted in 29 ponies. Two PCR typing methods based on characterisation of the M-protein hypervariable (HV) region and the 16S-23S rRNA gene intergenic spacer were then applied to isolates of S. zooepidemicus recovered from nasopharyngeal swab and tracheal wash samples. S. zooepidemicus infection was highly prevalent during the study, being isolated from 94% of tracheal washes and 88% of nasopharyngeal swabs. Among 39 different S. zooepidemicus types isolated, more were isolated from the trachea (n=33) than the nasopharynx (n=27). There was evidence from temporal patterns of infection for clonal succession over time by the more prevalent S. zooepidemicus types. Novel S. zooepidemicus types were identified, including previously untyped HV regions and intra-strain multiples of both the HV region and intergenic spacer types. PMID:17433734

  2. Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease.

    PubMed

    Landwehr-Kenzel, Sybille; Henneke, Philipp

    2014-01-01

    Streptococcus agalactiae (Group B streptococcus, GBS) is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis, and death at the beginning of life, in the elderly and in diabetic patients. Thus, GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days 7 and 90 of life are at risk of a particularly striking sepsis manifestation (late-onset disease), where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases are caused by one clone, GBS ST17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood-brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels, and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like glycerinaldehyde-3-phosphate-dehydrogenase-dependent induction of IL-10 and β-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are just emerging. PMID:25400631

  3. Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

    PubMed Central

    Landwehr-Kenzel, Sybille; Henneke, Philipp

    2014-01-01

    Streptococcus agalactiae (Group B streptococcus, GBS) is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis, and death at the beginning of life, in the elderly and in diabetic patients. Thus, GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days 7 and 90 of life are at risk of a particularly striking sepsis manifestation (late-onset disease), where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases are caused by one clone, GBS ST17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood–brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels, and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like glycerinaldehyde-3-phosphate-dehydrogenase-dependent induction of IL-10 and β-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are just emerging. PMID:25400631

  4. Streptococcus dysgalactiae subsp. equisimilis bacteremia: an emerging infection.

    PubMed

    Rantala, S

    2014-08-01

    The importance of group C and G Streptococcus dysgalactiae subspecies equisimilis (S. dysgalactiae subsp. equisimilis) as a significant pathogen has recently been better recognized. S. dysgalactiae subsp. equisimilis disease can range in severity from milder skin and soft-tissue conditions such as wound infection, erysipelas, and cellulitis, to life-threatening necrotizing fasciitis and streptococcal toxic shock syndrome, thus sharing the clinical picture with S. pyogenes. The most common clinical manifestation of bacteremia is cellulitis. An increase in the incidence of S. dysgalactiae subsp. equisimilis bacteremia has been recognized. Invasive forms of this infection are most commonly found in elderly patients with underlying comorbidities and skin breakdown. The case fatality in bacteremia has been reported to be 15-18%. In this review, the epidemiology, clinical characteristics, and emm types of S. dysgalactiae subsp. equisimilis bacteremia are summarized. PMID:24682845

  5. Antimicrobial Effect of Lactobacillus reuteri on Cariogenic Bacteria Streptococcus gordonii, Streptococcus mutans, and Periodontal Diseases Actinomyces naeslundii and Tannerella forsythia.

    PubMed

    Baca-Castañón, Magda Lorena; De la Garza-Ramos, Myriam Angélica; Alcázar-Pizaña, Andrea Guadalupe; Grondin, Yohann; Coronado-Mendoza, Anahí; Sánchez-Najera, Rosa Isela; Cárdenas-Estrada, Eloy; Medina-De la Garza, Carlos Eduardo; Escamilla-García, Erandi

    2015-03-01

    Lactic acid bacteria (LAB) are well known for their beneficial effects on human health in the intestine and immune system; however, there are few studies on the impact they can generate in oral health. The aim of this study was to test and compare in vitro antimicrobial activity of L. reuteri on pathogenic bacteria involved in the formation of dental caries: S. mutans, S. gordonii, and periodontal disease: A. naeslundii and T. forsythia. Also, we determined the growth kinetics of each bacterium involved in this study. Before determining the antimicrobial action of L. reuteri on cariogenic bacteria and periodontal disease, the behavior and cell development time of each pathogenic bacterium were studied. Once the conditions for good cell growth of each of selected pathogens were established according to their metabolic requirements, maximum exponential growth was determined, this being the reference point for analyzing the development or inhibition by LAB using the Kirby Bauer method. Chlorhexidine 0.12% was positive control. L. reuteri was shown to have an inhibitory effect against S. mutans, followed by T. forsythia and S. gordonii, and a less significant effect against A. naeslundii. Regarding the effect shown by L. reuteri on the two major pathogens, we consider its potential use as a possible functional food in the prevention or treatment of oral diseases. PMID:25422124

  6. Arcanobacterium pyogenes endocarditis: a case report and literature review.

    PubMed

    Chesdachai, Supavit; Larbcharoensub, Noppadol; Chansoon, Tharintorn; Chalermsanyakorn, Panas; Santanirand, Pitak; Chotiprasitsakul, Darunee; Ratanakorn, Disya; Boonbaichaiyapruck, Sarana

    2014-01-01

    We report the case of a 64-year-old man with Arcanobacterium pyogenes endocarditis. The patient presented with dyspnea and asymmetrical progressive quadriparesis. A transthoracic echocardiogram revealed mobile vegetations on both leaflets of his mitral valve measuring 0.5 x 3 cm, thickening of the mitral valve with severe mitral regurgitation due to dehiscence of the papillary muscle to the posterior mitral leaflet. He also had aortic sclerosis with a vegetation measuring 0.5 x 1 cm causing aortic valve dehiscence and free flow aortic regurgitation. An initial hemoculture grew out pleomorphic, gram-positive, non-motile, anaerobic to microaerophilic bacilli. A diagnosis of infective endocarditis was made using modified Duke criteria. He was treated with intravenous ampicillin and gentamicin. Four days after admission, he developed acute respiratory failure and succumbed to the disease. A pre-mortem hemoculture and post-mortem heart valve culture grew Arcanobacterium pyogenes. Septic thromboemboli involving the brain, kidneys, lungs and spleen were documented. The patient also had ischemic vasculopathy with focal spinal arteriolitis and bilateral demyelination of the cervical corticospinal tracts. There are three published reports of human A. pyogenes endocarditis in the literature. Neurological involvement with ischemic spinal vasculopathy and demyelination has not been reported. We report the first autopsy proven case of A. pyogenes infective endocarditis with ischemic spinal vasculopathy. We review the clinicopathologic features of systemic A. pyogenes infection. PMID:24964663

  7. Genome Anatomy of Streptococcus parasanguinis Strain C1A, Isolated from a Patient with Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Reveals Unusual Genomic Features

    PubMed Central

    Ng, Kim Tien; Pang, Yong Kek; Chong, Teik Min; Kamarulzaman, Adeeba; Yin, Wai-Fong; Tee, Kok Keng

    2015-01-01

    Streptococcus parasanguinis causes invasive diseases. However, the mechanism by which it causes disease remains unclear. Here, we describe the complete genome sequence of S.parasanguinis C1A, isolated from a patient diagnosed with an acute exacerbation of chronic obstructive pulmonary disease. Several genes that might be associated with pathogenesis are also described. PMID:26021924

  8. Burden of Invasive Group B Streptococcus Disease and Early Neurological Sequelae in South African Infants

    PubMed Central

    Dangor, Ziyaad; Lala, Sanjay G.; Cutland, Clare L.; Koen, Anthonet; Jose, Lisa; Nakwa, Firdose; Ramdin, Tanusha; Fredericks, Joy; Wadula, Jeannette; Madhi, Shabir A.

    2015-01-01

    Introduction Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (06 days of life, EOD) and late-onset (789 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. Methods A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. Results We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.249.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.4449.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.1710.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44120.95) greater in cases (13.2%) than controls (0.4%). Discussion The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting. PMID:25849416

  9. Direct Host Plasminogen Binding to Bacterial Surface M-protein in Pattern D Strains of Streptococcus pyogenes Is Required for Activation by Its Natural Coinherited SK2b Protein.

    PubMed

    Chandrahas, Vishwanatha; Glinton, Kristofor; Liang, Zhong; Donahue, Deborah L; Ploplis, Victoria A; Castellino, Francis J

    2015-07-24

    Streptokinase (SK), secreted by Group A Streptococcus (GAS), is a single-chain ∼47-kDa protein containing three consecutive primary sequence regions that comprise its α, β, and γ modules. Phylogenetic analyses of the variable β-domain sequences from different GAS strains suggest that SKs can be arranged into two clusters, SK1 and SK2, with a subdivision of SK2 into SK2a and SK2b. SK2b is secreted by skin-tropic Pattern D M-protein strains that also express plasminogen (human Pg (hPg)) binding Group A streptococcal M-protein (PAM) as its major cell surface M-protein. SK2a-expressing strains are associated with nasopharynx tropicity, and many of these strains express human fibrinogen (hFg) binding Pattern A-C M-proteins, e.g. M1. PAM interacts with hPg directly, whereas M1 binds to hPg indirectly via M1-bound hFg. Subsequently, SK is secreted by GAS and activates hPg to plasmin (hPm), thus generating a proteolytic surface on GAS that enhances its dissemination. Due to these different modes of hPg/hPm recognition by GAS, full characterizations of the mechanisms of activation of hPg by SK2a and SK2b and their roles in GAS virulence are important topics. To more fully examine these subjects, isogenic chimeric SK- and M-protein-containing GAS strains were generated, and the virulence of these chimeric strains were analyzed in mice. We show that SK and M-protein alterations influenced the virulence of GAS and were associated with the different natures of hPg activation and hPm binding. These studies demonstrate that GAS virulence can be explained by disparate hPg activation by SK2a and SK2b coupled with the coinherited M-proteins of these strains. PMID:26070561

  10. Properties and antimicrobial susceptibility of Trueperella pyogenes isolated from bovine mastitis in China.

    PubMed

    Alkasir, Rashad; Wang, Jianfang; Gao, Jian; Ali, Tariq; Zhang, Limei; Szenci, Ottó; Bajcsy, Árpád Csaba; Han, Bo

    2016-03-01

    Trueperella (T.) pyogenes is an opportunistic pathogen that causes suppurative diseases in domestic animals. In this work, the properties, pathogenesis and phenotypic diversity of T. pyogenes isolates from bovine mastitis were studied. Both pyolysin (plo) and collagen-binding protein (cbp) virulence factor genes were detected by PCR in all T. pyogenes isolates (n = 50). Using the tissue culture plate method, 90% of T. pyogenes isolates were able to form biofilms. The minimum inhibitory concentrations (MICs) of 13 antimicrobials against T. pyogenes isolates were determined. High susceptibility was observed to rifampin (96%), ampicillin (94%), ciprofloxacin (94%), and penicillin (92%), while low susceptibility was found to trimethoprim-sulphamethoxazole (10%) and bacitracin (2%). The intracellular assay revealed that T. pyogenes isolates had different cytopathogenic effects on cells. The high percentage (28.6%) of T. pyogenes isolates suggests that this bacterium is an important contributor to mastitis. Moreover, the high occurrence of multidrug resistance, biofilm production, intracellular survival, and the temporal dynamics of T. pyogenes interactions are key factors for a better understanding of how immunity acts on infections with these bacteria and how they evade immune surveillance, thus highlighting the need for the prudent use of antimicrobial agents in veterinary medicine. PMID:26919137

  11. Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008-2014.

    PubMed

    Ceyhan, Mehmet; Ozsurekci, Yasemin; Grler, Nezahat; ksz, Ltfiye; Aydemir, Sohret; Ozkan, Sengul; Yuksekkaya, Serife; Keser Emiroglu, Melike; Gltekin, Meral; Yaman, Akgn; Kiremitci, Abdurrahman; Yan?k, Keramettin; Karli, Arzu; Ozcinar, Hatice; Aydin, Faruk; Bayramoglu, Gulcin; Zer, Yasemin; Gulay, Zeynep; Gayyurhan, Efgan Dogan; Gl, Mustafa; zak?n, Cneyt; Gdco?lu, Hseyin; Perin, Duygu; Akpolat, Nezahat; Ozturk, Candan; Camc?o?lu, Y?ld?z; Karada? ncel, Eda; elik, Melda; ?anal, Laser; Uslu, Hakan

    2016-02-01

    Successful vaccination policies for protection from invasive pneumococcal diseases (IPD) dependent on determination of the exact serotype distribution in each country. We aimed to identify serotypes of pneumococcal strains causing IPD in children in Turkey and emphasize the change in the serotypes before and after vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) was included and PCV-13 was newly changed in Turkish National Immunization Program. Streptococcus pneumoniae strains were isolated at 22 different hospitals of Turkey, which provide healthcare services to approximately 65% of the Turkish population. Of the 335 diagnosed cases with S. pneumoniae over the whole period of 2008-2014, the most common vaccine serotypes were 19F (15.8%), 6B (5.9%), 14 (5.9%), and 3 (5.9%). During the first 5y of age, which is the target population for vaccination, the potential serotype coverage ranged from 57.5 % to 36.8%, from 65.0% to 44.7%, and from 77.4% to 60.5% for PCV-7, PCV-10, and PCV-13 in 2008-2014, respectively. The ratio of non-vaccine serotypes was 27.2% in 2008-2010 whereas was 37.6% in 2011-2014 (p=0.045). S. penumoniae serotypes was less non-susceptible to penicillin as compared to our previous results (33.7vs 16.5 %, p=0.001). The reduction of those serotype coverage in years may be attributed to increasing vaccinated children in Turkey and the increasing non-vaccine serotype may be explained by serotype replacement. Our ongoing IPD surveillance is a significant source of information for the decision-making processes on pneumococcal vaccination. PMID:26325175

  12. Interaction between Streptococcus pneumoniae and Staphylococcus aureus in paediatric patients suffering from an underlying chronic disease.

    PubMed

    Esposito, Susanna; Marseglia, Gian Luigi; Colombo, Carla; Iughetti, Lorenzo; Terranova, Leonardo; Ierardi, Valentina; Gambino, Monia; Principi, Nicola

    2015-12-01

    Little is known about the interaction between Streptococcus pneumoniae and Staphylococcus aureus in school-age children and adolescents suffering from an underlying chronic disease. To increase our knowledge in this regard, an oropharyngeal swab was obtained from school-age children and adolescents suffering from asthma (n = 423), cystic fibrosis (CF) (n = 212) and type 1 diabetes mellitus (DM1) (n = 296). S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. Among asthmatic, CF and DM1 patients, both pathogens were identified in 65/423 (15.4%), 21/212 (9.9%) and 62/296 (20.9%) children, respectively; S. pneumoniae alone was identified in 127/434 (30.0%), 21/212 (9.9%) and 86/296 (29.1%), respectively; S. aureus alone was identified in 58/434 (13.7%), 78/212 (36.8%) and 49/296 (16.6%), respectively. S. pneumoniae colonisation rates were higher in younger children and declined with age, whereas the frequency of S. aureus colonisation was quite similar in the different age groups. Among asthmatic and CF patients aged 6-9 years, S. aureus carriage was significantly higher in children who were positive for S. pneumoniae (P <0.05). No significant association emerged between S. aureus carriage and carriage of S. pneumoniae serotypes included in the pneumococcal conjugate vaccines (PCVs). This study shows for the first time that school-age children and adolescents with asthma, CF and DM1 are frequently colonised by S. pneumoniae and S. aureus and that no negative relationship seems to exist between these pathogens. Moreover, the supposed protection offered by PCV administration against S. aureus colonisation was not demonstrated. PMID:26395386

  13. Pyogenic meningitis in Ilesa, Nigeria.

    PubMed

    Ogunlesi, T A; Okeniyi, J A O; Oyelami, O A

    2005-10-01

    This study was conducted in 124 children with meningitis to review the etiology, antimicrobial susceptibility and outcome of disease in a Nigerian tertiary health facility. Of these, 97 (78.27%) were culture positive; in the rest 27(21.8%), diagnosis was based on Gram staining of the CSF. Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus and Escherichia coli were isolated in 33.9%, 33.9%, 5.6%, 2.4%, and 2.4% samples respectively. All the isolates had 100 percent; sensitivity to both ceftriaxone and ciprofloxacin while the sensitivities to penicillin and ampicillin were remarkably low. The mortality was 33/124 (26.6%) while 16/ 91 (17.6%) of the survivors had various neurologic sequelae. PMID:16269839

  14. Review on the association of Group B Streptococcus capsular antibody and protection against invasive disease in infants.

    PubMed

    Dangor, Ziyaad; Kwatra, Gaurav; Izu, Alane; Lala, Sanjay G; Madhi, Shabir A

    2015-01-01

    A trivalent Group B streptococcus (GBS) polysaccharide-protein conjugate vaccine for vaccination of pregnant women is under development to protect their newborns against invasive GBS disease. Establishing sero-correlates of protection against invasive GBS disease in infants could expedite the licensure pathway of polysaccharide-protein conjugate vaccine. A systematic review of studies reporting on the association of capsular antibodies and invasive GBS disease in infants and colonization in women or newborns was undertaken. Most studies that described maternal and/or infant capsular antibody levels in infants with invasive GBS disease identified an association between low capsular antibody levels in invasive GBS cases compared to controls. Different assay methods and the lack of standardized reference ranges for serotype-specific antibody levels makes it difficult to select an antibody level that may be used as a reliable sero-correlate of protection. Further studies using standardized methods are warranted. PMID:25242617

  15. Pyogenic liver abscess: Changing patterns in approach

    PubMed Central

    Malik, Ajaz A; Bari, Shams UL; Rouf, Khawaja Abdul; Wani, Khurshid Alam

    2010-01-01

    AIM: To define optimum management of the pyogenic liver abscess and assess new trends in treatment. METHODS: One hundred and sixty nine patients with pyogenic liver abscess managed at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir (India) from July 2001 to August 2006 were studied to evaluate and define the optimum treatment. RESULTS: Mortality in the surgically treated group of patients was 9.4% (12/119), while those treated non-surgically had a fatality rate of 16.66% (7/42). Multiple liver abscesses treated surgically had a surprisingly low mortality of 30%. The biliary tract (64.97%) was the most common cause of liver abscess. Multiple abscesses, mixed organisms and abscess complications are all associated with a significantly increased mortality. However, the lethality of the primary disease process was the most important factor in determining survival. CONCLUSION: Transperitoneal surgical drainage and antibiotics are the mainstay of treatment. Percutaneous drainage is recommended for high risk patients only. PMID:21206721

  16. Responses of innate immune cells to group A Streptococcus

    PubMed Central

    Fieber, Christina; Kovarik, Pavel

    2014-01-01

    Group A Streptococcus (GAS), also called Streptococcus pyogenes, is a Gram-positive beta-hemolytic human pathogen which causes a wide range of mostly self-limiting but also several life-threatening diseases. Innate immune responses are fundamental for defense against GAS, yet their activation by pattern recognition receptors (PRRs) and GAS-derived pathogen-associated molecular patterns (PAMPs) is incompletely understood. In recent years, the use of animal models together with the powerful tools of human molecular genetics began shedding light onto the molecular mechanisms of innate immune defense against GAS. The signaling adaptor MyD88 was found to play a key role in launching the immune response against GAS in both humans and mice, suggesting that PRRs of the Toll-like receptor (TLR) family are involved in sensing this pathogen. The specific TLRs and their ligands have yet to be identified. Following GAS recognition, induction of cytokines such as TNF and type I interferons (IFNs), leukocyte recruitment, phagocytosis, and the formation of neutrophil extracellular traps (NETs) have been recognized as key events in host defense. A comprehensive knowledge of these mechanisms is needed in order to understand their frequent failure against GAS immune evasion strategies. PMID:25325020

  17. Responses of innate immune cells to group A Streptococcus.

    PubMed

    Fieber, Christina; Kovarik, Pavel

    2014-01-01

    Group A Streptococcus (GAS), also called Streptococcus pyogenes, is a Gram-positive beta-hemolytic human pathogen which causes a wide range of mostly self-limiting but also several life-threatening diseases. Innate immune responses are fundamental for defense against GAS, yet their activation by pattern recognition receptors (PRRs) and GAS-derived pathogen-associated molecular patterns (PAMPs) is incompletely understood. In recent years, the use of animal models together with the powerful tools of human molecular genetics began shedding light onto the molecular mechanisms of innate immune defense against GAS. The signaling adaptor MyD88 was found to play a key role in launching the immune response against GAS in both humans and mice, suggesting that PRRs of the Toll-like receptor (TLR) family are involved in sensing this pathogen. The specific TLRs and their ligands have yet to be identified. Following GAS recognition, induction of cytokines such as TNF and type I interferons (IFNs), leukocyte recruitment, phagocytosis, and the formation of neutrophil extracellular traps (NETs) have been recognized as key events in host defense. A comprehensive knowledge of these mechanisms is needed in order to understand their frequent failure against GAS immune evasion strategies. PMID:25325020

  18. Mechanisms of group A Streptococcus resistance to reactive oxygen species

    PubMed Central

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N.

    2015-01-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the ‘top 10’ causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•−), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  19. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    PubMed

    Henningham, Anna; Dhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2(-)), hydroxyl radicals (OH) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  20. Animal Models Used to Study Superantigen-Mediated Diseases.

    PubMed

    Brosnahan, Amanda J

    2016-01-01

    Superantigens secreted by Staphylococcus aureus and Streptococcus pyogenes interact with the T-cell receptor and major histocompatibility class II molecules on antigen-presenting cells to elicit a massive cytokine release and activation of T cells in higher numbers than that seen with ordinary antigens. Because of this unique ability, superantigens have been implicated as etiological agents for many different types of diseases, including toxic shock syndrome, infective endocarditis, pneumonia, and inflammatory skin diseases. This review covers the main animal models that have been developed in order to identify the roles of superantigens in human disease. PMID:26676033

  1. Streptococcus pyogenes Sternoclavicular Septic Arthritis in a Healthy Adult

    PubMed Central

    Savcic-Kos, Radmila M.; Mali, Padmavati; Abraham, Ajit; Issa, Meltiady; Rangu, Venu; Nasser, Rana

    2014-01-01

    Sternoclavicular septic arthritis is a rare infection, accounting for approximately 1% of septic arthritis in the general population. Staphylococcus aureus is the predominant etiologic agent, and it usually occurs in relatively young adults with some type of predisposition to infection. We report, to the best of our knowledge, the first case of group A streptococcal, sternoclavicular arthritis in a previously healthy 62-year-old male patient. We present a detailed history and physical examination, with laboratory findings, imaging studies, cultures, and therapy. PMID:24667224

  2. Extragingival Pyogenic Granuloma: an Unusual Clinical Presentation.

    PubMed

    Sachdeva, Suresh K

    2015-09-01

    Pyogenic granuloma is thought to represent an exuberant tissue reaction to local irritation. It occurs in second decade of life in young females. Clinically, oral pyogenic granuloma is a smooth or lobulated exophytic growth, pedunculated or sessile, which usually bleeds on provocation. Oral pyogenic granuloma preferentially affects the gingiva. On rare occasion, it can be found extragingivally on lips, tongue, buccal mucosa, and palate which may mimic more serious pathological conditions such as malignancies. This article reports an unusual case of extra gingival pyogenic granuloma occurring on the right buccal mucosa in a female patient and discusses the features that distinguish this lesion from other similar oral mucosal lesions. PMID:26535410

  3. Extragingival Pyogenic Granuloma: an Unusual Clinical Presentation

    PubMed Central

    Sachdeva, Suresh K.

    2015-01-01

    Pyogenic granuloma is thought to represent an exuberant tissue reaction to local irritation. It occurs in second decade of life in young females. Clinically, oral pyogenic granuloma is a smooth or lobulated exophytic growth, pedunculated or sessile, which usually bleeds on provocation. Oral pyogenic granuloma preferentially affects the gingiva. On rare occasion, it can be found extragingivally on lips, tongue, buccal mucosa, and palate which may mimic more serious pathological conditions such as malignancies. This article reports an unusual case of extra gingival pyogenic granuloma occurring on the right buccal mucosa in a female patient and discusses the features that distinguish this lesion from other similar oral mucosal lesions. PMID:26535410

  4. Pyogenic Sacroiliitis in a 13-Month-Old Child

    PubMed Central

    Julien, Leroux; Isabelle, Bernardini; Lucie, Grynberg; Claire, Grandguillaume; Paul, Michelin; Mourad, Ould Slimane; Eric, Nectoux; François, Deroussen; Richard, Gouron; Audrey, Angelliaume; Brice, Ilharreborde; Mariette, Renaux-Petel

    2015-01-01

    Abstract Pyogenic sacroiliitis is exceptional in very young children. Diagnosis is difficult because clinical examination is misleading. FABER test is rarely helpful in very young children. Inflammatory syndrome is frequent. Bone scintigraphy and MRI are very sensitive for the diagnosis. Joint fluid aspiration and blood cultures are useful to identify the pathogen. Appropriate antibiotic therapy provides rapid regression of symptoms and healing. We report the case of pyogenic sacroiliitis in a 13-month-old child. Clinical, biological, and imaging data of this case were reviewed and reported retrospectively. A 13-month-old girl consulted for decreased weight bearing without fever or trauma. Clinical examination was not helpful. There was an inflammatory syndrome. Bone scintigraphy found a sacroiliitis, confirmed on MRI. Aspiration of the sacroiliac joint was performed. Empiric intravenous biantibiotic therapy was started. Patient rapidly recovered full weight bearing. On the 5th day, clinical examination and biological analysis returned to normal. Intravenous antibiotic therapy was switched for oral. One month later, clinical examination and biological analysis were normal and antibiotic therapy was stopped. Hematogenous osteoarticular infections are common in children but pyogenic sacroiliitis is rare and mainly affects older children. Diagnosis can be difficult because clinical examination is poor. Moreover, limping and decreased weight bearing are very common reasons for consultation. This may delay the diagnosis or refer misdiagnosis. Bone scintigraphy is useful to locate a bone or joint disease responsible for limping. In this observation, bone scintigraphy located the infection at the sacroiliac joint. Given the young age, MRI was performed to confirm the diagnosis. Despite the very young age of the patient, symptoms rapidly disappeared with appropriate antibiotic therapy. We report the case of pyogenic sacroiliitis in a 13-month-old child. It reminds the risk of misdiagnosing pyogenic sacroiliitis in children because it is exceptional and clinical examination is rarely helpful. It also highlights the usefulness of bone scintigraphy and MRI in osteoarticular infections in children. PMID:26496260

  5. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    NASA Astrophysics Data System (ADS)

    Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

    2014-11-01

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml-1 with a limit of detection of 0.16 ng ml-1.

  6. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    SciTech Connect

    Singh, Swati; Kumar, Ashok E-mail: ashokigib@rediffmail.com; Khare, Shashi; Mulchandani, Ashok; Rajesh E-mail: ashokigib@rediffmail.com

    2014-11-24

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml{sup −1} with a limit of detection of 0.16 ng ml{sup −1}.

  7. Clonal Complex 17 Group B Streptococcus strains causing invasive disease in neonates and adults originate from the same genetic pool

    PubMed Central

    Teatero, Sarah; Ramoutar, Erin; McGeer, Allison; Li, Aimin; Melano, Roberto G.; Wasserscheid, Jessica; Dewar, Ken; Fittipaldi, Nahuel

    2016-01-01

    A significant proportion of group B Streptococcus (GBS) neonatal disease, particularly late-onset disease, is associated with strains of serotype III, clonal complex (CC) 17. CC17 strains also cause invasive infections in adults. Little is known about the phylogenetic relationships of isolates recovered from neonatal and adult CC17 invasive infections. We performed whole-genome-based phylogenetic analysis of 93 temporally and geographically matched CC17 strains isolated from both neonatal and adult invasive infections in the metropolitan region of Toronto/Peel, Canada. We also mined the whole-genome data to reveal mobile genetic elements carrying antimicrobial resistance genes. We discovered that CC17 GBS strains causing neonatal and adult invasive disease are interspersed and cluster tightly in a phylogenetic tree, signifying that they are derived from the same genetic pool. We identified limited variation due to recombination in the core CC17 genome. We describe that loss of Pilus Island 1 and acquisition of different mobile genetic elements carrying determinants of antimicrobial resistance contribute to CC17 genetic diversity. Acquisition of some of these mobile genetic elements appears to correlate with clonal expansion of the strains that possess them. Our results provide a genome-wide portrait of the population structure and evolution of a major disease-causing clone of an opportunistic pathogen. PMID:26843175

  8. Clonal Complex 17 Group B Streptococcus strains causing invasive disease in neonates and adults originate from the same genetic pool.

    PubMed

    Teatero, Sarah; Ramoutar, Erin; McGeer, Allison; Li, Aimin; Melano, Roberto G; Wasserscheid, Jessica; Dewar, Ken; Fittipaldi, Nahuel

    2016-01-01

    A significant proportion of group B Streptococcus (GBS) neonatal disease, particularly late-onset disease, is associated with strains of serotype III, clonal complex (CC) 17. CC17 strains also cause invasive infections in adults. Little is known about the phylogenetic relationships of isolates recovered from neonatal and adult CC17 invasive infections. We performed whole-genome-based phylogenetic analysis of 93 temporally and geographically matched CC17 strains isolated from both neonatal and adult invasive infections in the metropolitan region of Toronto/Peel, Canada. We also mined the whole-genome data to reveal mobile genetic elements carrying antimicrobial resistance genes. We discovered that CC17 GBS strains causing neonatal and adult invasive disease are interspersed and cluster tightly in a phylogenetic tree, signifying that they are derived from the same genetic pool. We identified limited variation due to recombination in the core CC17 genome. We describe that loss of Pilus Island 1 and acquisition of different mobile genetic elements carrying determinants of antimicrobial resistance contribute to CC17 genetic diversity. Acquisition of some of these mobile genetic elements appears to correlate with clonal expansion of the strains that possess them. Our results provide a genome-wide portrait of the population structure and evolution of a major disease-causing clone of an opportunistic pathogen. PMID:26843175

  9. Huge Pyogenic Granuloma of the Penis

    PubMed Central

    Akbulut, Fatih; Akbulut, Tugba; Kucukdurmaz, Faruk; Sonmezay, Erkan; Simsek, Abdulmuttalip; Gurbuz, Gokhan

    2015-01-01

    Pyogenic granulomas are benign vascular disorders of the skin and mucose membranes, generally developed by trauma and irritation. The lesions are generally small. They are most commonly seen in the skin and oral mucosa and rarely seen on penis. We present the case of a huge pyogenic granuloma on the penis. PMID:26229706

  10. High Incidence of Invasive Group A Streptococcus Disease Caused by Strains of Uncommon emm Types in Thunder Bay, Ontario, Canada.

    PubMed

    Athey, Taryn B T; Teatero, Sarah; Sieswerda, Lee E; Gubbay, Jonathan B; Marchand-Austin, Alex; Li, Aimin; Wasserscheid, Jessica; Dewar, Ken; McGeer, Allison; Williams, David; Fittipaldi, Nahuel

    2016-01-01

    An outbreak of type emm59 invasive group A Streptococcus (iGAS) disease was declared in 2008 in Thunder Bay District, Northwestern Ontario, 2 years after a countrywide emm59 epidemic was recognized in Canada. Despite a declining number of emm59 infections since 2010, numerous cases of iGAS disease continue to be reported in the area. We collected clinical information on all iGAS cases recorded in Thunder Bay District from 2008 to 2013. We also emm typed and sequenced the genomes of all available strains isolated from 2011 to 2013 from iGAS infections and from severe cases of soft tissue infections. We used whole-genome sequencing data to investigate the population structure of GAS strains of the most frequently isolated emm types. We report an increased incidence of iGAS in Thunder Bay compared to the metropolitan area of Toronto/Peel and the province of Ontario. Illicit drug use, alcohol abuse, homelessness, and hepatitis C infection were underlying diseases or conditions that might have predisposed patients to iGAS disease. Most cases were caused by clonal strains of skin or generalist emm types (i.e., emm82, emm87, emm101, emm4, emm83, and emm114) uncommonly seen in other areas of the province. We observed rapid waxing and waning of emm types causing disease and their replacement by other emm types associated with the same tissue tropisms. Thus, iGAS disease in Thunder Bay District predominantly affects a select population of disadvantaged persons and is caused by clonally related strains of a few skin and generalist emm types less commonly associated with iGAS in other areas of Ontario. PMID:26491184

  11. Subtractive genomics approach to identify putative drug targets and identification of drug-like molecules for beta subunit of DNA polymerase III in Streptococcus species.

    PubMed

    Georrge, John J; Umrania, V V

    2012-07-01

    The prolonged use of the antibiotics over the years has transformed many organisms resistant to multiple drugs. This has made the field of drug discovery of vital importance in curing various infections and diseases. The drugs act by binding to a specific target protein of prime importance for the cell's survival. Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes are the few gram positive organisms that have developed resistance to drugs. It causes pneumonia, meningitis, pharyngitis, otitis media, sinusitis, bacteremia, pericarditis, and arthritis infections. The present study was carried out to identify potential drug targets and inhibitors for beta subunit of DNA polymerase III in these three Streptococcus species that might facilitate the discovery of novel drugs in near future. Various steps were adopted to find out novel drug targets. And finally 3D structure of DNA polymerase III subunit beta was modeled. The ligand library was generated from various databases to find the most suitable ligands. All the ligands were docked using Molegro Virtual Docker and the lead molecules were investigated for ADME and toxicity. PMID:22415782

  12. Molecular epidemiology and genomics of group A Streptococcus.

    PubMed

    Bessen, Debra E; McShan, W Michael; Nguyen, Scott V; Shetty, Amol; Agrawal, Sonia; Tettelin, Herv

    2015-07-01

    Streptococcus pyogenes (group A Streptococcus; GAS) is a strict human pathogen with a very high prevalence worldwide. This review highlights the genetic organization of the species and the important ecological considerations that impact its evolution. Recent advances are presented on the topics of molecular epidemiology, population biology, molecular basis for genetic change, genome structure and genetic flux, phylogenomics and closely related streptococcal species, and the long- and short-term evolution of GAS. The application of whole genome sequence data to addressing key biological questions is discussed. PMID:25460818

  13. Microbiology and Management of Pediatric Liver Abscesses: Two Cases Caused by Streptococcus anginosus Group

    PubMed Central

    Cellucci, Michael; Simon, Erin; Eppes, Stephen

    2012-01-01

    Pyogenic liver abscesses in the pediatric population are rare occurrences in the developed world. We present two cases of previously healthy males presenting with fever and abdominal pain found to have liver abscesses due to organisms in the Streptococcus anginosus group. The microbiology of S. anginosus along with the management and recommended treatment in children with liver abscesses is discussed. PMID:23119195

  14. Implications of Streptococcus pneumoniae Penicillin Resistance and Serotype Distribution in Kuwait for Disease Treatment and Prevention?

    PubMed Central

    Mokaddas, Eiman M.; Rotimi, Vincent O.; Albert, M. John

    2008-01-01

    Streptococcus pneumoniae causes serious infections. Treatment is difficult because of the emergence of penicillin resistance in S. pneumoniae. Pneumococcal vaccines offer the promise of control and prevention of pneumococcal infections. Serotype prevalence and penicillin susceptibility data for a country will predict the usefulness of the vaccines in that country. In Kuwait, the 23-valent polysaccharide and the 7-valent conjugate vaccines are being used without knowledge of the prevalent serotypes in the country. To obtain the necessary background information, data on penicillin susceptibility and serogroups were obtained from 397 consecutive clinical isolates collected during 2004 and 2005. Two hundred fifty-three isolates (64%) were penicillin resistant, and resistance was significantly higher in patients ?15 years old and among the upper respiratory tract and eye isolates. The most common serotypes were 23F, 19F, 6A, 6B, 14, and 19A. Among the penicillin-resistant strains, the most common serotypes were 23F, 19F, 6B, 14, and 9A. Among the invasive strains, the most common serotypes were 14, 23F, 19A, and 9V. The polysaccharide vaccine gave 82% coverage against invasive infections in all age groups >2 years. The coverage of the 7-valent conjugate vaccine against invasive serotypes in children ?2 years old was 55%. This moderate coverage by the conjugate vaccine against invasive infections in children necessitates a revised strategy on the use of the present conjugate vaccine and shows the need for formulation of an improved vaccine for superior coverage for Kuwait and possibly other countries of the Arabian Gulf. PMID:18077618

  15. Lack of mitogenic activity of speG- and speG(dys)-positive Streptococcus dysgalactiae subspecies equisimilis isolates from patients with invasive infections.

    PubMed

    Brandt, Claudia M; Schweizer, Klaus G; Holland, Regina; Ltticken, Rudolf; Freyaldenhoven, Bettina S

    2005-12-01

    In recent years, Streptococcus dysgalactiae subspecies equisimilis has been isolated with an increasing frequency as the cause of invasive streptococcal diseases. For 46 S. dysgalactiae subspecies equisimilis isolates from invasive infections and four isolates from superficial infections, the presence of emm/emmL genes and of genes encoding various different streptococcal superantigens was determined by polymerase chain reaction (PCR). Subsequently, PCR products were identified by DNA sequencing, and the expression of mRNA from superantigen genes was assessed by reverse transcriptase-PCR. The mitogenic activity of S. dysgalactiae subspecies equisimilis was assessed by [3H]thymidine incorporation into human lymphocytes and compared with that of Streptococcus agalactiae and Streptococcus pyogenes. All S. dysgalactiae subspecies equisimilis isolates studied harbored an emm/emmL gene. Only in six of the S. dysgalactiae subspecies equisimilis isolates from invasive infections, speG was detected by PCR, two of which were further identified as speGdys by sequencing of the PCR product. None of the S. dysgalactiae subspecies equisimilis isolates harbored any of the genes speA, speB, speC, speF, speH, speI, speJ, speK, speL, speM, smeZ, or ssa of S. pyogenes. In contrast to S. pyogenes, no expression of speG or speGdys mRNA, respectively, was detected in the reverse transcriptase-PCR assay for any of the speG- or speGdys-positive S. dysgalactiae subspecies equisimilis isolates. Moreover, S. dysgalactiae subspecies equisimilis and S. agalactiae revealed no or very low mitogenic activity, while S. pyogenes was a very powerful inducer of proliferative responses. These findings support the hypothesis that the pathogenicity of S. dysgalactiae subspecies equisimilis may be associated in part with the presence of emm/emmL genes, and suggest that the severity of S. dysgalactiae subspecies equisimilis invasive infections is not mediated by superantigen-induced mitogenicity. PMID:16325550

  16. The Core Promoter of the Capsule Operon of Streptococcus pneumoniae Is Necessary for Colonization and Invasive Disease

    PubMed Central

    Shainheit, Mara G.; Mul, Matthew

    2014-01-01

    Streptococcus pneumoniae is a commensal of the human nasopharynx but can cause invasive diseases, including otitis media, pneumonia, sepsis, and meningitis. The capsular polysaccharide (capsule) is a critical virulence factor required for both asymptomatic colonization and invasive disease, yet the expression level is different in each anatomical site. During colonization, reduced levels of capsule promote binding to the host epithelium and biofilm formation, while during systemic infection, increased capsule is required to evade opsonophagocytosis. How this regulation of capsule expression occurs is incompletely understood. To investigate the contribution of transcriptional regulation on capsule level in the serotype 4 strain TIGR4, we constructed two mutants harboring a constitutive promoter that was either comparably weaker (Pcat) or stronger (PtRNAGlu) than the wild-type (WT) capsule promoter, Pcps. Mild reductions in cpsA and cpsE transcript levels in the Pcat promoter mutant resulted in a 2-fold reduction in total amounts of capsule and in avirulence in murine models of lung and blood infection. Additionally, the PtRNAGlu mutant revealed that, despite expressing enhanced levels of cpsA and cpsE and possessing levels of capsule comparable to those of WT TIGR4, it was still significantly attenuated in all tested in vivo niches. Further analysis using chimeric promoter mutants revealed that the WT ?10 and ?35 boxes are required for optimal nasopharyngeal colonization and virulence. These data support the hypothesis that dynamic transcriptional regulation of the capsule operon is required and that the core promoter region plays a central role in fine-tuning levels of capsule to promote colonization and invasive disease. PMID:24478084

  17. Genetic diversity and virulence of novel sequence types of Streptococcus suis from diseased and healthy pigs in China

    PubMed Central

    Wang, Shujie; Gao, Mingming; An, Tongqing; Liu, Yonggang; Jin, Jiamin; Wang, Gang; Jiang, Chenggang; Tu, Yabin; Hu, Shouping; Li, Jinsong; Wang, Jie; Zhou, Dongsheng; Cai, Xuehui

    2015-01-01

    Streptococcus suis is a serious threat to swine industry and public health. In this work, a total of 62 S. suis isolates recovered from infected and healthy pigs from four provinces in northern China were classified by multilocus sequence typing into nine sequence types (STs), including six novel ones, namely, ST417, ST418, ST419, ST420, ST421, and ST422. The majority (64.5%) of these 62 isolates belong to serotype 2; all of these serotype 2 isolates can be assigned into ST1 or ST28 clonal complex, indicating at least two parallel routes of clonal dissemination of these isolates. In these serotype 2 isolates, 23 (20 from healthy pigs and three from diseased pigs) were identified as ST7 strains, which were previously characterized as the cause of streptococcal toxic shock-like syndrome. The novel ST strains lack 89 K pathogenicity island but can cause septicemia and meningitis in a mouse model, showing remarkable differences in virulence. The ST421 strain named HLB causes suppurative encephalitis. Our results highlighted the need for increased surveillance of S. suis in farm-raised pigs in northern China. PMID:25784908

  18. Intramedullary pyogenic abscess in the conus medullaris.

    PubMed

    Hassan, M F; Mohamed, M B; Kalsi, P; Sinar, E J; Bradey, N

    2012-02-01

    Primary pyogenic abscess in the conus medullaris in a healthy adult has never been reported. An urgent MRI scan with contrast and prompt surgical evacuation may lead to good neurological recovery. PMID:22264156

  19. Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview

    PubMed Central

    Rhee, Hanna; Cameron, Daniel J

    2012-01-01

    Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed. PMID:22393303

  20. VACCINES TO PREVENT STREPTOCOCCUS INIAE AND S. AGALACTIAE DISEASE IN TILAPIA OREOCHROMIS NILOTICUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Minimizing the effects of diseases is crucial to prevent mortality, morbidity, and to promote optimal growth and feed conversion in sustained culture of warm-water fish in fresh, estuarine and marine waters. The control of diseases has been dependent on the use of therapeutics since the inception o...

  1. VACCINES TO PREVENT Streptococcus iniae AND S. agalactiae DISEASE IN NILE TILAPIA Oreochromis niloticus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Minimizing the effects of disease is crucial to prevent mortality, morbidity, and to promote optimal growth and feed conversion in sustained culture of warm-water fish in fresh, estuarine and marine waters. The control of diseases has been dependent on the use of therapeutics since the inception of...

  2. Streptococcal toxins: role in pathogenesis and disease.

    PubMed

    Barnett, Timothy C; Cole, Jason N; Rivera-Hernandez, Tania; Henningham, Anna; Paton, James C; Nizet, Victor; Walker, Mark J

    2015-12-01

    Group A Streptococcus (Streptococcus pyogenes), group B Streptococcus (Streptococcus agalactiae) and Streptococcus pneumoniae (pneumococcus) are host-adapted bacterial pathogens among the leading infectious causes of human morbidity and mortality. These microbes and related members of the genus Streptococcus produce an array of toxins that act against human cells or tissues, resulting in impaired immune responses and subversion of host physiological processes to benefit the invading microorganism. This toxin repertoire includes haemolysins, proteases, superantigens and other agents that ultimately enhance colonization and survival within the host and promote dissemination of the pathogen. PMID:26433203

  3. Propionibacterium acnes Pyogenic Liver Abscess and Pylephlebitis

    PubMed Central

    Poursina, Arash; Weissman, Sharon

    2011-01-01

    Reported is an unusual case of pyogenic liver abscess and septic thrombophlebitis of the portal vein in a 44-year-old male caused by Propionibacterium acnes successfully managed with a combination of percutaneous drainage and antimicrobial therapy. To the best of our knowledge, this is the first report of this bacterium isolated in pure culture as the sole etiologic organism of pyogenic liver abscess and pylephlebitis in an adult patient. PMID:25954544

  4. Susceptibility of Arcanobacterium pyogenes from different sources to tetracycline, macrolide and lincosamide antimicrobial agents.

    PubMed

    Trinh, Hien T; Billington, Stephen J; Field, Adam C; Songer, J Glenn; Jost, B Helen

    2002-04-01

    Chlortetracycline, oxytetracycline, and the macrolide, tylosin, are extensively used for growth promotion and disease prophylaxis in the cattle and swine industries in the US. Arcanobacterium pyogenes, a common inhabitant of the mucosal surfaces of cattle and swine, is also a pathogen associated with a variety of infections in these animals. A broth microdilution technique was used to determine the antimicrobial susceptibility of 48 A. pyogenes isolates to macrolides, lincosamides and tetracyclines. The MIC50 and MIC90 for chlortetracycline were 0.12 and 8 mg/l, respectively. Similarly, the MIC50 and MIC90 for oxytetracycline were 0.25 and 8 mg/l, while the MIC50 and MIC90 for tetracycline were 0.25 and 16 mg/l, respectively. The MIC50 and the MIC90 were < or = 0.06 and >64 mg/l, respectively, for erythromycin, tylosin and clindamycin. This resistance pattern indicated that some of these A. pyogenes isolates may carry an MLS(B) resistance determinant. A. pyogenes isolates (12.5%) were resistant to erythromycin, and this percentage doubled when MICs were performed following induction with erythromycin. Of the 48 A. pyogenes isolates, 25 and 41.7% were resistant to MLS(B) antimicrobial agents and the tetracycline derivatives, respectively. MLS(B) resistance was present in 22.2 and 35.3% of A. pyogenes isolates of bovine (n=27) or porcine (n=17) origin. In contrast, 70.6% of porcine isolates were resistant to the tetracyclines, compared with 25.9% of bovine isolates. These data suggest that a large proportion of A. pyogenes field isolates may be resistant to these commonly used antimicrobial agents. PMID:11856585

  5. Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes

    PubMed Central

    Flores, Anthony R.; Galloway-Pea, Jessica; Sahasrabhojane, Pranoti; Saldaa, Miguel; Yao, Hui; Su, Xiaoping; Ajami, Nadim J.; Holder, Michael E.; Petrosino, Joseph F.; Thompson, Erika; Margarit Y Ros, Immaculada; Rosini, Roberto; Grandi, Guido; Horstmann, Nicola; Teatero, Sarah; McGeer, Allison; Fittipaldi, Nahuel; Rappuoli, Rino; Baker, Carol J.; Shelburne, Samuel A.

    2015-01-01

    The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans. PMID:25941374

  6. Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes.

    PubMed

    Flores, Anthony R; Galloway-Peña, Jessica; Sahasrabhojane, Pranoti; Saldaña, Miguel; Yao, Hui; Su, Xiaoping; Ajami, Nadim J; Holder, Michael E; Petrosino, Joseph F; Thompson, Erika; Margarit Y Ros, Immaculada; Rosini, Roberto; Grandi, Guido; Horstmann, Nicola; Teatero, Sarah; McGeer, Allison; Fittipaldi, Nahuel; Rappuoli, Rino; Baker, Carol J; Shelburne, Samuel A

    2015-05-19

    The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans. PMID:25941374

  7. Coaggregation of Streptococcus sanguis and other streptococci with Candida albicans.

    PubMed Central

    Jenkinson, H F; Lala, H C; Shepherd, M G

    1990-01-01

    Thirteen strains of viridans group streptococci and two strains of other streptococci were tested for coaggregation with Candida albicans. Streptococcus sanguis strains generally exhibited low levels of adherence to 28 degrees C-grown exponential-phase yeast cells, but starvation of yeast cells for glucose at 37 degrees C (or at 28 degrees C) increased their coaggregating activity with these streptococci by at least tenfold. This was a property common to four C. albicans strains tested, two of which were able to form mycelia (6406 and MEN) and two of which were not (MM2002 and CA2). The expression of the coaggregation adhesin during yeast cell starvation was inhibited by addition of trichodermin or amphotericin B. The strains of S. sanguis, Streptococcus gordonii, and Streptococcus oralis tested for coaggregating activity encompassed a diverse range of physiological and morphological types, yet all exhibited saturable coaggregation with starved C. albicans cells. There was no correlation of cell surface hydrophobicity, of either yeast or streptococcal cells, with their abilities to coaggregate. Strains of Streptococcus anginosus also coaggregated with starved yeast cells; Streptococcus salivarius and Streptococcus pyogenes coaggregated to a lesser degree with C. albicans, and the coaggregation with S. pyogenes was not promoted by yeast cell starvation; Streptococcus mutans and Enterococcus faecalis did not coaggregate with yeast. The coaggregation reactions of S. sanguis and S. gordonii with C. albicans were inhibited by EDTA and by heat or protease treatment of the yeast cells and were not reversible by the addition of lactose or other simple sugars. These observations extend the range of intergeneric coaggregations that are known to occur between oral microbes and suggest that coaggregations of C. albicans with viridans group streptococci may be important for colonization of oral surfaces by the yeast. PMID:2182544

  8. Group A Streptococcus: a re-emergent pathogen. Infectious Diseases and Immunization Committee, Canadian Paediatric Society.

    PubMed Central

    1993-01-01

    Rheumatic fever is still rare in North America but must continue to be considered in the appropriate clinical setting. Invasive or severe GABHS disease remains unusual and is unlikely to be missed by the practitioner; however, it is essential that GABHS infection be considered as a possible cause of a severe sepsis-like syndrome. Currently the routine management of GABHS infection is unchanged; however, heightened awareness of the infection's rare, more serious complications is needed. PMID:8500028

  9. Splenectomy Correlates With Increased Risk of Pyogenic Liver Abscess: A Nationwide Cohort Study in Taiwan

    PubMed Central

    Lai, Shih-Wei; Lai, Hsueh-Chou; Lin, Cheng-Li; Liao, Kuan-Fu

    2015-01-01

    Objectives Little is known about the risk of pyogenic liver abscess in patients with splenectomy. We explored the relationship between splenectomy and pyogenic liver abscess in Taiwan. Methods We conducted a nationwide cohort analysis using the hospitalization dataset of the Taiwan National Health Insurance Program. We included 17 779 subjects aged 20–84 years who underwent splenectomy in 1998 to 2010 (splenectomy group) and 70 855 randomly selected subjects without splenectomy (non-splenectomy group). Both groups were matched by sex, age, other comorbidities, and hospitalization year of receiving splenectomy. The incidence of pyogenic liver abscess at the end of 2011 was measured. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratios and 95% confidence intervals for pyogenic liver abscess associated with splenectomy and other comorbidities. Results The overall incidence rate was 3.75-fold higher in the splenectomy group than that in the non-splenectomy group (2.15 vs 0.57 per 1000 person-years; 95% confidence interval, 3.57–3.94). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscess was 3.89 in subjects with splenectomy (95% confidence interval, 3.20–4.72) when compared with subjects without splenectomy. In further analysis, the hazard ratio markedly increased to 14.34 for those with splenectomy and having any of the assessed comorbidities, including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus (95% confidence interval, 10.61–19.39). Conclusions Patients with splenectomy are at an increased risk of developing pyogenic liver abscess, particularly when they have comorbid conditions. PMID:26256773

  10. Comparison of Pyogenic Spondylitis and Tuberculous Spondylitis

    PubMed Central

    2014-01-01

    Pyogenic spondylitis and tuberculous spondylitis are common causes of spinal infection. It is difficult to differentiate tuberculous spondylitis and pyogenic spondylitis clinically and radiologically. Recently magnetic resonance imaging has been reported to be beneficial for early diagnosis and differential diagnosis of the spondylitis, and is being used extensively for diagnosis. However, the diagnosis must be considered in combination with corresponding changes in clinical manifestations, radiological findings, blood and tissue cultures and histopathological findings. Conservative treatments, including antimicrobial medications, are started initially. Surgical treatments, which include anterior or posterior approach, single-stage or two-stage surgery, with or without instrumentation, may be performed as indicated. PMID:24761207

  11. Ampicillin-sulbactam therapy for multiple pyogenic hepatic abscesses.

    PubMed

    Zenon, G J; Cadle, R M; Hamill, R J

    1990-12-01

    A patient with multiple, pyogenic hepatic abscesses is described, and the pathophysiology, etiologies, clinical and laboratory manifestations, and management of the disease are reviewed. A 55-year-old man with a history of ethanol abuse and pancreatitis developed fever, chills, general malaise, and right upper quadrant abdominal pain two weeks before hospitalization. Baseline laboratory and hematology results included serum albumin concentration, 3.2 g/dL; serum alkaline phosphatase concentration, 239 mIU/mL; total serum bilirubin concentration, 1.3 mg/dL; white blood cell count, 18,400/cu mm; red blood cell count, 4.7 million/cu mm; hemoglobin, 12.5 g/dL; and hematocrit, 38.8%. Abdominal ultrasound showed echo-free cavities throughout the hepatic parenchyma; abdominal computed-tomography (CT) scan showed hepatomegaly and multiple radiolucent spaces. CT-guided needle aspiration of a hepatic mass yielded purulent material that grew Fusobacterium necrophorum under anaerobic conditions. On day 7, the patient was started on i.v. ampicillin sodium-sulbactam sodium. A CT scan two weeks later showed a reduction in the number and sizes of abscesses. The patient continued i.v. therapy for one month, then was discharged on a regimen of p.o. amoxicillin trihydrate-clavulanate potassium. Hepatic abscesses are either amebic or pyogenic; the latter usually has a higher mortality. The etiologies of pyogenic hepatic abscesses include ascending cholangitis, portal vein bacteremia, systemic bacteremia, extension from a contiguous focus of infection, and trauma. Diagnosis is difficult and relies highly on clinical suspicion. Clinical symptoms include hepatomegaly, fever, chills, and malaise. Abnormal laboratory values include leukocytosis, anemia, and hypoalbuminemia. The abscesses are frequently polymicrobial; Escherichia coli is the most commonly isolated species. CT is the best radiological technique for diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2292177

  12. TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus?

    PubMed Central

    Leday, Temekka V.; Gold, Kathryn M.; Kinkel, Traci L.; Roberts, Samantha A.; Scott, June R.; McIver, Kevin S.

    2008-01-01

    Coordinate regulation of virulence factors by the group A streptococcus (GAS) Streptococcus pyogenes is important in this pathogen's ability to cause disease. To further elucidate the regulatory network in this human pathogen, the CovR-repressed two-component system (TCS) trxSR was chosen for further analysis based on its homology to a virulence-related TCS in Streptococcus pneumoniae. In a murine skin infection model, an insertion mutation in the response regulator gene, trxR, led to a significant reduction in lesion size, lesion severity, and lethality. Curing the trxR mutation restored virulence comparable to the wild-type strain. The trxSR operon was defined in vivo, and CovR was found to directly repress its promoter in vitro. DNA microarray analysis established that TrxR activates transcription of Mga-regulated virulence genes, which may explain the virulence attenuation of the trxR mutant. This regulation appears to occur by activation of the mga promoter, Pmga, as demonstrated by analysis of a luciferase reporter fusion. Complementation of the trxR mutant with trxR on a plasmid restored expression of Mga regulon genes and restored virulence in the mouse model to wild-type levels. TrxR is the first TCS shown to regulate Mga expression. Because it is CovR repressed, TrxR defines a new pathway by which CovR can influence Mga to affect pathogenesis in the GAS. PMID:18678666

  13. Study of streptococcal hemoprotein receptor (Shr) in iron acquisition and virulence of M1T1 group A streptococcus

    PubMed Central

    Dahesh, Samira; Nizet, Victor; Cole, Jason N.

    2012-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is a human bacterial pathogen of global significance, causing severe invasive diseases associated with serious morbidity and mortality. To survive within the host and establish an infection, GAS requires essential nutrients, including iron. The streptococcal hemoprotein receptor (Shr) is a surface-localized GAS protein that binds heme-containing proteins and extracellular matrix components. In this study, we employ targeted allelic exchange mutagenesis to investigate the role of Shr in the pathogenesis of the globally disseminated serotype M1T1 GAS. The shr mutant exhibited a growth defect in iron-restricted medium supplemented with ferric chloride, but no significant differences were observed in neutrophil survival, antimicrobial peptide resistance, cell surface charge, fibronectin-binding or adherence to human epithelial cells and keratinocytes, compared with wild-type. However, the shr mutant displayed a reduction in human blood proliferation, laminin-binding capacity and was attenuated for virulence in in vivo models of skin and systemic infection. We conclude that Shr augments GAS adherence to laminin, an important extracellular matrix attachment component. Furthermore, Shr-mediated iron uptake contributes to GAS growth in human blood, and is required for full virulence of serotype M1T1 GAS in mouse models of invasive disease. PMID:23076332

  14. Molecular typing methods for outbreak detection and surveillance of invasive disease caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, a review

    PubMed Central

    Harrison, Odile B.; Brueggemann, Angela B.; Caugant, Dominique A.; van der Ende, Arie; Frosch, Matthias; Gray, Stephen; Heuberger, Sigrid; Krizova, Paula; Olcen, Per; Slack, Mary; Taha, Muhamed-Kheir; Maiden, Martin C. J

    2014-01-01

    Invasive disease caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae remains an important cause of morbidity and mortality worldwide, despite the introduction of successful conjugate polysaccharide vaccines that target disease-associated strains. In addition, resistance, or more accurately reduced susceptibility, to therapeutic antibiotics is spreading in populations of these organisms. There is therefore a continuing requirement for the surveillance of vaccine and non-vaccine antigens and antibiotic susceptibilities among isolates from invasive disease, which is only partially met by conventional methods. This need can be met with molecular and especially nucleotide sequence-based typing methods, which are fully developed in the case of N. meningitidis and which could be more widely deployed in clinical laboratories for S. pneumoniae and H. influenzae. PMID:21622526

  15. Habitat, wildlife, and one health: Arcanobacterium pyogenes in Maryland and Upper Eastern Shore white-tailed deer populations

    PubMed Central

    Turner, Melissa M.; DePerno, Christopher S.; Conner, Mark C.; Eyler, T. Brian; Lancia, Richard A.; Klaver, Robert W.; Stoskopf, Michael K.

    2013-01-01

    Background Understanding the distribution of disease in wildlife is key to predicting the impact of emerging zoonotic one health concerns, especially for wildlife species with extensive human and livestock interfaces. The widespread distribution and complex interactions of white-tailed deer (Odocoileus virginianus) with humans suggest deer population health and management may have implications beyond stewardship of the animals. The intracranial abscessation suppurative meningitis (IASM) disease complex in deer has been linked to Arcanobacterium pyogenes, an under-diagnosed and often misdiagnosed organism considered commensal in domestic livestock but associated with serious disease in numerous species, including humans. Methods Our study used standard bacterial culture techniques to assess A. pyogenes prevalence among male deer sampled across six physiogeographic regions in Maryland and male and female deer in the Upper Eastern Shore under Traditional Deer Management (TDM) and Quality Deer Management (QDM), a management protocol that alters population demographics in favor of older male deer. Samples were collected from antler pedicles for males, the top of the head where pedicles would be if present for females, or the whole dorsal frontal area of the head for neonates. We collected nasal samples from all animals by swabbing the nasopharyngeal membranes. A gram stain and catalase test were conducted, and aerobic bacteria were identified to genus and species when possible. We evaluated the effect of region on whether deer carried A. pyogenes using Pearson's chi-square test with Yates’ continuity correction. For the white-tailed deer management study, we tested whether site, age class and sex predisposed animals to carrying A. pyogenes using binary logistic regression. Results A. pyogenes was detected on deer in three of the six regions studied, and was common in only one region, the Upper Eastern Shore. In the Upper Eastern Shore, 45% and 66% of antler and nasal swabs from deer were positive for A. pyogenes, respectively. On the Upper Eastern Shore, prevalence of A. pyogenes cultured from deer did not differ between management areas, and was abundant among both sexes and across all age classes. No A. pyogenes was cultured from a small sample of neonates. Conclusion Our study indicates A. pyogenes may be carried widely among white-tailed deer regardless of sex or age class, but we found no evidence the pathogen is acquired in utero. The distribution of A. pyogenes across regions and concentration in a region with low livestock levels suggests the potential for localized endemicity of the organism and the possibility that deer may serve as a maintenance reservoir for an emerging one health concern. PMID:23930157

  16. Salivaricin 9, a new lantibiotic produced by Streptococcus salivarius.

    PubMed

    Wescombe, P A; Upton, M; Renault, P; Wirawan, R E; Power, D; Burton, J P; Chilcott, C N; Tagg, J R

    2011-05-01

    Salivaricin 9 (Sal9) is a 2560 Da lantibiotic having just 46 % amino acid identity with its closest known homologue, the Streptococcus pyogenes lantibiotic SA-FF22. The Sal9 locus (designated siv) in Streptococcus salivarius strain 9 was partially sequenced and localized to an approximately 170 kb megaplasmid, which also harbours the locus for the lantibiotic salivaricin A4. The entire locus was fully characterized in the draft genome sequence of S. salivarius strain JIM8780 and shown to consist of eight genes, having the following putative functions: sivK, sensor kinase; sivR, response regulator; sivA, Sal9 precursor peptide; sivM, lantibiotic modification enzyme; sivT, ABC transporter involved in the export of Sal9 and concomitant cleavage of its leader peptide; and sivFEG, encoding lantibiotic self-immunity. Intriguingly, in contrast to strain 9, the siv locus was chromosomally located in strain JIM8780--the first lantibiotic locus shown not to be exclusively plasmid-associated in S. salivarius. Sal9-containing extracts specifically induced lantibiotic production in both strain 9 and strain JIM8780, indicating that Sal9 functions as a signal peptide for upregulation of its own biosynthesis. Screening representative strains of three streptococcal species (S. salivarius, S. pyogenes and S. mitis) for sivA indicated that it was present only in S. salivarius, with 12 of 28 tested S. salivarius positive. Since Sal9 was inhibitory to all tested S. pyogenes strains it appears to have potential as an important component of the bacteriocin armoury of S. salivarius probiotics intended to control S. pyogenes infections of the human oral cavity. PMID:21310787

  17. Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: An integrin-binding cysteine protease

    PubMed Central

    Kagawa, Todd F.; Cooney, Jakki C.; Baker, Heather M.; McSweeney, Sean; Liu, Mengyao; Gubba, Siddeswar; Musser, James M.; Baker, Edward N.

    2000-01-01

    Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors. We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, including necrotizing fasciitis. The structure, determined for the 40-kDa precursor form of SpeB at 1.6-? resolution, reveals that the protein is a distant homologue of the papain superfamily that includes the mammalian cathepsins B, K, L, and S. Despite negligible sequence identity, the protease portion has the canonical papain fold, albeit with major loop insertions and deletions. The catalytic site differs from most other cysteine proteases in that it lacks the Asn residue of the Cys-His-Asn triad. The prosegment has a unique fold and inactivation mechanism that involves displacement of the catalytically essential His residue by a loop inserted into the active site. The structure also reveals the surface location of an integrin-binding Arg-Gly-Asp (RGD) motif that is a feature unique to SpeB among cysteine proteases and is linked to the pathogenesis of the most invasive strains of S. pyogenes. PMID:10681429

  18. Extragingival pyogenic granuloma histologically mimicking capillary hemangioma

    PubMed Central

    Dahiya, Ritu; Kathuria, Abhinav

    2014-01-01

    Pyogenic granuloma is a tumor-like proliferation to a non-specific infection. The tumor-like growth is considered to be non-neoplastic in nature and presents in various clinical and histological forms in the oral cavity. Hemangiomas are benign vascular anomalies characterized by benign proliferation of blood vessels. The aim of this article is to drive attention toward the uncommon location of capillary hemangioma on the palate. In spite of their benign nature, intraoral capillary hemangiomas are always clinically important to be diagnosed well in time and suitably managed. The lesion in the present case although clinically diagnosed as pyogenic granuloma gave a histological picture of capillary hemangioma when surgically excised. PMID:25425828

  19. Recurrent pyogenic granuloma with a satellite lesion.

    PubMed

    Rana, Ritu; Ramachandra, Srinivas Sulugodu; Prasad, Umesh Chandra; Aggarwal, Pankaj; Dayakara, Jithendra Kajoor

    2015-08-01

    Pyogenic granuloma (PG) is a tumorlike growth of the oral mucosa or skin that is considered to be an exaggerated conditioned response to minor trauma. It usually is painless, bleeds easily, and is considered to be nonneoplastic in nature. Pyogenic granuloma predominantly occurs in the second decade of life, mostly among young adult females. Clinically, it is a smooth or lobulated exophytic lesion manifesting as small, red, erythematous papules on a pedunculated or sometimes sessile base that usually is hemorrhagic. We report the case of 30-year-old woman who presented with a PG in the anterior palatal region during pregnancy that recurred with a satellite lesion 1 year following surgical excision. PMID:26367761

  20. Antimicrobial Resistance Profile and Genotypic Characteristics of Streptococcus suis Capsular Type 2 Isolated from Clinical Carrier Sows and Diseased Pigs in China

    PubMed Central

    Zhang, Chunping; Zhang, Zhongqiu; Song, Li; Fan, Xuezheng; Wen, Fang; Xu, Shixin; Ning, Yibao

    2015-01-01

    Streptococcus suis serotype 2 is an important zoonotic pathogen. Antimicrobial resistance phenotypes and genotypic characterizations of S. suis 2 from carrier sows and diseased pigs remain largely unknown. In this study, 96 swine S. suis type 2, 62 from healthy sows and 34 from diseased pigs, were analyzed. High frequency of tetracycline resistance was observed, followed by sulfonamides. The lowest resistance of S. suis 2 for β-lactams supports their use as the primary antibiotics to treat the infection of serotype 2. In contrast, 35 of 37 S. suis 2 with MLSB phenotypes were isolated from healthy sows, mostly encoded by the ermB and/or the mefA genes. Significantly lower frequency of mrp+/epf+/sly+ was observed among serotype 2 from healthy sows compared to those from diseased pigs. Furthermore, isolates from diseased pigs showed more homogeneously genetic patterns, with most of them clustered in pulsotypes A and E. The data indicate the genetic complexity of S. suis 2 between herds and a close linkage among isolates from healthy sows and diseased pigs. Moreover, many factors, such as extensive use of tetracycline or diffusion of Tn916 with tetM, might have favored for the pathogenicity and widespread dissemination of S. suis serotype 2. PMID:26064892

  1. Pyogenic Vertebral Osteomyelitis in Heroin Addicts

    PubMed Central

    Fishbach, Ronald S.; Rosenblatt, Jon E.; Dahlgren, James G.

    1973-01-01

    The diagnosis of pyogenic vertebral osteomyelitis was made in seven narcotic addicts between 1967 and 1972. Vertebrae involved were either cervical or lumbar. Bacteriologic diagnosis was made in each case by percutaneous needle biopsy and aspiration. Staphylococcus aureus was cultured in two patients. Five patients had infections due to Gram-negative bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter. All patients were cured by treatment with antibiotics and immobilization. PMID:4199351

  2. Pyogenic Sacroiliitis in a 13-Month-Old Child: A Case Report and Literature Review.

    PubMed

    Leroux, Julien; Julien, Leroux; Bernardini, Isabelle; Isabelle, Bernardini; Grynberg, Lucie; Lucie, Grynberg; Grandguillaume, Claire; Claire, Grandguillaume; Michelin, Paul; Paul, Michelin; Ould Slimane, Mourad; Slimane, Ould Slimane; Nectoux, Eric; Eric, Nectoux; Deroussen, François; François, Deroussen; Gouron, Richard; Richard, Gouron; Angelliaume, Audrey; Audrey, Angelliaume; Ilharreborde, Brice; Brice, Ilharreborde; Renaux-Petel, Mariette; Mariette, Renaux-Petel

    2015-10-01

    Pyogenic sacroiliitis is exceptional in very young children. Diagnosis is difficult because clinical examination is misleading. FABER test is rarely helpful in very young children. Inflammatory syndrome is frequent. Bone scintigraphy and MRI are very sensitive for the diagnosis. Joint fluid aspiration and blood cultures are useful to identify the pathogen. Appropriate antibiotic therapy provides rapid regression of symptoms and healing. We report the case of pyogenic sacroiliitis in a 13-month-old child.Clinical, biological, and imaging data of this case were reviewed and reported retrospectively.A 13-month-old girl consulted for decreased weight bearing without fever or trauma. Clinical examination was not helpful. There was an inflammatory syndrome. Bone scintigraphy found a sacroiliitis, confirmed on MRI. Aspiration of the sacroiliac joint was performed. Empiric intravenous biantibiotic therapy was started. Patient rapidly recovered full weight bearing. On the 5th day, clinical examination and biological analysis returned to normal. Intravenous antibiotic therapy was switched for oral. One month later, clinical examination and biological analysis were normal and antibiotic therapy was stopped.Hematogenous osteoarticular infections are common in children but pyogenic sacroiliitis is rare and mainly affects older children. Diagnosis can be difficult because clinical examination is poor. Moreover, limping and decreased weight bearing are very common reasons for consultation. This may delay the diagnosis or refer misdiagnosis. Bone scintigraphy is useful to locate a bone or joint disease responsible for limping. In this observation, bone scintigraphy located the infection at the sacroiliac joint. Given the young age, MRI was performed to confirm the diagnosis. Despite the very young age of the patient, symptoms rapidly disappeared with appropriate antibiotic therapy.We report the case of pyogenic sacroiliitis in a 13-month-old child. It reminds the risk of misdiagnosing pyogenic sacroiliitis in children because it is exceptional and clinical examination is rarely helpful. It also highlights the usefulness of bone scintigraphy and MRI in osteoarticular infections in children. PMID:26496260

  3. Spectroscopic Method for Fast and Accurate Group A Streptococcus Bacteria Detection.

    PubMed

    Schiff, Dillon; Aviv, Hagit; Rosenbaum, Efraim; Tischler, Yaakov R

    2016-02-16

    Rapid and accurate detection of pathogens is paramount to human health. Spectroscopic techniques have been shown to be viable methods for detecting various pathogens. Enhanced methods of Raman spectroscopy can discriminate unique bacterial signatures; however, many of these require precise conditions and do not have in vivo replicability. Common biological detection methods such as rapid antigen detection tests have high specificity but do not have high sensitivity. Here we developed a new method of bacteria detection that is both highly specific and highly sensitive by combining the specificity of antibody staining and the sensitivity of spectroscopic characterization. Bacteria samples, treated with a fluorescent antibody complex specific to Streptococcus pyogenes, were volumetrically normalized according to their Raman bacterial signal intensity and characterized for fluorescence, eliciting a positive result for samples containing Streptococcus pyogenes and a negative result for those without. The normalized fluorescence intensity of the Streptococcus pyogenes gave a signal that is up to 16.4 times higher than that of other bacteria samples for bacteria stained in solution and up to 12.7 times higher in solid state. This method can be very easily replicated for other bacteria species using suitable antibody-dye complexes. In addition, this method shows viability for in vivo detection as it requires minute amounts of bacteria, low laser excitation power, and short integration times in order to achieve high signal. PMID:26752013

  4. Comparison of Gen-Probe Group A streptococcus Direct Test with culture for diagnosing streptococcal pharyngitis.

    PubMed

    Pokorski, S J; Vetter, E A; Wollan, P C; Cockerill, F R

    1994-06-01

    The Group A Streptococcus Direct Test (GP-ST test; Gen-Probe, Inc., San Diego, Calif.) was compared with culture for the detection of Streptococcus pyogenes from throat swabs of 767 patients with pharyngitis. Swabs were tested by the GP-ST test after inoculating a 5% sheep blood agar (SBA) plate. SBA plates were incubated at 35 degrees C in room air for 72 h. SBA plates with no evidence of beta-hemolytic colonies after 18 to 24 h of incubation were subcultured by taking a swipe across the primary inoculum from the SBA plate to an agar selective for Streptococcus spp. In a low-prevalence (11.9%) population and in comparison with the number of positive cultures detected by the 72-h single-culture method (SBA plate method), the GP-ST test had a sensitivity of 88.6%, a specificity of 97.8%, a positive predictive value of 83.9%, and a negative predictive value of 98.5%. In comparison with the growth of any colonies of S. pyogenes on the 72-h SBA plates plus a subculture onto selective blood agar, the sensitivities and specificities were as follows: 72-h SBA plate method, 96.7 and 100%, respectively; GP-ST test, 85.7 and 97.8%, respectively. The GP-ST test is an easy-to-perform, reliable test for batch screening of throat swabs for S. pyogenes. PMID:8077386

  5. Antimicrobial susceptibility of Arcanobacterium pyogenes isolated from the lungs of white-tailed deer (Odocoileus virginianus) with pneumonia.

    PubMed

    Tell, Lisa A; Brooks, Jason W; Lintner, Valerie; Matthews, Tammy; Kariyawasam, Subhashinie

    2011-09-01

    In vitro susceptibilities of 29 strains of Arcanobacterium pyogenes isolated from lung lesions of white-tailed deer (Odocoileus virginianus) with pneumonia were determined using the broth microdilution method to ascertain efficacious treatment options for pneumonic white-tailed deer. All 29 A. pyogenes strains tested were susceptible to ceftiofur, spectinomycin, tiamulin, and trimethoprim-sulfamethoxazole but were resistant to both danofloxacin and sulfadimethoxine. Likewise, all 29 isolates were either fully susceptible or intermediately susceptible to gentamicin (25 susceptible; 4 intermediate) and tulathromycin (25 susceptible; 4 intermediate). At least one isolate of A. pyogenes tested was resistant to ampicillin, chlortetracycline, clindamycin, enrofloxacin, florfenicol, oxytetracycline, penicillin, and tilmicosin suggesting their ineffectiveness in treating A. pyogenes-associated lung infections in white-tailed deer. Minimum inhibitory concentration (MIC) data for tylosin and neomycin could not be interpreted due to unavailability of Clinical and Laboratory Standards Institute (CLSI)-approved breakpoints for these 2 agents. In summary, based on MIC values, ceftiofur, spectinomycin, tiamulin, and trimethoprim-sulfamethoxazole are more efficacious than other antimicrobial agents for treating A. pyogenes-related pneumonia in white-tailed deer. However, ceftiofur may be preferred over the other 4 drugs as it is being widely used to treat respiratory disease in cattle and other animal species, as well as is available for single dose parenteral administration. PMID:21908365

  6. Intra-Abscess Administration of Antibiotics Through UltrasoundGuided Percutaneous Catheter for the Treatment of Pyogenic Liver Abscess

    PubMed Central

    Alvarez-Uria, Gerardo; Pakam, Raghavakalyan; Midde, Manoranjan; Naik, Praveen Kumar

    2013-01-01

    Pyogenic liver abscess is a potentially life-threatening disease. The treatment of a pyogenic liver abscess usually involves ultrasound guided percutaneous drainage because of the poor penetration of the systemic administration of antibiotics inside the abscess. However, a sizable proportion of patients will necessitate surgical interventions, which involves high peri- and post-operative risks. Theoretically, the local instillation of antibiotics inside the pyogenic liver abscess fluid could achieve a high concentration of the antibiotic for a long period of time. This could be especially beneficial for time-dependent bactericidal antibiotics such as beta-lactams, because their bactericidal effectiveness depends on the amount of time that bacteria are exposed to the antibiotic. We are reporting two patients with complicated pyogenic liver abscesses, who were successfully treated with systemic antibiotics and local instillation of meropenem inside the cavities of the abscesses. These cases suggest that the local instillation of the beta-lactam antibiotics could be an effective and a safe strategy for the treatment of pyogenic liver abscesses that cannot be completely drained through an ultrasound guided percutaneous catheter. PMID:24086880

  7. Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome.

    PubMed Central

    Johnson, Abdul-Wahab B. R.; Adedoyin, Olanrewaju T.; Abdul-Karim, Aishat A.; Olanrewaju, Abdul-Waheed I.

    2007-01-01

    The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram-positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram-smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion. PMID:17722674

  8. Molecular phylogeny and a taxonomic proposal for the genus Streptococcus.

    PubMed

    Póntigo, F; Moraga, M; Flores, S V

    2015-01-01

    Alternative phylogenies for the genus Streptococcus have been proposed due to uncertainty about the among-species group relationships. Here, we performed a phylogenetic analysis of the genus Streptococcus, considering all the species groups and also the genomic data accumulated by other studies. Seventy-five species were subjected to a Bayesian phylogenetic analysis using sequences from eight genes (16S rRNA, rpoB, sodA, tuf, rnpB, gyrB, dnaJ, and recN). On the basis of our results, we propose a new Phylogeny for the genus, with special emphasis on the inter-species group level. This new phylogeny differs from those suggested previously. From topological and evolutionary distance criteria, we propose that gordonii, pluranimalium, and sobrinus should be considered as new species groups, in addition to the currently recognized groups of mutans, bovis, pyogenic, suis, mitis, and salivarius. PMID:26400318

  9. Characterization and Protective Immunogenicity of the SzM Protein of Streptococcus zooepidemicus NC78 from a Clonal Outbreak of Equine Respiratory Disease

    PubMed Central

    Velineni, Sridhar

    2013-01-01

    Streptococcus zooepidemicus of Lancefield group C is a highly variable tonsillar and mucosal commensal that usually is associated with opportunistic infections of the respiratory tract of vertebrate hosts. More-virulent clones have caused epizootics of severe respiratory disease in dogs and horses. The virulence factors of these strains are poorly understood. The antiphagocytic protein SeM is a major virulence factor and protective antigen of Streptococcus equi, a clonal biovar of an ancestral S. zooepidemicus strain. Although the genome of S. zooepidemicus strain H70, an equine isolate, contains a partial homolog (szm) of sem, expression of the gene has not been documented. We have identified and characterized SzM from an encapsulated S. zooepidemicus strain from an epizootic of equine respiratory disease in New Caledonia. The SzM protein of strain NC78 (SzMNC78) has a predicted predominantly alpha-helical fibrillar structure with an LPSTG cell surface anchor motif and resistance to hot acid. A putative binding site for plasminogen is present in the B repeat region, the sequence of which shares homology with repeats of the plasminogen binding proteins of human group C and G streptococci. Equine plasminogen is activated in a dose-dependent manner by recombinant SzMNC78. Only 23.20 and 25.46% DNA homology is shared with SeM proteins of S. equi strains CF32 and 4047, respectively, and homology ranges from 19.60 to 54.70% for SzM proteins of other S. zooepidemicus strains. As expected, SzMNC78 reacted with convalescent-phase sera from horses with respiratory disease associated with strains of S. zooepidemicus. SzMNC78 resembles SeM in binding equine fibrinogen and eliciting strong protective antibody responses in mice. Sera of vaccinated mice opsonized S. zooepidemicus strains NC78 and W60, the SzM protein of which shared partial amino acid homology with SzMNC78. We conclude that SzM is a protective antigen of NC78; it was strongly reactive with serum antibodies from horses during recovery from S. zooepidemicus-associated respiratory disease. PMID:23740925

  10. Actinomyces pyogenes septic arthritis in a diabetic farmer.

    PubMed

    Lynch, M; O'Leary, J; Murnaghan, D; Cryan, B

    1998-07-01

    We report a case of septic arthritis and osteomyelitis of the left ankle due to Actinomyces pyogenes in a diabetic farmer. Few confirmed human cases of A. pyogenes infection have been reported, partly because of inadequate identification of this bacterium. Bacteriological characteristics of the organism, which resembles Arcanobacterium haemolyticum, are described with a review of previous case reports. PMID:9733386

  11. 40 CFR 725.421 - Introduced genetic material.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Listeria monocytogenes Listeriolysin (A B) Streptococcus pneumoniae Pneumolysin Streptococcus pyogene... Leucocidin (leukocidin, cytotoxin) Streptococcus pyogenes Streptolysin S (SLS); Erythrogenic toxins...

  12. 40 CFR 725.421 - Introduced genetic material.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Listeria monocytogenes Listeriolysin (A B) Streptococcus pneumoniae Pneumolysin Streptococcus pyogene... Leucocidin (leukocidin, cytotoxin) Streptococcus pyogenes Streptolysin S (SLS); Erythrogenic toxins...

  13. 40 CFR 725.421 - Introduced genetic material.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Listeria monocytogenes Listeriolysin (A B) Streptococcus pneumoniae Pneumolysin Streptococcus pyogene... Leucocidin (leukocidin, cytotoxin) Streptococcus pyogenes Streptolysin S (SLS); Erythrogenic toxins...

  14. 40 CFR 725.421 - Introduced genetic material.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Listeria monocytogenes Listeriolysin (A B) Streptococcus pneumoniae Pneumolysin Streptococcus pyogene... Leucocidin (leukocidin, cytotoxin) Streptococcus pyogenes Streptolysin S (SLS); Erythrogenic toxins...

  15. 40 CFR 725.421 - Introduced genetic material.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Listeria monocytogenes Listeriolysin (A B) Streptococcus pneumoniae Pneumolysin Streptococcus pyogene... Leucocidin (leukocidin, cytotoxin) Streptococcus pyogenes Streptolysin S (SLS); Erythrogenic toxins...

  16. Behcet's Disease

    MedlinePLUS

    ... Behçet’s disease. They are particularly interested in whether Streptococcus, the bacterium that causes strep throat, is associated ... the eye and the reproductive and urinary tracts. Streptococcus. A bacterium that causes infections such as strep ...

  17. Pneumococcal Disease

    MedlinePLUS

    ... Marketing Share this: Main Content Area Pneumococcal Disease Streptococcus pneumoniae are bacteria frequently found in the upper ... T et al . Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children ...

  18. Modern management of pyogenic hepatic abscess: a case series and review of the literature

    PubMed Central

    2011-01-01

    Background Pyogenic hepatic abscesses are relatively rare, though untreated are uniformly fatal. A recent paradigm shift in the management of liver abscesses, facilitated by advances in diagnostic and interventional radiology, has decreased mortality rates. The aim of this study was to review our experience in managing pyogenic liver abscess, review the literature in this field, and propose guidelines to aid in the current management of this complex disease. Methods Demographic and clinical details of all patients admitted to a single institution with liver abscess over a 5 year period were reviewed. Clinical presentation, aetiology, diagnostic work-up, treatment, morbidity and mortality data were collated. Results Over a 5 year period 11 patients presented to a single institution with pyogenic hepatic abscess (55% males, mean age 60.3 years). Common clinical features at presentation were non-specific constitutional symptoms and signs. Aetiology was predominantly gallstones (45%) or diverticular disease (27%). In addition to empiric antimicrobial therapy, all patients underwent radiologically guided percutaneous drainage of the liver abscess at diagnosis and only 2 patients required surgical intervention, including one 16-year old female who underwent hemi-hepatectomy for a complex and rare Actinomycotic abscess. There were no mortalities after minimum follow-up of one year. Conclusions Pyogenic liver abscesses are uncommon, and mortality has decreased over the last two decades. Antimicrobial therapy and radiological intervention form the mainstay of modern treatment. Surgical intervention should be considered for patients with large, complex, septated or multiple abscesses, underlying disease or in whom percutaneous drainage has failed. PMID:21435221

  19. Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess

    PubMed Central

    Liao, Kuan-Fu; Lin, Cheng-Li; Lai, Shih-Wei; Chen, Wen-Chi

    2015-01-01

    Abstract The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted ?7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess. After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance. Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem. PMID:26266369

  20. covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus

    PubMed Central

    Ashwinkumar Subramenium, Ganapathy; Viszwapriya, Dharmaprakash; Iyer, Prasanth Mani; Balamurugan, Krishnaswamy; Karutha Pandian, Shunmugiah

    2015-01-01

    Background Group A streptococcus (GAS, Streptococcus pyogenes), a multi-virulent, exclusive human pathogen responsible for various invasive and non-invasive diseases possesses biofilm forming phenomenon as one of its pathogenic armaments. Recently, antibiofilm agents have gained prime importance, since inhibiting the biofilm formation is expected to reduce development of antibiotic resistance and increase their susceptibility to the host immune cells. Principal Findings The current study demonstrates the antibiofilm activity of 3Furancarboxaldehyde (3FCA), a floral honey derived compound, against GAS biofilm, which was divulged using crystal violet assay, light microscopy, and confocal laser scanning microscopy. The report is extended to study its effect on various aspects of GAS (morphology, virulence, aggregation) at its minimal biofilm inhibitory concentration (132μg/ml). 3FCA was found to alter the growth pattern of GAS in solid and liquid medium and increased the rate of auto-aggregation. Electron microscopy unveiled the increase in extra polymeric substances around cell. Gene expression studies showed down-regulation of covR gene, which is speculated to be the prime target for the antibiofilm activity. Increased hyaluronic acid production and down regulation of srtB gene is attributed to the enhanced rate of auto-aggregation. The virulence genes (srv, mga, luxS and hasA) were also found to be over expressed, which was manifested with the increased susceptibility of the model organism Caenorhabditis elegans to 3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C. elegans. Significance Though 3FCA possess antibiofilm activity against GAS, it was also found to increase the virulence of GAS. This study demonstrates that, covR mediated antibiofilm activity may increase the virulence of GAS. This also emphasizes the importance to analyse the acclimatization response and virulence of the pathogen in the presence of antibiofilm compounds prior to their clinical trials. PMID:25978065

  1. Pyogenic Bacterial Infections in Humans with MyD88 Deficiency

    PubMed Central

    von Bernuth, Horst; Picard, Capucine; Jin, Zhongbo; Pankla, Rungnapa; Xiao, Hui; Ku, Cheng-Lung; Chrabieh, Maya; Mustapha, Imen Ben; Ghandil, Pegah; Camcioglu, Yildiz; Vasconcelos, Jlia; Sirvent, Nicolas; Guedes, Margarida; Vitor, Artur Bonito; Herrero-Mata, Mara Jos; Arstegui, Juan Ignacio; Rodrigo, Carlos; Alsina, Laia; Ruiz-Ortiz, Estibaliz; Juan, Manel; Fortuny, Claudia; Yage, Jordi; Antn, Jordi; Pascal, Mariona; Chang, Huey-Hsuan; Janniere, Lucile; Rose, Yoann; Garty, Ben-Zion; Chapel, Helen; Issekutz, Andrew; Mardi, Lszl; Rodriguez-Gallego, Carlos; Banchereau, Jacques; Abel, Laurent; Li, Xiaoxia; Chaussabel, Damien; Puel, Anne; Casanova1, Jean-Laurent

    2009-01-01

    MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections. PMID:18669862

  2. Hematogenous pyogenic vertebral osteomyelitis: diagnostic value of radionuclide bone imaging

    SciTech Connect

    Adatepe, M.H.; Powell, O.M.; Isaacs, G.H.; Nichols, K.; Cefola, R.

    1986-11-01

    Hematogenous pyogenic vertebral osteomyelitis (HPVO) continues to be a diagnostic problem for clinicians due to nonspecific presentation of the disease (1,2). We reviewed our experience of the last 10 years to determine the diagnostic usefulness of radionuclide bone studies in this disease. We found 15 patients whose primary diagnosis was HPVO. Of the 15 patients, 12 had (99mTc)MDP bone scans which were all positive. Five of the 12 patients had positive (/sup 67/Ga)citrate scans and one patient with chronic active HPVO had negative /sup 67/Ga and (/sup 111/In)WBC bone images. At the same time, three patients' spine x-rays and one patient's CT scan of the vertebra were normal. Additionally, in three patients spine x-rays were interpreted as consistent with degenerative joint disease that contributed to the delay of the diagnosis. We conclude that when HPVO is suspected an abnormal (99mTc)MDP bone image increases the probability of the disease, even if the x-rays and CT scans of the spine are normal. An abnormal /sup 67/Ga image following an abnormal 99mTc bone image increases the specificity of the diagnosis. Normal (99mTc)MDP and (/sup 67/Ga)citrate bone images of the vertebra virtually exclude the diagnosis of HPVO.

  3. Streptococcus suis infection

    PubMed Central

    Feng, Youjun; Zhang, Huimin; Wu, Zuowei; Wang, Shihua; Cao, Min; Hu, Dan; Wang, Changjun

    2014-01-01

    Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial strains that represents a primary health problem in the swine industry worldwide. S. suis is also an emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis). Over the past few decades, continued efforts have made significant progress toward better understanding this zoonotic infectious entity, contributing in part to the elucidation of the molecular mechanism underlying its high pathogenicity. This review is aimed at presenting an updated overview of this pathogen from the perspective of molecular epidemiology, clinical diagnosis and typing, virulence mechanism, and protective antigens contributing to its zoonosis. PMID:24667807

  4. An unusual case of Streptococcus anginosus group pyomyositis diagnosed using direct 16S ribosomal DNA sequencing.

    PubMed

    Walkty, Andrew; Embil, John M; Nichol, Kim; Karlowsky, James

    2014-01-01

    Bacteria belonging to the Streptococcus anginosus group (Streptococcus intermedius, Streptococcus constellatus and Streptococcus anginosus) are capable of causing serious pyogenic infections, with a tendency for abscess formation. The present article reports a case of S anginosus group pyomyositis in a 47-year-old man. The pathogen was recovered from one of two blood cultures obtained from the patient, but speciation was initially not performed because the organism was considered to be a contaminant (viridans streptococci group). The diagnosis was ultimately confirmed using 16S ribosomal DNA sequencing of purulent fluid obtained from a muscle abscess aspirate. The present case serves to emphasize that finding even a single positive blood culture of an organism belonging to the S anginosus group should prompt careful evaluation of the patient for a pyogenic focus of infection. It also highlights the potential utility of 16S ribosomal DNA amplification and sequencing in direct pathogen detection from aspirated fluid in cases of pyomyositis in which antimicrobial therapy was initiated before specimen collection. PMID:24634686

  5. Pyogenic splenic abscess in intravenous drug addiction.

    PubMed

    Nallathambi, M N; Ivatury, R R; Lankin, D H; Wapnir, I L; Stahl, W M

    1987-06-01

    Among the surgical complications of intravenous drug addiction, pyogenic splenic abscess is considered to be a rare entity. A review of the literature reveals only 24 cases of splenic abscess secondary to this particular etiology. The authors report five patients with intravenous drug addiction who underwent splenectomy for pyogenic splenic abscess within 1 year. Fever and abdominal pain were the only constant physical signs. Three patients had associated infective endocarditis, and the other two patients sustained blunt trauma to the left side of the trunk weeks earlier. Computed tomography (CT) and ultrasound were diagnostic in all five patients preoperatively, and they were complementary when combined. Four of the five patients had Staphylococcus aureus septicemia at the time of splenectomy. Three patients recovered from their operations, and the other two, both with endocarditis, died postoperatively from causes unrelated to splenic abscess and splenectomy. A high index of suspicion is warranted in this susceptible group of patients with vague abdominal signs and persistent sepsis to rule out splenic suppuration. The noninvasive imaging methods, CT scan and ultrasound, facilitate early diagnosis in these patients. PMID:3579050

  6. Isolation and genotypic characterization of Trueperella (Arcanobacterium) pyogenes recovered from active cranial abscess infections of male white-tailed deer (Odocoileus virginianus).

    PubMed

    Cohen, Bradley S; Belser, Emily H; Keeler, Shamus P; Yabsley, Michael J; Miller, Karl V

    2015-03-01

    Trueperella (Arcanobacterium) pyogenes is a causative agent of suppurative infections in domestic and wild animals. In some populations of captive or free-ranging white-tailed deer (Odocoileus virginianus), cranial abscess disease is an important source of mortality in adult males. Although the pathogenesis of this disease is poorly understood, T. pyogenes has been isolated from active infections with other opportunistic bacteria. In this study, bacteria associated with cranial abscess infections were identified, the prevalence of T. pyogenes associated with these infections was determined, and the presence of known virulence determinants in T. pyogenes isolates was ascertained. Using routine biochemical techniques seven bacterial species were identified from 65 samples taken from active cranial abscess infections of 65 male white-tailed deer. Trueperellapyogenes was recovered from 46 samples; in 32 samples it was the only bacterium species detected. Staphylococcus aureus was detected in 26 samples. From these samples, the presence of known and putative virulence genes of T. pyogenes--plo, nanH, nanP, cbpA, fimA, fimC, fimE, and fimG--was examined by conventional polymerase chain reaction. All T. pyogenes isolates were positive for the pyolysin genes plo, nanP, and fimA. Furthermore, nanH, fimA, fimC, and fimE were detected in over 70% of isolates. Of the isolates tested, 48% had genotypes containing all virulence genes except cbpA. The suggestive virulence potential of all isolates, coupled with the large number of pure cultures obtained, implies that T. pyogenes is a causative agent of cranial abscess disease. PMID:25831577

  7. The majority of 9,729 group A streptococcus strains causing disease secrete SpeB cysteine protease: pathogenesis implications.

    PubMed

    Olsen, Randall J; Raghuram, Anjali; Cantu, Concepcion; Hartman, Meredith H; Jimenez, Francisco E; Lee, Susan; Ngo, Ashley; Rice, Kelsey A; Saddington, Deborah; Spillman, Hannaka; Valson, Chandni; Flores, Anthony R; Beres, Stephen B; Long, S Wesley; Nasser, Waleed; Musser, James M

    2015-12-01

    Group A streptococcus (GAS), the causative agent of pharyngitis and necrotizing fasciitis, secretes the potent cysteine protease SpeB. Several lines of evidence suggest that SpeB is an important virulence factor. SpeB is expressed in human infections, protects mice from lethal challenge when used as a vaccine, and contributes significantly to tissue destruction and dissemination in animal models. However, recent descriptions of mutations in genes implicated in SpeB production have led to the idea that GAS may be under selective pressure to decrease secreted SpeB protease activity during infection. Thus, two divergent hypotheses have been proposed. One postulates that SpeB is a key contributor to pathogenesis; the other, that GAS is under selection to decrease SpeB during infection. In order to distinguish between these alternative hypotheses, we performed casein hydrolysis assays to measure the SpeB protease activity secreted by 6,775 GAS strains recovered from infected humans. The results demonstrated that 84.3% of the strains have a wild-type SpeB protease phenotype. The availability of whole-genome sequence data allowed us to determine the relative frequencies of mutations in genes implicated in SpeB production. The most abundantly mutated genes were direct transcription regulators. We also sequenced the genomes of 2,954 GAS isolates recovered from nonhuman primates with experimental necrotizing fasciitis. No mutations that would result in a SpeB-deficient phenotype were identified. Taken together, these data unambiguously demonstrate that the great majority of GAS strains recovered from infected humans secrete wild-type levels of SpeB protease activity. Our data confirm the important role of SpeB in GAS pathogenesis and help end a long-standing controversy. PMID:26416912

  8. [Streptococcus dysgalactiae subspecies equisimilis bacteremic erythroderma in a pediatric patient: a case report and review of literature].

    PubMed

    Pantoja, Miguel A; Delpiano, Luis; Haquin, Gia

    2014-10-01

    Infections caused by pyogenic streptococci are commons in pediatric ages. However, in the last decades there has been an increase in the isolation of no A or B Streptococci. We report a case of a 6 years old girl, who presents fever for 5 days and erythroderma. Streptococcus dysgalactiae subspecies equisimilis was isolated from blood cultures. She receives antibiotics for 14 days with -lactams with a good clinic evolution with normalization of the inflammatory parameters. This agent -hemoltico presents antigens of Lancefield groups A, C and G, and a great similitude regarding virulence factors, with Streptococcus pyogenes. Frequently in old patients, few reported cases in pediatric population. First line treatment remains -lactam antibiotics for which there are no reports of increasing resistance. PMID:25491463

  9. Group B Streptococcus and Pregnancy

    MedlinePLUS

    ... B Strep and Pregnancy • What is group B streptococcus (GBS)? • What does it mean to be colonized ... planned cesarean birth? •Glossary What is group B streptococcus (GBS)? Group B streptococcus is one of the ...

  10. Capillary hemangioma or pyogenic granuloma: A diagnostic dilemma

    PubMed Central

    Rachappa, M. M.; Triveni, M. N.

    2010-01-01

    Pyogenic granulomas and hemangiomas of oral cavity are well-known benign lesions. Although pyogenic granuloma is known to show a striking predilection for the gingiva and capillary hemangioma for lips, check, and tongue, palatal occurrence of these lesions is extremely rare. The clinical diagnosis of such an uncommon occurrence can be quite challenging as they sometimes may mimic more serious lesions such as malignancies. The purpose of this article is to report an unusual case of benign tumor occurring on hard palate which was clinically diagnosed as pyogenic granuloma and histopathologically as capillary hemangioma. PMID:22114397

  11. Nonsurgical treatment of recurrent gingival pyogenic granuloma: A case report.

    PubMed

    Frumkin, Nathalie; Nashef, Rizan; Shapira, Lior; Wilensky, Asaf

    2015-06-01

    Gingival pyogenic granuloma is a relatively common benign form of mucocutaneous lesion. Although surgical excision is considered to be the standard care, several reports have demonstrated a high recurrence rate of the lesion. In this case report a nonsurgical protocol to treat recurring gingival pyogenic granuloma and prevent further recurrence is suggested. The protocol includes strict oral hygiene instructions, scaling, root planing, and maintenance treatment. To the best of our knowledge, this is the first report of conservative nonsurgical management of recurrent gingival pyogenic granuloma lesions. PMID:25941680

  12. Experimental exposure of young pigs using a pathogenic strain of Streptococcus suis serotype 2 and evaluation of this method for disease prevention.

    PubMed Central

    Torremorell, M; Pijoan, C; Dee, S

    1999-01-01

    Control of Streptococcus suis infections and associated disease have proven to be a difficult challenge under most farm conditions. The objective of this study was to experimentally expose young pigs with a pathogenic strain of S. suis serotype 2 as a means of controlling the disease in a commercial swine farm. Prior to the start of the study, the pathogenic S. suis strain responsible for mortality in the farm was identified and used to experimentally inoculate baby piglets. Over a 3-week period, groups of pigs were selected (100 pigs/wk) and divided into 2 groups: control (50 pigs/week) and experimentally exposed (50 pigs/week). Pigs in the experimentally exposed group were inoculated at 5 d old by tonsillar swabbing with the pathogenic S. suis farm isolate. The effect of exposure with this pathogenic strain was evaluated during the nursery and finishing stages and was based on: morbidity (pigs with central nervous signs (CNS) and/or lameness), mortality and number of treatments required by pigs that had either CNS or lameness. The relative risk (RR) of acquiring disease due to S. suis infection was also calculated. Results showed that morbidity in the experimentally exposed groups was lower than in the control group and these results were statistically different (P = 0.006). Experimentally exposed pigs also showed a statistically significant reduction in lameness problems (P = 0.012), but not in CNS (P = 0.20) or mortality (P = 0.59). Pigs in the control group had an increased RR of 4.76, 8.77 and 2.7 for morbidity, to have lameness or to have CNS signs, respectively. In conclusion, experimental exposure of young pigs with the farm's pathogenic S. suis strain at a young age, had a positive effect in reducing clinical signs characteristics of S. suis infection. This method constitutes a novel approach to the control of S. suis infections in swine farms. Images Figure 1. PMID:10534006

  13. Health Care Associated Hematogenous Pyogenic Vertebral Osteomyelitis

    PubMed Central

    Pigrau, Carlos; Rodríguez-Pardo, Dolors; Fernández-Hidalgo, Nuria; Moretó, Laura; Pellise, Ferran; Larrosa, Maria-Nieves; Puig, Mireia; Almirante, Benito

    2015-01-01

    Abstract Although hematogenous pyogenic spinal infections have been related to hemodialysis (HD), catheter-related sepsis, and sporadically, to other nosocomial infections or procedures, in most recent studies and reviews the impact of nosocomial infection as a risk factor for vertebral osteomyelitis (VO) is not well established. The aim of our study was to describe the risk factors, infectious source, etiology, clinical features, therapy, and outcome of health care associated VO (HCAVO), and compare them with community-acquired VO (CAVO) cases. A retrospective cohort study of consecutive patients with hematogenous VO was conducted in our third-level hospital between 1987 and 2011. HCAVO was defined as onset of symptoms after 1 month of hospitalization or within 6 months after hospital discharge, or ambulatory manipulations in the 6 months before the diagnosis. Over the 25-year study period, among 163 hematogenous pyogenic VO, 41 (25%) were health care associated, a percentage that increased from 15% (9/61) in the 1987–1999 period to 31% (32/102) in the 2000–2011 period (P < 0.01). The presumed source of infection was an intravenous catheter in 14 (34%), cutaneous foci in 8 (20%), urinary tract in 7 (17%), gastrointestinal in 3 (7%), other foci in 3 (7%), and unknown in 6 (15%). Staphylococcus aureus was the most frequently isolated microorganism (14 cases, 34%), followed by coagulase-negative Staphylococci (CoNS) in 6 (15%), and Enterobacteriaceae in 6 (15%) cases. Compared with CAVO cases, patients with HCAVO were older (mean 66.0 SD 13.0 years vs 60.5 SD 15.5 years), had more underlying conditions (73% vs 50%, P < 0.05), neoplasm/immunosuppression (39% vs 7%, P < 0.005), chronic renal failure (19% vs 4%, P < 0.001), a known source of infection (85% vs 54% P < 0.05), Candida spp (7% vs 0%, P < 0.01) or CoNS infections (15% vs 2%, P < 0.05), higher mortality (15% vs 6%, P = 0.069), and a higher relapse rate in survivors (9% vs 1%, P < 0.05). Presently, in our setting, one-third of hematogenous pyogenic VO infections are health care associated, and a third of these are potentially preventable catheter-related infections. Compared with CAVO, in health care associated hematogenous VO, mortality and relapse rates are higher; hence, further prevention measures should be assessed. PMID:25621677

  14. 77 FR 26014 - Prospective Grant of Exclusive License: P4 Peptide From Streptococcus Pneumoniae

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... Peptide From Streptococcus Pneumoniae AGENCY: Technology Transfer Office, Centers for Disease Control and... prevention of Streptococcus pneumonia infection in humans'') to practice the inventions embodied in the... of Streptococcus Pneumoniae PsaA Antigen and Uses Thereof,'' filed 7/ 18/2008, claiming priority to...

  15. Pyomyositis due to Streptococcus pneumoniae.

    PubMed

    Wong, S Lindsey; Anthony, Evelyn Y; Shetty, Avinash K

    2009-06-01

    Pyomyositis is an unusual but potentially serious disease in children. Staphylococcus aureus is the most commonly implicated pathogen, but pneumococcal pyomyositis is very rare. Clinical diagnosis of pyomyositis can be difficult often mimicking septic arthritis of the hip or appendicitis. We report a 12-year-old male with pyomyositis caused by Streptococcus pneumoniae who presented with fever and severe right hip and abdominal pain. Magnetic resonance imaging of the right hip revealed the diagnosis of pyomyositis. Blood cultures grew Streptococcus pneumoniae, sensitive to penicillin, ceftriaxone, and clindamycin. He was successfully treated with a 3-week course of clindamycin. Early recognition, appropriate antibiotic therapy, and if indicated, drainage of the muscle abscess is critical to reduce morbidity and mortality. PMID:19497488

  16. Human Streptococcus agalactiae isolate in Nile tilapia (Oreochromis niloticus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus agalactiae, the Lancefield group B Streptococcus (GBS), long recognized as a mammalian pathogen, is an emerging pathogen to fish. We show that a GBS serotype Ia, multilocus sequence type ST-7 isolate from a human neonatal meningitis clinical case causes disease signs and mortality in N...

  17. Three cases of Arcanobacterium pyogenes-associated soft tissue infection.

    PubMed

    Kavitha, Kannaiyan; Latha, R; Udayashankar, C; Jayanthi, K; Oudeacoumar, P

    2010-06-01

    Arcanobacterium pyogenes is an established but often unrecognized human pathogen. A. pyogenes may also be misidentified as Arcanobacterium haemolyticum, which gives remarkably similar results in conventional biochemical tests. In this study, we have reported three cases of wound infections associated with A. pyogenes and also on the bacteriological characteristics which are relevant for identification of these isolates. The negative reverse CAMP test, the ability to produce acid from xylose and to hydrolyse gelatin and the positive beta-glucuronidase test clearly differentiated A. pyogenes from other closely related species. All three isolates were uniformly susceptible to penicillin, ampicillin, amoxicillin-clavulanic acid, ceftriaxone and gentamicin, variably susceptible to tetracycline and erythromycin and uniformly resistant to cotrimoxazole. Only a few confirmed cases have been reported throughout the world and therefore the diagnostic evaluation of this organism is emphasized. PMID:20299502

  18. Pyogenic granuloma on the upper labial mucosa: a case report.

    PubMed

    K A, Kamala; Ashok, L; G P, Sujatha

    2013-06-01

    Pyogenic granuloma is thought to represent an exuberant tissue response to a local irritation or trauma. It is a reactional response to constant minor trauma and it might be related to hormonal changes. Clinically, these lesions usually present as single nodules or sessile papules with smooth or lobulated surfaces. These may be seen in any size, from a few millimetres to several centimetres. Pyogenic granuloma of the oral cavity is known to involve the gingiva more commonly (75% of all the cases). An extragingival occurrence of pyogenic granuloma is rare. This paper has described an extragingival pyogenic granuloma which occurred on the upper labial mucosa in a 30 years old female patient. PMID:23905151

  19. Pyogenic Granuloma on the Upper Labial Mucosa: A Case Report

    PubMed Central

    K A, Kamala; Ashok, L.; G P, Sujatha

    2013-01-01

    Pyogenic granuloma is thought to represent an exuberant tissue response to a local irritation or trauma. It is a reactional response to constant minor trauma and it might be related to hormonal changes. Clinically, these lesions usually present as single nodules or sessile papules with smooth or lobulated surfaces. These may be seen in any size, from a few millimetres to several centimetres. Pyogenic granuloma of the oral cavity is known to involve the gingiva more commonly (75% of all the cases). An extragingival occurrence of pyogenic granuloma is rare. This paper has described an extragingival pyogenic granuloma which occurred on the upper labial mucosa in a 30 years old female patient. PMID:23905151

  20. Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China.

    PubMed

    Zhou, X; Liu, J; Zhang, Z; Liu, Y; Wang, Y; Liu, Y

    2016-04-01

    Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p < 0.01). The patterns of amino acid mutation in PBP2b, PBP2x and PBP1a were unique and different from those of other countries. All of the serotype 19A and 19F PRSP isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China. PMID:26972430

  1. Bactericidal effect of extracts and metabolites of Robinia pseudoacacia L. on Streptococcus mutans and Porphyromonas gingivalis causing dental plaque and periodontal inflammatory diseases.

    PubMed

    Patra, Jayanta Kumar; Kim, Eun Sil; Oh, Kyounghee; Kim, Hyeon-Jeong; Dhakal, Radhika; Kim, Yangseon; Baek, Kwang-Hyun

    2015-01-01

    The mouth cavity hosts many types of anaerobic bacteria, including Streptococcus mutans and Porphyromonas gingivalis, which cause periodontal inflammatory diseases and dental caries. The present study was conducted to evaluate the antibacterial potential of extracts of Robinia pseudoacacia and its different fractions, as well as some of its natural compounds against oral pathogens and a nonpathogenic reference bacteria, Escherichia coli. The antibacterial activity of the crude extract and the solvent fractions (hexane, chloroform, ethyl acetate and butanol) of R. pseudoacacia were evaluated against S. mutans, P. gingivalis and E. coli DH5? by standard micro-assay procedure using conventional sterile polystyrene microplates. The results showed that the crude extract was more active against P. gingivalis (100% growth inhibition) than against S. mutans (73% growth inhibition) at 1.8 mg/mL. The chloroform and hexane fractions were active against P. gingivalis, with 91 and 97% growth inhibition, respectively, at 0.2 mg/mL. None of seven natural compounds found in R. pseudoacacia exerted an antibacterial effect on P. gingivalis; however, fisetin and myricetin at 8 g/mL inhibited the growth of S. mutans by 81% and 86%, respectively. The crude extract of R. pseudoacacia possesses bioactive compounds that could completely control the growth of P. gingivalis. The antibiotic activities of the hexane and chloroform fractions suggest that the active compounds are hydrophobic in nature. The results indicate the effectiveness of the plant in clinical applications for the treatment of dental plaque and periodontal inflammatory diseases and its potential use as disinfectant for various surgical and orthodontic appliances. PMID:25856062

  2. Pyogenic granuloma of the cornea induced by "snake oil".

    PubMed

    Proia, A D; Small, K W

    1994-05-01

    A pyogenic granuloma of the cornea developed on the vascularized cornea of a 79-year-old woman after "snake oil" accidentally dripped in her eye. The snake oil was being used to relieve forehead pain, which may have been referred. The five previously reported examples of corneal pyogenic granuloma are similar to this case in that trauma preceded development of the lesion. However, the chemical trauma induced by the snake oil appears to be a unique mechanism of injury. PMID:8033584

  3. Streptococcus suis infection.

    PubMed

    Huang, Yu-Tsung; Teng, Lee-Jene; Ho, Shen-Wu; Hsueh, Po-Ren

    2005-10-01

    A recent outbreak of Streptococcus suis infection associated with the slaughter, preparation or consumption of pigs in Sichuan, China has led to concerns that similar outbreaks could occur in other Asian countries. Although the pig farming industry is flourishing in Taiwan, reports of S. suis infection remain rare. We report 2 cases of S. suis meningitis successfully treated with ceftriaxone and penicillin. Previous reports of S. suis infection from the English literature are reviewed and the clinical data of cases reported in Asian and European countries are summarized. In Europe, there was good correlation between clinical disease and porcine contact, while few cases in Asia reported this association. Meningitis remained the most common presentation of infection in both areas (84.6% and 75.2%, respectively), followed by sepsis (15.4% and 18.6%, respectively), which had a higher mortality rate, particularly for splenectomized patients. Other clinical presentations included enteritis, arthritis, endocarditis, pneumonia, spondylodiscitis, endophthalmitis, uveitis and peritonitis. Deafness was a distinct sequelae (50.5% in Europe and 51.9% in Asia) after recovery from S. suis infection, especially in patients with meningitis. Not all commercial identification systems for streptococci could offer adequate speciation for S. suis. When viridans group streptococci are isolated from patients with meningitis and sepsis, prompt and correct identification of isolates to the species level should be performed, especially in areas with a high prevalence of S. suis diseases. PMID:16211137

  4. CSF Proteins as Discreminatory Markers of Tubercular and Pyogenic Meningitis

    PubMed Central

    Shekhar, Ravi; Rao, J. Rama; Devi, K. Ambika; Rao, R Babu

    2013-01-01

    Introduction: Meningitis is still a major cause of illness in many parts of the world. Though substantial improvement has been occurred in the diagnosis of meningitis, conclusive differentiation between tubercular and pyogenic meningitis remains to be an unsolved problem. Patients with meningitis often have severe neurological deficit or die inspite of antibiotic therapy. Thus, improvement in diagnostic test and therapy is required. The objective of the present study was to find a simple biochemical marker for diagnosis of meningitis and differentiation of tubercular and pyogenic meningitis. Materials and Methods: CSF samples were collected from 90 paediatric patients from Nilofer Hospital, Hyderabad, India, from age group of 4 months to 12 years. CSF samples were collected by performing Lumbar Puncture under aseptic conditions and with required precaution. CSF samples were divided into 3 groups where Group 1 included Control that was without CSF inflammation, Group 2 with Tuberculous Meningitis & Group 3 consisting of Pyogenic Meningitis with 30 samples in each group. Electrophoretic analysis of CSF proteins was performed which separated as bands of pre-albumin, albumin, alpha, beta and gamma globulins. Result: Protein content in CSF was 259 409 mg/dl in tuberculous meningitis, whereas in pyogenic meningitis it was 111 83.94 mg/dl and in control group was 19 13.3 mg/dl. Electrophoretic analysis revealed pre-albumin band to be 2.8 1.2 % in tuberculous meningitis, which was significantly decreased when compared with control and pyogenic meningitis. Albumin band in tuberculous meningitis was 34.8 9.9 %, which was also significantly decreased when compared to control and pyogenic meningitis. Alpha band was 19.7 6.9 % in pyogenic meningitis, but in control and tubeculous meningitis it was 10.4 2.9% and 10.3 5.2% respectively. Beta band was found similar in all the three groups. Gamma band was 33.2 8.08% in tuberculous meningitis, 13.8 4.55% in control and 16.7 13.18% in pyogenic meningitis. Conclusion: Pre-albumin band was found to be decreased and gamma band was shown to be increased in tuberculous meningitis. Alpha band was increased in pyogenic meningitis. Thus, CSF protein fraction separated and quantitated by native Polyacrylamide slab gel electrophoresis, could be used as markers in differentiation of tubercular and pyogenic meningitis. PMID:24086846

  5. Dietary supplementation with Bacillus subtilis, Saccharomyces cerevisiae and Aspergillus oryzae enhance immunity and disease resistance against Aeromonas hydrophila and Streptococcus iniae infection in juvenile tilapia Oreochromis niloticus.

    PubMed

    Iwashita, Marina Keiko P; Nakandakare, Ivan B; Terhune, Jeffery S; Wood, Theresa; Ranzani-Paiva, Maria Jos T

    2015-03-01

    A feeding trial was conducted to investigate the effects of dietary administration of probiotic with Bacillus subtilis, Aspergillus oryzae and Saccharomyces cerevisiae on growth, innate immune response, Hemato-immunological parameters and disease resistance of Nile tilapia, Oreochromis niloticus. Animals were distributed in three equal groups, each of five replicates and received one of the following experimental diets for four weeks: Control, non-supplemented diet; 5 g kg(-1) probiotic mixture (B. subtilis 1.5 10(9) CFU g(-1), S. cerevisiae 10(9) CFU g(-1) and A. oryzae 2 10(9) CFU g(-1)); and 10 g kg(-1) probiotic mixture (B. subtilis 3.0 10(9) CFU g(-1), S. cerevisiae 2.0 10(9) CFU g(-1) and A. oryzae 4.0 10(9) CFU g(-1)). The respiratory burst activity, white blood cells and hematological parameters were evaluated after four, five and six weeks of feeding. At the end of the growth trial, fish were sampled for intestinal microbiology and challenged by intraperitoneal injection of LD50 concentration of Aeromonas hydrophila and Streptococcus iniae. Mortality was recorded for the following 3 weeks. Results showed that administration of the probiotic had no significant effect on the growth rates of Nile tilapias, although the fish fed probiotics had better feed conversion. Respiratory burst activity, erythrocyte fragility and levels of white blood cells were significantly improved in tilapias fed diet supplemented with probiotic levels (P < 0.05), which may exhibit up-regulating effects on tilapia immune parameters. The cumulative mortality after A. hydrophila and S. iniae challenge decreased in tilapias fed with probiotic (P < 0.05). The present study demonstrated the potential of B. subtilis, S. cerevisiae and A. oryzae combined as beneficial dietary probiotic in juvenile O. niloticus. PMID:25530581

  6. PHAGOCYTIC IMMUNITY IN STREPTOCOCCUS INFECTIONS.

    PubMed

    Meakins, J C

    1909-11-01

    1. In infections with streptococcus in man, such as acute septic endocarditis, and tonsillitis, there is produced a powerful opsonic immunity. 2. This opsonic immunity is effective towards the streptococcus which has caused infection but may be ineffective in the presence of streptococcus from other sources. 3. Little benefit can be expected from streptococcus vaccines unless they are prepared from the streptococcus which has caused infection. PMID:19867288

  7. A Second Tylosin Resistance Determinant, Erm B, in Arcanobacterium pyogenes

    PubMed Central

    Jost, B. Helen; Trinh, Hien T.; Songer, J. Glenn; Billington, Stephen J.

    2004-01-01

    Arcanobacterium pyogenes, a common inhabitant of the mucosal surfaces of livestock, is also a pathogen associated with a variety of infections. In livestock, A. pyogenes is exposed to antimicrobial agents used for prophylaxis and therapy, notably tylosin, a macrolide used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Many, but not all, tylosin-resistant A. pyogenes isolates carry erm(X), suggesting the presence of other determinants of tylosin resistance. Oligonucleotide primers designed for conserved regions of erm(B), erm(C), and erm(T) were used to amplify a 404-bp fragment from a tylosin-resistant A. pyogenes isolate, OX-7. DNA sequencing revealed that the PCR product was 100% identical to erm(B) genes, and the erm(B) gene region was cloned in Escherichia coli. The A. pyogenes Erm B determinant had the most DNA identity with an Erm B determinant carried by the Clostridium perfringens plasmid pIP402. However, the A. pyogenes determinant lacked direct repeat DR1 and contained a deletion in DR2. Flanking the A. pyogenes erm(B) gene were partial and entire genes similar to those found on the Enterococcus faecalis multiresistance plasmid pRE25. This novel architecture suggests that the erm(B) element may have arisen by recombination of two distinct genetic elements. Ten of 32 tylosin-resistant isolates carried erm(B), as determined by DNA hybridization, and all 10 isolates carried a similar element. Insertion of the element was site specific, as PCR and Southern blotting analysis revealed that the erm(B) element was inserted into orfY, a gene of unknown function. However, in three strains, this insertion resulted in a partial duplication of orfY. PMID:14982756

  8. A second tylosin resistance determinant, Erm B, in Arcanobacterium pyogenes.

    PubMed

    Jost, B Helen; Trinh, Hien T; Songer, J Glenn; Billington, Stephen J

    2004-03-01

    Arcanobacterium pyogenes, a common inhabitant of the mucosal surfaces of livestock, is also a pathogen associated with a variety of infections. In livestock, A. pyogenes is exposed to antimicrobial agents used for prophylaxis and therapy, notably tylosin, a macrolide used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Many, but not all, tylosin-resistant A. pyogenes isolates carry erm(X), suggesting the presence of other determinants of tylosin resistance. Oligonucleotide primers designed for conserved regions of erm(B), erm(C), and erm(T) were used to amplify a 404-bp fragment from a tylosin-resistant A. pyogenes isolate, OX-7. DNA sequencing revealed that the PCR product was 100% identical to erm(B) genes, and the erm(B) gene region was cloned in Escherichia coli. The A. pyogenes Erm B determinant had the most DNA identity with an Erm B determinant carried by the Clostridium perfringens plasmid pIP402. However, the A. pyogenes determinant lacked direct repeat DR1 and contained a deletion in DR2. Flanking the A. pyogenes erm(B) gene were partial and entire genes similar to those found on the Enterococcus faecalis multiresistance plasmid pRE25. This novel architecture suggests that the erm(B) element may have arisen by recombination of two distinct genetic elements. Ten of 32 tylosin-resistant isolates carried erm(B), as determined by DNA hybridization, and all 10 isolates carried a similar element. Insertion of the element was site specific, as PCR and Southern blotting analysis revealed that the erm(B) element was inserted into orfY, a gene of unknown function. However, in three strains, this insertion resulted in a partial duplication of orfY. PMID:14982756

  9. Protein Array Profiling of Tic Patient Sera Reveals a Broad Range and Enhanced Immune Response against Group A Streptococcus Antigens

    PubMed Central

    Bombaci, Mauro; Grifantini, Renata; Mora, Marirosa; Reguzzi, Valerio; Petracca, Roberto; Meoni, Eva; Balloni, Sergio; Zingaretti, Chiara; Falugi, Fabiana; Manetti, Andrea G. O.; Margarit, Immaculada; Musser, James M.; Cardona, Francesco; Orefici, Graziella; Grandi, Guido; Bensi, Giuliano

    2009-01-01

    The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen-dependent induction of autoantibodies in susceptible individuals may be involved the occurrence of tic disorders. PMID:19623252

  10. SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion

    PubMed Central

    Gallotta, Marilena; Gancitano, Giovanni; Pietrocola, Giampiero; Mora, Marirosa; Pezzicoli, Alfredo; Tuscano, Giovanna; Chiarot, Emiliano; Nardi-Dei, Vincenzo; Taddei, Anna Rita; Rindi, Simonetta; Speziale, Pietro; Soriani, Marco; Bensi, Giuliano

    2014-01-01

    Group A streptococcus (GAS) is a human pathogen causing a wide repertoire of mild and severe diseases for which no vaccine is yet available. We recently reported the identification of three protein antigens that in combination conferred wide protection against GAS infection in mice. Here we focused our attention on the characterization of one of these three antigens, Spy0269, a highly conserved, surface-exposed, and immunogenic protein of unknown function. Deletion of the spy0269 gene in a GAS M1 isolate resulted in very long bacterial chains, which is indicative of an impaired capacity of the knockout mutant to properly divide. Confocal microscopy and immunoprecipitation experiments demonstrated that the protein was mainly localized at the cell septum and could interact in vitro with the cell division protein FtsZ, leading us to hypothesize that Spy0269 is a member of the GAS divisome machinery. Predicted structural domains and sequence homologies with known streptococcal adhesins suggested that this antigen could also play a role in mediating GAS interaction with host cells. This hypothesis was confirmed by showing that recombinant Spy0269 could bind to mammalian epithelial cells in vitro and that Lactococcus lactis expressing Spy0269 on its cell surface could adhere to mammalian cells in vitro and to mice nasal mucosa in vivo. On the basis of these data, we believe that Spy0269 is involved both in bacterial cell division and in adhesion to host cells and we propose to rename this multifunctional moonlighting protein as SpyAD (Streptococcus pyogenes Adhesion and Division protein). PMID:24778116

  11. Streptolysin S Promotes Programmed Cell Death and Enhances Inflammatory Signaling in Epithelial Keratinocytes during Group A Streptococcus Infection.

    PubMed

    Flaherty, Rebecca A; Puricelli, Jessica M; Higashi, Dustin L; Park, Claudia J; Lee, Shaun W

    2015-10-01

    Streptococcus pyogenes, or group A Streptococcus (GAS), is a pathogen that causes a multitude of human diseases from pharyngitis to severe infections such as toxic shock syndrome and necrotizing fasciitis. One of the primary virulence factors produced by GAS is the peptide toxin streptolysin S (SLS). In addition to its well-recognized role as a cytolysin, recent evidence has indicated that SLS may influence host cell signaling pathways at sublytic concentrations during infection. We employed an antibody array-based approach to comprehensively identify global host cell changes in human epithelial keratinocytes in response to the SLS toxin. We identified key SLS-dependent host responses, including the initiation of specific programmed cell death and inflammatory cascades with concomitant downregulation of Akt-mediated cytoprotection. Significant signaling responses identified by our array analysis were confirmed using biochemical and protein identification methods. To further demonstrate that the observed SLS-dependent host signaling changes were mediated primarily by the secreted toxin, we designed a Transwell infection system in which direct bacterial attachment to host cells was prevented, while secreted factors were allowed access to host cells. The results using this approach were consistent with our direct infection studies and reveal that SLS is a bacterial toxin that does not require bacterial attachment to host cells for activity. In light of these findings, we propose that the production of SLS by GAS during skin infection promotes invasive outcomes by triggering programmed cell death and inflammatory cascades in host cells to breach the keratinocyte barrier for dissemination into deeper tissues. PMID:26238711

  12. Serotypes and Clonal Diversity of Streptococcus pneumoniae Causing Invasive Disease in the Era of PCV13 in Catalonia, Spain

    PubMed Central

    del Amo, Eva; Esteva, Cristina; Hernandez-Bou, Susanna; Galles, Carmen; Navarro, Marian; Sauca, Goretti; Diaz, Alvaro; Gassiot, Paula; Marti, Carmina; Larrosa, Nieves; Ciruela, Pilar; Jane, Mireia; Sá-Leão, Raquel; Muñoz-Almagro, Carmen

    2016-01-01

    The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination. PMID:26953887

  13. Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization

    PubMed Central

    Patras, Kathryn A.; Wescombe, Philip A.; Rösler, Berenice; Hale, John D.; Tagg, John R.

    2015-01-01

    Streptococcus agalactiae (group B streptococcus [GBS]) colonizes the rectovaginal tract in 20% to 30% of women and during pregnancy can be transmitted to the newborn, causing severe invasive disease. Current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission, and GBS remains a leading cause of neonatal infection. We have investigated the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Comparison of the antibacterial activities of multiple S. salivarius strains by use of a deferred-antagonism test showed that S. salivarius strain K12 exhibited the broadest spectrum of activity against GBS. K12 effectively inhibited all GBS strains tested, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. Inhibition was dependent on the presence of megaplasmid pSsal-K12, which encodes the bacteriocins salivaricin A and salivaricin B; however, in coculture experiments, GBS growth was impeded by K12 independently of the megaplasmid. We also demonstrated that K12 adheres to and invades human vaginal epithelial cells at levels comparable to GBS. Inhibitory activity of K12 was examined in vivo using a mouse model of GBS vaginal colonization. Mice colonized with GBS were treated vaginally with K12. K12 administration significantly reduced GBS vaginal colonization in comparison to nontreated controls, and this effect was partially dependent on the K12 megaplasmid. Our results suggest that K12 may have potential as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy. PMID:26077762

  14. Streptococcus salivarius K12 Limits Group B Streptococcus Vaginal Colonization.

    PubMed

    Patras, Kathryn A; Wescombe, Philip A; Rösler, Berenice; Hale, John D; Tagg, John R; Doran, Kelly S

    2015-09-01

    Streptococcus agalactiae (group B streptococcus [GBS]) colonizes the rectovaginal tract in 20% to 30% of women and during pregnancy can be transmitted to the newborn, causing severe invasive disease. Current routine screening and antibiotic prophylaxis have fallen short of complete prevention of GBS transmission, and GBS remains a leading cause of neonatal infection. We have investigated the ability of Streptococcus salivarius, a predominant member of the native human oral microbiota, to control GBS colonization. Comparison of the antibacterial activities of multiple S. salivarius strains by use of a deferred-antagonism test showed that S. salivarius strain K12 exhibited the broadest spectrum of activity against GBS. K12 effectively inhibited all GBS strains tested, including disease-implicated isolates from newborns and colonizing isolates from the vaginal tract of pregnant women. Inhibition was dependent on the presence of megaplasmid pSsal-K12, which encodes the bacteriocins salivaricin A and salivaricin B; however, in coculture experiments, GBS growth was impeded by K12 independently of the megaplasmid. We also demonstrated that K12 adheres to and invades human vaginal epithelial cells at levels comparable to GBS. Inhibitory activity of K12 was examined in vivo using a mouse model of GBS vaginal colonization. Mice colonized with GBS were treated vaginally with K12. K12 administration significantly reduced GBS vaginal colonization in comparison to nontreated controls, and this effect was partially dependent on the K12 megaplasmid. Our results suggest that K12 may have potential as a preventative therapy to control GBS vaginal colonization and thereby prevent its transmission to the neonate during pregnancy. PMID:26077762

  15. Diversity of Pneumolysin and Pneumococcal Histidine Triad Protein D of Streptococcus pneumoniae Isolated from Invasive Diseases in Korean Children

    PubMed Central

    Yun, Ki Wook; Lee, Hyunju; Choi, Eun Hwa; Lee, Hoan Jong

    2015-01-01

    Pneumolysin (Ply) and pneumococcal histidine triad protein D (PhtD) are candidate proteins for a next-generation pneumococcal vaccine. We aimed to analyze the genetic diversity and antigenic heterogeneity of Ply and PhtD for 173 pneumococci isolated from invasive diseases in Korean children. Allele was designated based on the variation of amino acid sequence. Antigenicity was predicted by the amino acid hydrophobicity of the region. There were seven and 39 allele types for the ply and phtD genes, respectively. The nucleotide sequence identity was 97.2%-99.9% for ply and 91.4%-98.0% for phtD gene. Only minor variations in hydrophobicity were noted among the antigenicity plots of Ply and PhtD. Overall, the allele types of the ply and phtD genes were remarkably homogeneous, and the antigenic diversity of the corresponding proteins was very limited. The Ply and PhtD could be useful antigens for universal pneumococcal vaccines. PMID:26252211

  16. Multiple Eruptive Pyogenic Granulomas Occurring in a Region of Scalded Skin.

    PubMed

    Xu, Yu; Li, Hui; Wang, Zai-Xing; Yang, Sen

    2016-01-01

    We report a case of multiple eruptive pyogenic granulomas after scalding. A 4-year-old girl developed papules and nodules within the scalded areas after a hot soup burn. Although the occurrence of pyogenic granulomas after trauma to the skin is common, multiple lesions of pyogenic granuloma secondary to scalding are rare. PMID:26572497

  17. Changing trends in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive diseases in Central Thailand, 20092012

    PubMed Central

    Phongsamart, Wanatpreeya; Srifeungfung, Somporn; Chatsuwan, Tanittha; Nunthapisud, Pongpun; Treerauthaweeraphong, Vipa; Rungnobhakhun, Pimpha; Sricharoenchai, Sirintip; Chokephaibulkit, Kulkanya

    2014-01-01

    To describe the trends in serotype distribution and antimicrobial susceptibility of S. pneumoniae causing invasive pneumococcal diseases (IPD) we tested 238 pneumococci isolates from normally sterile sites between 2009 and 2012 and compared these findings with previous data collected within our network. Serotyping was performed for 15 serotypes contained in the 7-,10-, 13-, and experimental 15-valent pneumococcal conjugate vaccines (PCV). The most common serotypes found were 6B (13.9%), 19A (12.6%), 14 (8.0%), 18C (5.9%), and 6A (3.8%); and 39.9% were non-PCV15 serotypes. One of 81 patients with available data had breakthrough infection with vaccine serotype (19F). There was a significant increase of serotype 19A among children ?5 years (5.6% in 20002009 vs 18.3% in 20092012, P = 0.003). The all-age serotype coverage was 36.4%, 41.5%, 59.3%, and 59.7% for PCV7, PCV10, PCV13, and PCV 15, respectively. The corresponding coverage in children ?5 years were 46.4%, 48.8%, 73.2%, and 73.2% respectively. High susceptibilities to penicillin (89.7%), cefotaxime (95.7%), cefditoren (90.2% by Spanish breakpoints), ofloxacin (97.9%), and levofloxacin (100%), but low to cefdinir (50.0%), cefditoren (45.1% by US-FDA breakpoints), macrolides (<50%), clindamycin (67.7%), tetracycline (41.4%), and trimethoprim-sulfamethoxazole (32.4%) were observed. Serotype 19A was less susceptible to penicillin (80.0 vs 91.2%, P = 0.046), cefditoren (66.7 vs 95.5% by Spanish breakpoints, P = 0.004), and tetracycline (9.1 vs 45.5%, P = 0.024) than non-19A isolates. These data emphasize the need for continued surveillance to monitor changes in serotypes as well as antimicrobial susceptibilities in order to guide strategies for prevention and treatment. PMID:25424794

  18. Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease.

    PubMed Central

    Burns, E H; Marciel, A M; Musser, J M

    1996-01-01

    Human umbilical vein endothelial cells (HUVECs) were used to gain insight into the molecular mechanism whereby the major extracellular protease from group A streptococci damages host tissue. HUVECs exposed to streptococcal cysteine protease (SCP) for various times exhibited cytopathic effect and cell detachment from the culture vessel. Gelatin substrate zymography showed that a time- and concentration-dependent increase in the level of activity of an approximately 66-kDa gelatinase occurred in culture medium taken from cells exposed to enzymatically active SCP. This gelatinase comigrated in gelatin zymograms with the activated form of purified recombinant matrix metalloprotease 2 (MMP-2) and had type IV collagenase activity. In contrast, medium taken from cells exposed to inactivated (boiled) SCP and cells exposed to SCP inhibited by treatment with N-benzyloxycarbonyl-leucyl-valyl-glycine diazomethyl ketone lacked the 66-kDa gelatinase. Appearance of the 66-kDa gelatinase activity was also prevented by 1,10-phenanthroline, a zinc chelator and MMP inhibitor. Inasmuch as proteolytically active SCP is required for the emergence of this gelatinase and MMP activation occurs by proteolytic processing, the 66-kDa gelatinase may be a proteolytic cleavage product of a latent MMP expressed extracellularly by HUVECs. Direct SCP treatment of culture supernatant taken from HUVECs not exposed to SCP also produced the 66-kDa gelatinase. The data show that SCP activates an MMP produced by human endothelial cells, a process that may contribute to endothelial cell damage, tissue destruction, and hemodynamic derangement observed in some patients with severe, invasive group A streptococcal infection. PMID:8890235

  19. Characterization of Isolates of Streptococcus agalactiae from Diseased Farmed and Wild Marine Fish from the U.S. Gulf Coast, Latin America, and Thailand.

    PubMed

    Soto, Esteban; Wang, Rui; Wiles, Judy; Baumgartner, Wes; Green, Christopher; Plumb, John; Hawke, John

    2015-06-01

    We examined Lancefield serogroup B Streptococcus isolates recovered from diseased, cultured hybrid Striped Bass (Striped Bass Morone saxatilis × White Bass M. chrysops) and wild and cultured Gulf Killifish Fundulus grandis from coastal waters of the U.S. Gulf of Mexico (Gulf coast) and compared those isolates to strains from tilapias Oreochromis spp. reared in Mississippi, Thailand, Ecuador, and Honduras and to the original Gulf coast strain identified by Plumb et al. ( 1974 ). The isolates were subjected to phylogenetic, biochemical, and antibiotic susceptibility analyses. Genetic analysis was performed using partial sequence comparison of (1) the 16S ribosomal RNA (rRNA) gene; (2) the sipA gene, which encodes a surface immunogenic protein; (3) the cspA gene, which encodes a cell surface-associated protein; and (4) the secY gene, which encodes components of a general protein secretion pathway. Phylogenies inferred from sipA, secY, and cspA gene sequence comparisons were more discriminating than that inferred from the 16S rRNA gene sequence comparison. The U.S. Gulf coast strains showed a high degree of similarity to strains from South America and Central America and belonged to a unique group that can be distinguished from other group B streptococci. In agreement with the molecular findings, biochemical and antimicrobial resistance analyses demonstrated that the isolates recovered from the U.S. Gulf coast and Latin America were more similar to each other than to isolates from Thailand. Three laboratory challenge methods for inducing streptococcosis in Gulf Killifish were evaluated-intraperitoneal (IP) injection, immersion (IMM), and immersion plus abrasion (IMMA)-using serial dilutions of S. agalactiae isolate LADL 97-151, a representative U.S. Gulf coast strain. The dose that was lethal to 50% of test fish by 14 d postchallenge was approximately 2 CFU/fish via IP injection. In contrast, the fish that were challenged via IMM or IMMA presented cumulative mortality less than 40% by 14 d postchallenge. PMID:26030196

  20. Dietary Aloe vera supplementation on growth performance, some haemato-biochemical parameters and disease resistance against Streptococcus iniae in tilapia (GIFT).

    PubMed

    Gabriel, Ndakalimwe Naftal; Qiang, Jun; He, Jie; Ma, Xin Yu; Kpundeh, Mathew D; Xu, Pao

    2015-06-01

    This study investigated effects of dietary Aloe vera on growth performance, some haemato-biochemical parameters and disease resistance against Streptococcus iniae in tilapia (GIFT). Five groups were designed including a basal diet (control) and 100% A. vera powder incorporated in fish feed at 0.5% 1%, 2%, and 4%/kg feed, which were administered for 8 weeks. Fish fed 0.5%, 1%, and 2% A. vera supplemented diet significantly improved (p < 0.05) weight gain, absolute growth rate and specific growth rate. Feed intake significantly increased in fish fed with A. vera diet at 1% and 2%/kg feed. Feed efficiency ratio, feed conversion ratio, and hepatosomatic index were significantly enhanced in 4% A. vera supplemented fish over unsupplemented ones (p < 0.05). Several haemato-biochemical indices were examined before and after fish were challenged with S. iniae pathogen containing 7.7 × 10(6) CFU cells mL(-1). A. vera supplemented fish showed a significant increase (p < 0.05) in red blood cells, hematocrits (Hb), hemoglobin (Hb), white blood cells (WBC), neutrophils, monocytes, eosinophils, serum total protein, glucose and cortisol after challenge when compared to unsupplemented ones. Meanwhile, 4% A. vera supplemented fish showed a decrease (p < 0.05) in RBC, Hb, Ht, WBC, and mean corpuscular hemoglobin (MCH) after challenge compared to unsupplemented ones and other supplemented ones. In addition, lower mean corpuscular volume values (MCV) (p < 0.05) were observed in fish fed with A. vera diet at 2% and 4% A. vera/kg feed than those fed unsupplemented diet. Unchallenged fish fed 0.5%, 1%, and 2% A. vera showed significantly higher values (p < 0.05) of mean corpuscular hemoglobin concentration (MCHC) than those fed unsupplemented diet and 4% A. vera supplemented diet. There was a significant increase (p < 0.05) in the neutrophil to lymphocyte ratio (N/L) within experimental groups after challenge; N/L ratio in A. vera unsupplemented fish and those supplemented with A. vera diet at 1%/kg feed increased significantly (p < 0.05) throughout challenge period; while those fed 4% A. vera supplemented diet maintained higher values at all experimental stages among groups. There was a significant correlation (p < 0.05, r = 0.53) between N/L ratio and glucose concentration, 96 h after challenge. Aloe had no significant effect (p > 0.05) on the survival of the fish when compared to the control; no mortality was recorded in challenge trial. Overall, our results indicated that dietary aloe supplementation could improve growth, feed utilization, and haemato-biochemical parameters of cultured tilapia. PMID:25758848

  1. Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence.

    PubMed

    King, S J; Heath, P J; Luque, I; Tarradas, C; Dowson, C G; Whatmore, A M

    2001-12-01

    Streptococcus suis is an economically important pathogen of pigs responsible for a variety of diseases including meningitis, septicemia, arthritis, and pneumonia, although little is known about the mechanisms of pathogenesis or virulence factors associated with this organism. Here, we report on the distribution and genetic diversity of the putative virulence factor suilysin, a member of the thiol-activated toxin family of gram-positive bacteria. On the basis of PCR analysis of over 300 isolates of S. suis, the suilysin-encoding gene, sly, was detected in 69.4% of isolates. However, sly was present in a considerably higher proportion of isolates obtained from cases of meningitis, septicemia, and arthritis (>80%) and isolates obtained from asymptomatic tonsillar carriage (>90%) than lung isolates associated with pneumonia (44%). With the exception of serotypes 1, 14, and 1/14, there was no strong correlation between the presence of suilysin and serotype. Analysis of the genetic diversity of suilysin by restriction fragment length polymorphism and sequence analysis found that the suilysin gene, where present, is highly conserved with a maximum of 1.79% diversity at the nucleotide level seen between sly alleles. Assays of hemolytic activity and hybridization analysis provided no evidence for a second member of the thiol-activated toxin family in S. suis. Inverse PCR was used to characterize regions flanking sly, which in turn allowed the first characterization of the equivalent region in a strain lacking sly. Sequence comparison of these regions from sly-positive (P1/7) and sly-negative (DH5) strains indicated that two alternative arrangements are both flanked by genes with highest similarity to haloacid dehalogenase-like hydrolases (5' end) and putative N-acetylmannosamine-6-phosphate epimerases (3' end). However, sly appears to be completely absent from the alternative arrangement, and a gene of unknown function is located in the equivalent position. Finally, PCR analysis of multiple sly-positive and -negative strains indicated that these two alternative genetic arrangements are conserved among many S. suis isolates. PMID:11705935

  2. Trauma-Induced Giant Pyogenic Granuloma in the Upper Lip.

    PubMed

    de Carvalho, Fabrcio Kitazono; Pinheiro, Tiago Novaes; Arid, Juliana; de Queiroz, Alexandra Mussolino; de Rossi, Andiara; Nelson-Filho, Paulo

    2015-01-01

    Pyogenic granuloma (PG) is a reactive local benign vascular lesion, where connective tissue fibrovascular proliferation occurs. The most common etiology of PG is chronic, low-level irritation. PG affects females mainly. The purpose of this paper is to report a giant pyogenic granuloma caused by an acute trauma in the upper lip of an 11-year-old boy. The initial clinical diagnosis suggested PG, which was confirmed after an excisional biopsy and a microscopic exam. Oral lesions of large proportions in children can cause functional, esthetic, and behavioral issues, and should be promptly investigated. PMID:26731254

  3. [Pyogenic granuloma of inferior turbinate: a case report].

    PubMed

    Zhang, Shusheng; Liu, Yanli; Jiang, Zheng

    2015-06-01

    A case of pyogenic granuloma occurred in inferior turbinate was reported and the literatures were reviewed. A 32 years old male patient with left side progressive stuffy nose and repeated epistaxis. Nasal endoscopic examination showed a dark red neoplasm in left nasal cavity and blocked the anterior naris. Nasal cavity enhanced CT showed the neoplasm located in the front of left nasal cavity with marked enhancement. Bilateral sinuses were normal and there was no significant bone destruction. Nasal endoscopic surgery was performed under local anesthesia. Postoperative pathology report showed pyogenic granuloma (granulation tissue type of angioneoplasm). PMID:26514014

  4. The novel species Streptococcus tigurinus and its association with oral infection.

    PubMed

    Zbinden, Andrea; Bostanci, Nagihan; Belibasakis, Georgios N

    2015-01-01

    Streptococcus tigurinus is a novel species of viridans streptococci, shown to cause severe invasive infections such as infective endocarditis, spondylodiscitis and meningitis. S. tigurinus belongs to the Streptococcus mitis group and is most closely related to Streptococcus mitis, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus pseudopneumoniae and Streptococcus infantis. The presence of S. tigurinus in the human oral cavity has been documented, including in patients with periodontal disease. This review addresses the available scientific knowledge on S. tigurinus and its association with closely related streptococci, and discusses its putative involvement in common oral infections. While there is as yet no strong evidence on the involvement of S. tigurinus with oral infections, its presence in the oral cavity and its association with endocarditis warrants special attention for a link between oral and systemic infection. PMID:25483862

  5. The novel species Streptococcus tigurinus and its association with oral infection

    PubMed Central

    Zbinden, Andrea; Bostanci, Nagihan; Belibasakis, Georgios N

    2015-01-01

    Streptococcus tigurinus is a novel species of viridans streptococci, shown to cause severe invasive infections such as infective endocarditis, spondylodiscitis and meningitis. S. tigurinus belongs to the Streptococcus mitis group and is most closely related to Streptococcus mitis, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus pseudopneumoniae and Streptococcus infantis. The presence of S. tigurinus in the human oral cavity has been documented, including in patients with periodontal disease. This review addresses the available scientific knowledge on S. tigurinus and its association with closely related streptococci, and discusses its putative involvement in common oral infections. While there is as yet no strong evidence on the involvement of S. tigurinus with oral infections, its presence in the oral cavity and its association with endocarditis warrants special attention for a link between oral and systemic infection. PMID:25483862

  6. Streptococcus bovis meningitis and hemorrhoids.

    PubMed

    Smith, Adam Hewitt; Sra, Harminder K; Bawa, Sandeep; Stevens, Richard

    2010-07-01

    We report a case of Streptococcus bovis (Streptococcus gallolyticus subsp. pasteurianus) meningitis, a rare cause of central nervous system (CNS) infection in an adult, and comment on the importance of investigation of the lower gastrointestinal tract to identify a portal of entry in cases of systemic Streptococcus bovis infection. PMID:20421434

  7. Streptococcus Adherence and Colonization

    PubMed Central

    Nobbs, Angela H.; Lamont, Richard J.; Jenkinson, Howard F.

    2009-01-01

    Summary: Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed. PMID:19721085

  8. Relatedness of Streptococcus canis from canine streptococcal toxic shock syndrome and necrotizing fasciitis.

    PubMed Central

    DeWinter, L M; Prescott, J F

    1999-01-01

    The emergence of streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) in dogs caused by Streptococcus canis has been reported by our laboratory. Since clonal expansion is thought to be partially responsible for the spread of invasive strains of Streptococcus pyogenes in humans, the relatedness of 15 isolates of S. canis from canine STSS and/or NF was examined using pulsed field gel electrophoresis and biotyping; production of proteases and of a CAMP-like reaction were also examined. Only 2 of the 15 STSS and/or NF isolates were clonally related, suggesting that the emergence of canine STSS/NF is not the result of clonal expansion of one or more highly virulent strains of S. canis. All of the isolates produced proteases and demonstrated a CAMP-like reaction, which appear to be additional characteristics of S. canis. PMID:10369564

  9. Multiple pyogenic granulomas on the face after landmine injury.

    PubMed

    Bakan, Vedat; Aliagaoglu, Cihangir; Yildiz, Abdullah; Emsen, Murat

    2008-01-01

    In this report, we present a 13-year-old male patient with multiple pyogenic granulomas (PG) on the face after landmine injury. To the best of our knowledge, PG after landmine injury has not been reported previously. The case has been reported in view of its rarity and its etiology. PMID:18577058

  10. Internal jugular vein pyogenic capillary hemangioma: a case report.

    PubMed

    Cera, Chiara; Calvagna, Cristiano; Sgorlon, Giada; Zamolo, Francesca; Pancrazio, Francesco; Adovasio, Roberto

    2015-02-01

    Internal jugular vein hemangioma, also called pyogenic granuloma, is a rare tumor. Such a neoformation was accidentally discovered and excised in a middle-aged man. Histologic and immunohistochemical investigations were performed, and this case is compared with the poor amount of similar ones described in the literature. PMID:25462549

  11. [Thousand faces of Streptococcus pneumonia (pneumococcus) infections].

    PubMed

    Szab, Blint Gergely; Lnrt, Katalin Szidnia; Kdr, Bla; Gombos, Andrea; Dezsnyi, Balzs; Szanka, Judit; Bobek, Ilona; Prinz, Gyula

    2015-11-01

    Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35-40% of community acquired adult pneumonias requiring hospitalization, while 25-30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5-7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ?50 years and high risk patients of ?18 years who are susceptible to pneumococcal disease. PMID:26498896

  12. Are Pyogenic Liver Abscesses Still a Surgical Concern? A Western Experience

    PubMed Central

    Alkofer, Barbara; Dufay, Corentin; Parienti, Jean Jacques; Lepennec, Vincent; Dargere, Sylvie; Chiche, Laurence

    2012-01-01

    Backgrounds. Pyogenic liver abscess is a rare disease whose management has shifted toward greater use of percutaneous drainage. Surgery still plays a role in treatment, but its indications are not clear. Method. We conducted a retrospective study of pyogenic abscess cases admitted to our university hospital between 1999 and 2010 and assessed the factors potentially associated with surgical treatment versus medical treatment alone. Results. In total, 103 liver abscess patients were treated at our center. The mortality was 9%. The main symptoms were fever and abdominal pain. All of the patients had CRP > 6?g/dL. Sixty-nine patients had a unique abscess. Seventeen patients were treated with antibiotics alone and 57 with percutaneous drainage and antibiotics. Twenty-seven patients who were treated with percutaneous techniques required surgery, and 29 patients initially received it. Eventually, 43 patients underwent abscess surgery. The factors associated with failed medical treatment were gas-forming abscess (P = 0.006) and septic shock at the initial presentation (P = 0.008). Conclusion. Medical and percutaneous treatment constitute the standard management of liver abscess cases. Surgery remains necessary after failure of the initial treatment but should also be considered as an early intervention for cases presenting with gas-forming abscesses and septic shock and when treatment of the underlying cause is immediately required. PMID:22536008

  13. Pyogenic liver abscess: a 7-year experience in a large community hospital.

    PubMed

    Bissada, A A; Bateman, J

    1991-08-01

    This is a retrospective study of 27 consecutive patients with a diagnosis of pyogenic liver abscess (PLA) seen over a period of 7 years. There were 10 males and 17 females whose ages ranged from 5 to 86 years (mean 56). Fever, abdominal pain and vomiting were the commonest symptoms, and abdominal tenderness was the commonest physical finding. An elevated alkaline phosphatase was seen in 78% of all patients and was the commonest biochemical abnormality. Biliary disease accounted for a third of all cases, and in 22% of the patients the abscesses were considered to be idiopathic. Ultrasonography and/or CT scanning was employed in the diagnosis and follow-up of all patients. Percutaneous needle aspiration (PNA) and percutaneous drainage (PCD) under ultrasound or CT guidance was employed as the primary therapy in 24 patients. The procedure failed in 5 patients (18.5%), there was 1 complication (3.7%) and no deaths were seen as a result of these procedures. Three patients (11%) ultimately died of their abscesses. This study emphasizes the important role of percutaneous drainage as a complementary form of therapy to surgical drainage in the management of pyogenic liver abscesses. PMID:1937379

  14. Streptococcus pneumoniae septic arthritis in adults.

    PubMed

    James, P A; Thomas, M G

    2000-01-01

    Septic arthritis is a rarely reported manifestation of disease due to Streptococcus pneumoniae. We have reviewed our recent experience of this disease in 14 adult patients. Common features in patients with S. pneumoniae septic arthritis included advanced age (median=63 y), pre-existing joint disease (6/14), large joint disease (14/14), polyarthritis (6/14), and associated meningitis, pneumonia or both (6/14). Two patients with septic arthritis and meningitis, and another with Down's syndrome and sleep apnoea, died during treatment. In the remaining 11 patients, treatment for at least 19 d, predominantly with intravenous benzyl penicillin, plus joint lavage, resulted in cure. PMID:11055652

  15. Streptococcus iniae vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus iniae is among the most important emergent pathogens that affects many fish species worldwide, especially in warm-water regions. In marine and freshwater systems, this Gram-positive bacterium causes significant economic losses, estimated at hundreds of millions of dollars annually. Inf...

  16. Robust Antigen Specific Th17 T Cell Response to Group A Streptococcus Is Dependent on IL-6 and Intranasal Route of Infection

    PubMed Central

    Moon, James J.; Pepper, Marion; Jenkins, Marc K.; Cleary, Patrick P.

    2011-01-01

    Group A streptococcus (GAS, Streptococcus pyogenes) is the cause of a variety of clinical conditions, ranging from pharyngitis to autoimmune disease. Peptide-major histocompatibility complex class II (pMHCII) tetramers have recently emerged as a highly sensitive means to quantify pMHCII-specific CD4+ helper T cells and evaluate their contribution to both protective immunity and autoimmune complications induced by specific bacterial pathogens. In lieu of identifying an immunodominant peptide expressed by GAS, a surrogate peptide (2W) was fused to the highly expressed M1 protein on the surface of GAS to allow in-depth analysis of the CD4+ helper T cell response in C57BL/6 mice that express the I-Ab MHCII molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I-Ab-specific CD4+ T cells were identified in the nasal-associated lymphoid tissue (NALT) that produced IL-17A or IL-17A and IFN-? if infection was recurrent. The dominant Th17 response was also dependent on the intranasal route of inoculation; intravenous or subcutaneous inoculations produced primarily IFN-?+ 2W:I-Ab+ CD4+ T cells. The acquisition of IL-17A production by 2W:I-Ab-specific T cells and the capacity of mice to survive infection depended on the innate cytokine IL-6. IL-6-deficient mice that survived infection became long-term carriers despite the presence of abundant IFN-?-producing 2W:I-Ab-specific CD4+ T cells. Our results suggest that an imbalance between IL-17- and IFN-?-producing CD4+ T cells could contribute to GAS carriage in humans. PMID:21966268

  17. The changing faces of Streptococcus antigen I/II polypeptide family adhesins

    PubMed Central

    Brady, L. Jeannine; Maddocks, Sarah E.; Larson, Matthew R.; Forsgren, Nina; Persson, Karina; Deivanayagam, Champion C.; Jenkinson, Howard F.

    2010-01-01

    Summary Streptococcus mutans antigen I/II (AgI/II) protein was one of the first cell-wall anchored adhesins identified in Gram-positive bacteria. It mediates attachment of Streptococcus mutans to tooth surfaces and has been a focus for immunization studies against dental caries. The AgI/II family polypeptides recognize salivary glycoproteins, and are also involved in biofilm formation, platelet aggregation, tissue invasion, and immune modulation. The genes encoding AgI/II family polypeptides are found amongst Streptococcus species indigenous to the human mouth, as well as in S. pyogenes, S. agalactiae, and S. suis. Evidence of functionalities for different regions of the AgI/II proteins has emerged. A sequence motif within the C-terminal portion of Streptococcus gordonii SspB (AgI/II) is bound by Porphyromonas gingivalis, thus promoting oral colonization by this anaerobic pathogen. The significance of other epitopes is now clearer following resolution of regional crystal structures. A new picture emerges of the central V (variable) region, predicted to contain a carbohydrate-binding trench, being projected from the cell surface by a stalk formed by an unusual association between an amino-terminal ?-helix and a carboxy-terminal polyproline helix. This presentation mode might be important in determining functional conformations of other Gram-positive surface proteins that have adhesin domains flanked by ?-helical and proline-rich regions. PMID:20497507

  18. Two Novel Superantigens Found in Both Group A and Group C Streptococcus

    PubMed Central

    Proft, Thomas; Webb, Phillip D.; Handley, Vanessa; Fraser, John D.

    2003-01-01

    Two novel streptococcal superantigen genes (speLSe and speMSe) were identified from the Streptococcus equi genome database at the Sanger Center. Genotyping of 8 S. equi isolates and 40 Streptococcus pyogenes isolates resulted in the detection of the orthologous genes speL and speM in a restricted number of S. pyogenes isolates (15 and 5%, respectively). Surprisingly, the novel superantigen genes could not be found in any of the analyzed S. equi isolates. The results suggest that both genes are located on a mobile element that enables gene transfer between individual isolates and between streptococci from different Lancefield groups. S. equi pyrogenic exotoxin L (SPE-LSe)/streptococcal pyrogenic exotoxin L (SPE-L) and SPE-MSe/SPE-M are most closely related to SMEZ, SPE-C, SPE-G, and SPE-J, but build a separate branch within this group. Recombinant SPE-L (rSPE-L) and rSPE-M were highly mitogenic for human peripheral blood lymphocytes, with half-maximum responses at 1 and 10 pg/ml, respectively. The results from competitive binding experiments suggest that both proteins bind major histocompatibility complex class II at the ?-chain, but not at the ?-chain. The most common targets for both toxins were human V?1.1 expressing T cells. Seroconversion against SPE-L and SPE-M was observed in healthy blood donors, suggesting that the toxins are expressed in vivo. Interestingly, the speL gene is highly associated with S. pyogenes M89, a serotype that is linked to acute rheumatic fever in New Zealand. PMID:12595453

  19. Highly efficient heritable plant genome engineering using Cas9 orthologues from Streptococcus thermophilus and Staphylococcus aureus.

    PubMed

    Steinert, Jeannette; Schiml, Simon; Fauser, Friedrich; Puchta, Holger

    2015-12-01

    The application of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system of Streptococcus pyogenes (SpCas9) is currently revolutionizing genome engineering in plants. However, synthetic plant biology will require more complex manipulations of genomes and transcriptomes. The simultaneous addressing of different specific genomic sites with independent enzyme activities within the same cell is a key to this issue. Such approaches can be achieved by the adaptation of additional bacterial orthologues of the CRISPR/Cas system for use in plant cells. Here, we show that codon-optimised Cas9 orthologues from Streptococcus thermophilus (St1Cas9) and Staphylococcus aureus (SaCas9) can both be used to induce error-prone non-homologous end-joining-mediated targeted mutagenesis in the model plant Arabidopsis thaliana at frequencies at least comparable to those that have previously been reported for the S.pyogenes CRISPR/Cas system. Stable inheritance of the induced targeted mutations of the ADH1 gene was demonstrated for both St1Cas9- and SaCas9-based systems at high frequencies. We were also able to demonstrate that the SaCas9 and SpCas9 proteins enhance homologous recombination via the induction of double-strand breaks only in the presence of their species-specific single guide (sg) RNAs. These proteins are not prone to inter-species interference with heterologous sgRNA expression constructs. Thus, the CRISPR/Cas systems of S.pyogenes and S.aureus should be appropriate for simultaneously addressing different sequence motifs with different enzyme activities in the same plant cell. PMID:26576927

  20. Efficacy of the Canine Influenza Virus H3N8 Vaccine To Decrease Severity of Clinical Disease after Cochallenge with Canine Influenza Virus and Streptococcus equi subsp. zooepidemicus ▿

    PubMed Central

    Larson, Laurie J.; Henningson, Jamie; Sharp, Patricia; Thiel, Bliss; Deshpande, Muralidhar S.; Davis, Tamara; Jayappa, Huchappa; Wasmoen, Terri; Lakshmanan, Nallakannu; Schultz, Ronald D.

    2011-01-01

    Since first emerging in the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. The severity of disease is variable, and coinfection by other respiratory pathogens is an important factor in the degree of morbidity and mortality. The first influenza vaccine for dogs, an inactivated vaccine containing CIV subtype H3N8, was conditionally approved by the U.S. Department of Agriculture (USDA) for licensure in May 2009 and fully licensed in June 2010. This study evaluates the efficacy of this vaccine to reduce the severity of illness in dogs cochallenged with virulent CIV and Streptococcus equi subsp. zooepidemicus. PMID:21346059

  1. Hepatogastric fistula: a rare complication of pyogenic liver abscess.

    PubMed

    Gandham, Venkata Srinivas; Pottakkat, Biju; Panicker, Lakshmi C; Hari, Ranjit Vijaya

    2014-01-01

    Hepatogastric fistula is very rare. We report a case of hepatogastric fistula as a complication of pyogenic liver abscess. A 40-year-old man presented with upper abdominal pain and high-grade fever of 2?weeks. Evaluation revealed multiple liver abscesses. On an empirical diagnosis of pyogenic liver abscess, he was treated with antibiotics. During hospital stay he developed intermittent large quantity bilious vomiting. Gastroduodenoscopy and contrast-enhanced CT of the abdomen showed rupture of left lobe liver abscess into the stomach. As expectant management failed to resolve the abscess, endoscopic retrograde papillotomy and stenting of common bile duct was performed. After endoscopic stenting, symptoms subsided. Imaging repeated after 2 weeks of endoscopic stenting showed resolving abscess. He was discharged and is doing well on regular follow-ups. We conclude that hepatogastric fistula can be managed by endoscopic stenting as bile flow through the stent hastens resolution and healing of the fistula. PMID:25035445

  2. Controlled laboratory challenge demonstrates substantial additive genetic variation in resistance to Streptococcus iniae in Nile tilapia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus iniae is an etiologic agent of streptococcal disease in tilapia and is one of several Streptococcus spp. that negatively impact worldwide tilapia production. Methods for the prevention and control of S. iniae include vaccines, management strategies, and antibiotics. An alternative and ...

  3. Intravascular laser therapy in different forms of lung diseases

    NASA Astrophysics Data System (ADS)

    Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.

    1993-06-01

    The potentions of laser intravascular therapy in elimination of pyogenic and inflammatory intoxication in cases of acute pneumonia, pyo-destructive diseases (including posttraumatic diseases) of the lungs are studied clinically.

  4. Cloning and characterization of a novel macrolide efflux gene, mreA, from Streptococcus agalactiae.

    PubMed Central

    Clancy, J; Dib-Hajj, F; Petitpas, J W; Yuan, W

    1997-01-01

    A strain of Streptococcus agalactiae displayed resistance to 14-, 15-, and 16-membered macrolides. In PCR assays, total genomic DNA from this strain contained neither erm nor mef genes. EcoRI-digested genomic DNA from this strain was cloned into lambda Zap II to construct a library of S. agalactiae genomic DNA. A clone, pAES63, expressing resistance to erythromycin, azithromycin, and spiramycin in Escherichia coli was recovered. Deletion derivatives of pAES63 which defined a functional region on this clone that encoded resistance to 14- and 15-membered, but not 16-membered, macrolides were produced. Studies that determined the levels of incorporation of radiolabelled erythromycin into E. coli were consistent with the presence of a macrolide efflux determinant. This putative efflux determinant was distinct from the recently described Mef pump in Streptococcus pyogenes and Streptococcus pneumoniae and from the multicomponent MsrA pump in Staphylococcus aureus and coagulase-negative staphylococci. Its gene has been designated mreA (for macrolide resistance efflux). PMID:9420045

  5. A Genome-Wide Profiling Strategy as an Aid for Searching Unique Identification Biomarkers for Streptococcus.

    PubMed

    Kalia, Vipin Chandra; Kumar, Ravi; Kumar, Prasun; Koul, Shikha

    2016-03-01

    The use of rrs (16S rRNA) gene is widely regarded as the "gold standard" for identifying bacteria and determining their phylogenetic relationships. Nevertheless, multiple copies of this gene in a genome is likely to give an overestimation of the bacterial diversity. In each of the 50 Streptococcus genomes (16 species, 50 strains), 4-7 copies of rrs are present. The nucleotide sequences of these rrs genes show high similarity within and among genomes, which did not allow unambiguous identification. A genome-wide search revealed the presence of 27 gene sequences common to all the Streptococcus species. Digestion of these 27 gene sequences with 10 type II restriction endonucleases (REs) showed that unique RE digestion in purH gene is sufficient for clear cut identification of 30 genomes belonging to 16 species. Additional gene-RE combinations allowed identification of another 15 strains belonging to S. pneumoniae, S. pyogenes, and S. suis. For the rest 5 strains, a combination of 2 genes was required for identifying them. The proposed strategy is likely to prove helpful in proper detection of pathogens like Streptococcus. PMID:26843696

  6. Considerations for a phase-III trial to evaluate a group B Streptococcus polysaccharide-protein conjugate vaccine in pregnant women for the prevention of early- and late-onset invasive disease in young-infants.

    PubMed

    Madhi, Shabir A; Dangor, Ziyaad; Heath, Paul T; Schrag, Stephanie; Izu, Alaine; Sobanjo-Ter Meulen, Ajoke; Dull, Peter M

    2013-08-28

    In 2010, an estimated 393,000 infection-related neonatal deaths occurred worldwide with Group B streptococcus (GBS) being a leading cause. Prevention of early-onset disease (0-6 days; EOD) is currently focused on intra-partum antibiotic prophylaxis to mothers identified as being at risk; such strategies reduce EOD by 75-80% but are resource-intensive and logistically-difficult to implement in developing countries. Vaccination of pregnant women is an alternate strategy for preventing both EOD and late-onset disease (7-89 days; LOD). A trivalent GBS polysaccharide-protein conjugate vaccine (GBS-CV) composed of capsular epitopes from serotypes Ia, Ib and III is undergoing phase-II evaluation among pregnant women in Europe, North America and Africa. These serotypes cause 70-80% of all invasive GBS disease in early-infancy. Maternal anti-GBS antibodies are associated with protection from EOD, however, since a correlate of efficacy has not been defined, a phase III efficacy trial may be required for licensure. Criteria for selecting appropriate sites include sufficiently high GBS incidence in large birth cohorts, as well as adequate clinical and microbiological diagnostic skills and capacities. Alternate pathways to licensure should be explored, e.g. identification of serological correlates of protection with subsequent phase IV studies establishing vaccine-effectiveness against invasive GBS disease. Conducting a randomized, placebo-controlled efficacy trial, however, has the additional advantage of also being able to evaluate the role of GBS contributing to neonatal culture-negative sepsis, stillbirths, prematurity and low-birth weight. PMID:23973347

  7. Gas-Forming Pyogenic Liver Abscess with Septic Shock.

    PubMed

    Khan, Muhammad S; Ishaq, Muhammad K; Jones, Kellie R

    2015-01-01

    The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its ?-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens. PMID:26090240

  8. Gas-Forming Pyogenic Liver Abscess with Septic Shock

    PubMed Central

    Ishaq, Muhammad K.; Jones, Kellie R.

    2015-01-01

    The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its ?-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens. PMID:26090240

  9. GENOMIC DIVERSITY OF STREPTOCOCCUS AGALACTIAE FROM FISH, BOVINE AND HUMAN HOSTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Group B Streptococcus agalactiae (GBS) is a cause of infectious disease in multiple poikilothermic and homothermic animal species. Epidemiological and zoonotic considerations necessitate an undertaking of a comparison of S. agalactiae isolates from different phylogenetic hosts and geographical regi...

  10. AN OVERVIEW STREPTOCOCCUS IN WARM-WATER FISH

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite being known mainly as mammalian disease agents, Streptococcus iniae and S. agalactiae have become recognized as emerging pathogens of wild and cultured fish. The worldwide economic impact of S. iniae and S. agalactiae to the aquaculture industry is estimated in hundreds of millions annually...

  11. Streptococcus mutans, caries and simulation models.

    PubMed

    Forssten, Sofia D; Björklund, Marika; Ouwehand, Arthur C

    2010-03-01

    Dental caries and dental plaque are among the most common diseases worldwide, and are caused by a mixture of microorganisms and food debris. Specific types of acid-producing bacteria, especially Streptococcus mutans, colonize the dental surface and cause damage to the hard tooth structure in the presence of fermentable carbohydrates e.g., sucrose and fructose. This paper reviews the link between S. mutans and caries, as well as different simulation models that are available for studying caries. These models offer a valuable approach to study cariogenicity of different substrates as well as colonization of S. mutans. PMID:22254021

  12. Virulence determinants and biofilm production among Trueperella pyogenes recovered from abscesses of captive forest musk deer.

    PubMed

    Zhao, Kelei; Tian, Yongqiang; Yue, Bisong; Wang, Hongning; Zhang, Xiuyue

    2013-03-01

    Trueperella pyogenes (formerly Arcanobacterium) is commonly isolated from domesticated or wild ruminants as an opportunistic pathogen. To investigate the role of virulence determinants (VDs) and biofilm production in T. pyogenes isolates, a total of 36 T. pyogenes were collected from abscesses of forest musk deer in Miyaluo Farm (Sichuan Province, China). The prevalence of VDs and associations with clonal types, antibiotic resistance and biofilm production were analyzed by PCR and bioassay. Finally, T. pyogenes isolates were separated into three clonal types based on the DNA fingerprinting of BOX-PCR. Isolates with less VDs obtained from sick forest musk deer were mainly belonged to Type 1, and the isolates with robust VD repertoire obtained from dead forest musk deer were included in Type 3. Accordingly, resistant isolates exhibited significant lower virulence than susceptible ones. Majority of T. pyogenes isolates of this study were capable of producing a biofilm. However, no VDs presence and antibiotic resistance were statistically associated with biofilm production. In conclusion, the current study demonstrated that T. pyogenes was probably the primary pathogen of abscesses in the forest musk deer. Moreover, as an animal origin pathogen, the increasing resistance of T. pyogenes isolates could also associate with a decreased virulence. PMID:23354327

  13. Pyogenic granuloma in relation to dental implants: Clinical and histopathological findings

    PubMed Central

    Pinas, Laura

    2015-01-01

    Background The occurrence of pyogenic granuloma in association to dental implants is rare and only five cases have been reported in the literature. Material and Methods Patients charts were analyzed to select patients who had been diagnosed for pyogenic granuloma and its association with dental implants had been evaluated. The clinical status of the dental implants and the prosthesis had also been assessed. Results Clinical and histopathological diagnosis of pyogenic granuloma had been reached for soft mass growth in association with dental implants in 10 patients. Histological analysis of all samples was performed to obtain a firm diagnosis of finding against pyogenic granuloma lesions. Accumulation of dental plaque due to poor oral hygiene and improper design of the prosthesis had been related to the occurrence of pyogenic granuoloma. This lesion showed no predilection to specific surface type and had no significant association with marginal bone loss. Conclusions Pyogenic granuloma should be included in the differential diagnosis of soft mass growth around dental implants. Key words:Reactive lesion, soft mass, pyogenic granuloma, dental implant, titanium. PMID:26535087

  14. Plants used in Guatemala for the treatment of respiratory diseases. 1. Screening of 68 plants against gram-positive bacteria.

    PubMed

    Caceres, A; Alvarez, A V; Ovando, A E; Samayoa, B E

    1991-02-01

    Respiratory ailments are important causes of morbidity and mortality in developing countries. Ethnobotanical surveys and literature reviews conducted in Guatemala during 1986-88 showed that 234 plants from 75 families, most of them of American origin, have been used for the treatment of respiratory ailments. Three Gram-positive bacteria causing respiratory infections (Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes) were used to screen 68 of the most commonly used plants for activity. Twenty-eight of these (41.2%) inhibited the growth of one or more of the bacteria tested. Staphylococcus aureus was inhibited by 18 of the plant extracts, while 7 extracts were effective against Streptococcus pyogenes. Plants of American origin which exhibited antibacterial activity were: Gnaphalium viscosum, Lippia alba, Lippia dulcis, Physalis philadelphica, Satureja brownei, Solanum nigrescens and Tagetes lucida. These preliminary in vitro results provide scientific basis for the use of these plants against bacterial respiratory infections. PMID:2023428

  15. Small plasmids in Streptococcus dysgalactiae subsp. equisimilis isolated from human infections in southern India and sequence analysis of two novel plasmids.

    PubMed

    Bergmann, Ren; Nitsche-Schmitz, D Patric

    2015-05-01

    Small plasmids are frequently found in S. pyogenes isolates from human infections in India. Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a streptococcal subspecies that is genetically similar to S. pyogenes and has a similar ecology. Therefore, we determined the distribution of small plasmids in a collection of 254 SDSE isolates, comprising 44 different emm-types and emm non-typable strains, from southern India, utilizing an established PCR based method. Briefly, 1.2% (n=3) of the isolates were positive for repA (encoding the replication initiation protein A) and 1.6% (n=4) were repB positive (encoding the replication initiation protein B). One isolate (G315) showed a co-detection of repB and dysA (encoding the bacteriocin dysgalacticin) which is characteristic for previously described pDN281/pW2580-like plasmids, observed in SDSE and S. pyogenes. The remaining plasmid bearing isolates showed no characteristic co-detection of known plasmid-associated genes. Thus, plasmids pG271 and pG279, representatives for repB and repA harboring plasmids, respectively, were analyzed. The plasmids pG271 and pG279 could be assigned to the pMV158 and the pC194/pUB110 family of rolling-circle plasmids, respectively. Like the characterized small native plasmids of S. pyogenes from India, the SDSE plasmids discovered and described in this study did not carry any of the known antibiotic resistance genes. SDSE bore less of the investigated small native plasmids that were distinct from the small native plasmids of S. pyogenes of the same geographic region. This indicates a low rate of lateral transfer of these genetic elements between these two related streptococcal species. PMID:25769407

  16. Surface-associated properties of Streptococcus milleri group strains and their potential relation to pathogenesis.

    PubMed

    Willcox, M D; Knox, K W

    1990-04-01

    Thirty strains from the Streptococcus milleri (anginosus) group (SMG) obtained from various sources were tested for a range of characters that could be associated with pathogenicity and the results were compared with those for type strains of S. sanguis, S. mutans and S. pyogenes. The SMG strains were heterogeneous in all tests. Most (18) belonged to one of the Lancefield groups with group F predominating. Adherence of strains isolated from abscesses to buccal epithelial cells was greater than that of other strains (p = 0.033). Compared with strains of S. sanguis, SMG strains were generally not aggregated by human saliva. They differed from the type strain of S. pyogenes in their relative ability to bind fibrinogen and fibronectin; they were less effective in binding fibrinogen (0.33-4.28% cf. 22% for S. pyogenes) and generally more effective in binding fibronectin (0.49-12.37% cf. 0.95%). Strains isolated from infections were statistically better at binding fibronectin than other strains (p less than 0.001). The ability of strains to adhere to saliva-coated hydroxyapatite (SHA) varied 10-fold, from 0.16-16.35%. The amount of fibronectin bound by SMG strains correlated with their ability to adhere to SHA (p less than 0.001). The hydrophobicity of the strains, as measured in the hexadecane partition assay, ranged from 0.0% to 99.0%. Some strains carried both positive and negative cell-surface charges and some strains with a highly hydrophobic cell surface also possessed a relatively high cell-surface charge. A minority of strains possessed a net positive cell-surface charge. Neither hydrophobicity nor cell-surface charge was related to the capacity of strains to adhere to SHA. Strains of SMG co-aggregated weakly with strains of Veillonella parvula, V. dispar, Actinomyces viscosus and A. naeslundii. PMID:2325115

  17. Red, exophytic nodule of the plantar foot an unusual presentation of a pyogenic granuloma.

    PubMed

    Kober, Mary-Margaret; Alapati, Usha; Khachemoune, Amor

    2015-03-01

    Pyogenic granulomas are benign vascular tumors characterized histologically by a lobular proliferation of capillaries. We report an unusual presentation of a pyogenic granuloma in an elderly patient with a bleeding red nodule on the plantar surface of the foot. Nodular exophytic plantar foot lesions often present a diagnostic challenge, as the differential diagnosis includes benign and malignant entities ranging from eccrine poroma and pyogenic granuloma to Kaposi's sarcoma and amelanotic melanoma. This case highlights the need for an adequate biopsy technique to confirm the diagnosis and guide management. PMID:25815662

  18. Molecular Characterization of Invasive Streptococcus dysgalactiae subsp. equisimilis, Japan.

    PubMed

    Wajima, Takeaki; Morozumi, Miyuki; Hanada, Shigeo; Sunaoshi, Katsuhiko; Chiba, Naoko; Iwata, Satoshi; Ubukata, Kimiko

    2016-02-01

    We collected ?-hemolytic streptococci (1,611 isolates) from patients with invasive streptococcal infections in Japan during April 2010-March 2013. Streptococcus dysgalactiae subsp. equisimilis (SDSE) was most common (n = 693); 99% of patients with SDSE infections were elderly (mean age 75 years, SD 15 years). We aimed to clarify molecular and epidemiologic characteristics of SDSE isolates and features of patient infections. Bacteremia with no identified focus of origin and cellulitis were the most prevalent manifestations; otherwise, clinical manifestations resembled those of S. pyogenes infections. Clinical manifestations also differed by patient's age. SDSE isolates were classified into 34 emm types; stG6792 was most prevalent (27.1%), followed by stG485 and stG245. Mortality rates did not differ according to emm types. Multilocus sequence typing identified 46 sequence types and 12 novel types. Types possessing macrolide- and quinolone-resistance genes were 18.4% and 2.6%, respectively; none showed ?-lactam resistance. Among aging populations, invasive SDSE infections are an increasing risk. PMID:26760778

  19. Molecular Characterization of Invasive Streptococcus dysgalactiae subsp. equisimilis, Japan

    PubMed Central

    Wajima, Takeaki; Morozumi, Miyuki; Hanada, Shigeo; Sunaoshi, Katsuhiko; Chiba, Naoko; Iwata, Satoshi

    2016-01-01

    We collected β-hemolytic streptococci (1,611 isolates) from patients with invasive streptococcal infections in Japan during April 2010–March 2013. Streptococcus dysgalactiae subsp. equisimilis (SDSE) was most common (n = 693); 99% of patients with SDSE infections were elderly (mean age 75 years, SD ±15 years). We aimed to clarify molecular and epidemiologic characteristics of SDSE isolates and features of patient infections. Bacteremia with no identified focus of origin and cellulitis were the most prevalent manifestations; otherwise, clinical manifestations resembled those of S. pyogenes infections. Clinical manifestations also differed by patient’s age. SDSE isolates were classified into 34 emm types; stG6792 was most prevalent (27.1%), followed by stG485 and stG245. Mortality rates did not differ according to emm types. Multilocus sequence typing identified 46 sequence types and 12 novel types. Types possessing macrolide- and quinolone-resistance genes were 18.4% and 2.6%, respectively; none showed β-lactam resistance. Among aging populations, invasive SDSE infections are an increasing risk. PMID:26760778

  20. Autoimmune diseases: Solution of the environmental, immunological and genetic components with principles for immunotherapy and transplantation.

    PubMed

    Adams, Duncan D; Knight, John G; Ebringer, Alan

    2010-06-01

    Autoimmune diseases have environmental and genetic components. These are the microbial trigger, the immunity system component and the genetic component. Here we describe these components and how they interact. Known microbial triggers are Streptococcus pyogenes for rheumatic carditis, Proteus mirabilis for rheumatoid arthritis and Klebsiella pneumoniae for ankylosing spondylitis. The immunity system component has been clarified by realisation that no autoimmune disease is caused by loss of suppressor T cells. This leaves Burnet's forbidden clones, clearly seen in Graves' disease, as the immunological defect. With wide scope for clonal diversification by somatic gene mutations, to prevent frequent autoimmunity the immunity system is policed by the histocompatibility system. This dictates the immune response repertoire by deleting complementary clones (H Gene Theory). We show molecular evidence of how specific histocompatibility antigens can predispose to an autoimmune disease by influencing choice of the microbial antigen to which the immunity system reacts. Because of the unlucky random element in the somatic mutations involved in their development, forbidden clones are unlikely to reappear in new immune repertoires developing after immune ablation and autologous bone marrow cell reconstitution, as observed clinically. Isolation of autoantigens and their attachment to cytotoxic moieties could provide specific immunotherapy for autoimmune diseases. Kaplans's discovery that xenografts can be accepted without rejection after immune ablation followed by autologous and xenogeneic bone marrow inoculation, could enable widespread use of pig grafts for humans. PMID:20083235

  1. Adherence of Veillonella Species Mediated by Extracellular Glucosyltransferase from Streptococcus salivarius

    PubMed Central

    McCabe, R. M.; Donkersloot, J. A.

    1977-01-01

    The effect of extracellular products from Streptococcus salivarius on sucrose-dependent adherence to smooth surfaces by other oral bacteria was studied in vitro. Strains of Streptococcus mitis, Streptococcus pyogenes, and Veillonella parvula without innate ability to adhere to a steel wire were able to do so when incubated with sucrose and cell-free culture fluid from S. salivarius strains 9759, 25975, CNII, and MEPI. These culture fluids synthesized more adherent material and water-insoluble glucan than those from Streptococcus mutans C67-1 and seven other S. salivarius strains. Among the S. salivarius strains, glucosyltransferase (GT; dextransucrase, EC 2.4.1.5) activity varied more than 100-fold. Cells of Veillonella and S. mitis S3 that had been incubated in culture fluids from S. salivarius 25975 and 9759, respectively, and then washed adhered upon subsequent incubation with sucrose. This was due to adsorbed GT because (i) the adherence was sensitive to dextranase; (ii) it was observed only with the high-GT culture fluids; (iii) it was dependent on sucrose; and (iv) the washed Veillonella cells synthesized glucan, but not fructan, from sucrose. These results suggest that sucrose-dependent adherence of bacteria without such innate ability can be mediated by (i) entrapment in insoluble glucan synthesized by S. salivarius culture fluids, and (ii) prior adsorption of GT from S. salivarius culture fluids. The possibility that GT formed by high-yield strains of S. salivarius is distributed through the mouth by the action of salivary flow and contributes to sucrose-dependent adherence and plaque formation is considered. Images PMID:591064

  2. Laser: A Powerful Tool for Treatment of Pyogenic Granuloma

    PubMed Central

    Rai, Shalu; Kaur, Mandeep; Bhatnagar, Puneet

    2011-01-01

    Lasers have opened a new door for the treatment of various disorders. Treatment of soft tissue intraoral mucosal growth by laser has profound effect on the patient acceptability taking the functional and aesthetic factor into consideration. The patient is able to get the outdoor treatment without the phobia of local anaesthetic and is out of the clinic in few minutes in contrast to the traditional method of surgical excision. Very few cases have been reported in literature regarding treatment of mucosal growth by soft tissue lasers. We present a case of recurrent pyogenic granuloma in a patient treated with an alternative approach, that is, diode laser, without the use of anaesthesia, sutures, anti-inflammatory drugs, or analgesics. The diagnosis of this lesion is equally important for correct treatment planning. PMID:21976910

  3. Alternative Therapeutic Approach in the Treatment of Oral Pyogenic Granuloma.

    PubMed

    Bugshan, Amr; Patel, Harsh; Garber, Karen; Meiller, Timothy F

    2015-01-01

    Pyogenic granulomas (PGs) in the oral cavity present as an inflammatory hyperplasia usually caused by trauma, hormonal imbalance, chronic irritation, or as the response to a wide variety of drugs. PGs with atypical presentation and behavior may clinically mimic malignant tumors. Thus, histological examination is required to rule out cancer development. Lesions in the oral cavity have been described to be either an isolated entity or present in multiple forms and with multiple recurrences. Conservative surgical excision is the standard choice of treatment in almost every scenario. However, the severity of the lesions and the affected sites often challenge surgical treatment. In this report, we describe the clinical scenario of a recurrent PG, where surgical excision of the lesion was questioned. As an alternative, we describe a noninvasive approach with lesional steroid injections. PMID:26668570

  4. Alternative Therapeutic Approach in the Treatment of Oral Pyogenic Granuloma

    PubMed Central

    Bugshan, Amr; Patel, Harsh; Garber, Karen; Meiller, Timothy F.

    2015-01-01

    Pyogenic granulomas (PGs) in the oral cavity present as an inflammatory hyperplasia usually caused by trauma, hormonal imbalance, chronic irritation, or as the response to a wide variety of drugs. PGs with atypical presentation and behavior may clinically mimic malignant tumors. Thus, histological examination is required to rule out cancer development. Lesions in the oral cavity have been described to be either an isolated entity or present in multiple forms and with multiple recurrences. Conservative surgical excision is the standard choice of treatment in almost every scenario. However, the severity of the lesions and the affected sites often challenge surgical treatment. In this report, we describe the clinical scenario of a recurrent PG, where surgical excision of the lesion was questioned. As an alternative, we describe a noninvasive approach with lesional steroid injections. PMID:26668570

  5. Complete Genome Sequence of Streptococcus agalactiae Serotype III, Multilocus Sequence Type 283 Strain SG-M1

    PubMed Central

    Mehershahi, Kurosh S.; Hsu, Li Yang; Koh, Tse Hsien

    2015-01-01

    Streptococcus agalactiae (group B Streptococcus) is a common commensal strain in the human gastrointestinal tract that can also cause invasive disease in humans and other animals. We report here the complete genome sequence of S. agalactiae SG-M1, a serotype III, multilocus sequence type 283 strain, isolated from a Singaporean patient suffering from meningitis. PMID:26494662

  6. Development of pyogenic granuloma and hemangioma after placement of dental implants: A review of literature

    PubMed Central

    Al-Shamiri, Hashem Motahir; Alaizari, Nader Ahmed; Al-Maweri, Sadeq Ali; Tarakji, Bassel

    2015-01-01

    Aim: The aim of this study is to highlight the development of pyogenic granuloma and hemangioma after the placement of dental implants. Materials and Methods: A literature search was performed using MEDLINE, accessed via the National Library of Medicine PubMed Interface, for articles published between 2000 and 2014 in English, relating to the occurrence of pyogenic granuloma or hemangioma in relation to dental implants. Results: Our search identified only four case reports of pyogenic granuloma and hemangioma related to dental implants as reported in the English literature. Conclusion: Placement of dental implants can cause development of pyogenic granuloma and hemangioma, indicating that placement of dental implants requires well-trained specialists with perfect skills in dental implantology. Furthermore, the critical selection of the appropriate case is of paramount importance to avoid the occurrence of such complications. PMID:25992330

  7. Clinical Characteristics and Risk Factors of Pyogenic Spondylitis Caused by Gram-Negative Bacteria

    PubMed Central

    Kang, Seung-Ji; Jang, Hee-Chang; Jung, Sook-In; Choe, Pyoeng Gyun; Park, Wan Beom; Kim, Chung-Jong; Song, Kyoung-Ho; Kim, Eu Suk; Kim, Hong Bin; Oh, Myoung-don

    2015-01-01

    Background There are limited data describing the clinical characteristics of pyogenic spondylitis caused by Gram-negative bacteria (GNB). The aim of this study was to investigate the predisposing factors and clinical characteristics of pyogenic spondylitis caused by GNB compared to Gram-positive cocci (GPC). Methods We performed a retrospective review of medical records from patients with culture-confirmed pyogenic spondylitis at four tertiary teaching hospitals over an 8-year period. Results A total of 344 patients with culture-confirmed pyogenic spondylitis were evaluated. There were 62 patients (18.0%) with pyogenic spondylitis caused by GNB and the most common organism was Escherichia coli (n = 35, 10.2%), followed by Pseudomonas aeruginosa (n = 10, 2.9%). Pyogenic spondylitis caused by GNB was more frequently associated with the female gender (64.5 vs. 35.5%, P <0.01), preexisting or synchronous genitourinary tract infection (32.3 vs. 2.1%, P< 0.01), and intra-abdominal infection (12.9 vs. 0.4%, P< 0.01) compared to patients with GPC. Although pyogenic spondylitis caused by GNB presented with severe sepsis more frequently (24.2 vs. 11.3%, P = 0.01), the mortality rate (6.0 vs. 5.2%) and the proportion of patients with residual disability (6.0 vs. 9.0%), defined as grade 3 or 4 (P = 0.78) 3 months after completion of treatment, were not significantly different compared to GPC patients. Conclusion GNB should be considered as the etiologic organism when infectious spondylitis develops in a patient with preexisting or synchronous genitourinary tract and intra-abdominal infection. In addition, the mortality rate and clinical outcomes are not significantly different between pyogenic spondylitis caused by GNB and GPC. PMID:25978839

  8. Pyogenic Granuloma of the Sigmoid Colon causing Intussusception in an Infant.

    PubMed

    Garofalo, Salvatore; Mostert, Michael; Morra, Isabella; Cortese, Maria Grazia; Guan, Riccardo; Mussa, Alessandro; Canesi, Mario; Carbonaro, Giulia; Cerrina, Alessia; Ferrero, Luisa; Cussa, Davide; Schleef, Jurgen

    2015-01-01

    Pyogenic granuloma is a benign vascular tumor that may affect the gastrointestinal tract. This report describes a rare case of sigmoid-colon pyogenic granuloma in a 4-month-old boy causing intussusception. Resection and anastomosis were curative. The mother had history of high dose of progesterone exposure during initial weeks of conception for vaginal bleeding. This may point towards etiology of the lesion. PMID:26064805

  9. Appendicitis in a Child due to Streptococcus Pneumoniae: A Rare Case Report.

    PubMed

    Ghadage, Dnyaneshawari Purushottam; Kamble, Deepali Shivajirao; Nale, Swati Shivajirao; Bhore, Arvind Vamanrao

    2015-01-01

    A variety of bacterial species play a major role in appendicitis. Both aerobic and anaerobic gram positive and gram negative bacteria such as, Bacteroides fragilis, Streptococcus species, Escherichia coli, Klebsiella species and Citrobacter freundii cause appendicitis. Appendicitis is usually polymicrobial. The case assumes importance because of single aetiological agent i.e. unimicrobial and no predisposing factors are present to cause infection. We report a rare case of appendicitis due to Streptococcus pneumoniae in child. This case emphasizes that Streptococcus pneumoniae can cause wide spectrum of disease like appendicitis. PMID:25737990

  10. Streptococcus pneumoniae NanC

    PubMed Central

    Owen, C. David; Lukacik, Petra; Potter, Jane A.; Sleator, Olivia; Taylor, Garry L.; Walsh, Martin A.

    2015-01-01

    Streptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from α2–3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-β-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind α2–3- and α2–6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold. PMID:26370075

  11. Molecular pathogenicity of Streptococcus anginosus.

    PubMed

    Asam, D; Spellerberg, B

    2014-08-01

    Streptococcus anginosus and the closely related species Streptococcus constellatus and Streptococcus intermedius, are primarily commensals of the mucosa. The true pathogenic potential of this group has been under-recognized for a long time because of difficulties in correct species identification as well as the commensal nature of these species. In recent years, streptococci of the S. anginosus group have been increasingly found as relevant microbial pathogens in abscesses and blood cultures and they play a pathogenic role in cystic fibrosis. Several international studies have shown a surprisingly high frequency of infections caused by the S. anginosus group. Recent studies and a genome-wide comparative analysis suggested the presence of multiple putative virulence factors that are well-known from other streptococcal species. However, very little is known about the molecular basis of pathogenicity in these bacteria. This review summarizes our current knowledge of pathogenicity factors and their regulation in S. anginosus. PMID:24848553

  12. Multilocus Sequence Analysis of Streptococcus canis Confirms the Zoonotic Origin of Human Infections and Reveals Genetic Exchange with Streptococcus dysgalactiae subsp. equisimilis

    PubMed Central

    Pinho, M. D.; Matos, S. C.; Pomba, C.; Lübke-Becker, A.; Wieler, L. H.; Preziuso, S.; Melo-Cristino, J.

    2013-01-01

    Streptococcus canis is an animal pathogen that occasionally causes human infections. Isolates recovered from infections of animals (n = 78, recovered from 2000 to 2010 in three European countries, mainly from house pets) and humans (n = 7, recovered from 2006 to 2010 in Portugal) were identified by phenotypic and genotypic methods and characterized by antimicrobial susceptibility testing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and emm typing. S. canis isolates presented considerable variability in biochemical profiles and 16S rRNA. Resistance to antimicrobial agents was low, with the most significant being tet(M)- and tet(O)-mediated tetracycline resistance. MLST analysis revealed a polyclonal structure of the S. canis population causing infections, where the same genetic lineages were found infecting house pets and humans and were disseminated in distinct geographic locations. Phylogenetic analysis indicated that S. canis was a divergent taxon of the sister species Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis and found evidence of acquisition of genetic material by S. canis from S. dysgalactiae subsp. equisimilis. PFGE confirmed the MLST findings, further strengthening the similarity between animal and human isolates. The presence of emm-like genes was restricted to a few isolates and correlated with some MLST-based genetic lineages, but none of the human isolates could be emm typed. Our data show that S. canis isolates recovered from house pets and humans constitute a single population and demonstrate that isolates belonging to the main genetic lineages identified have the ability to infect the human host, providing strong evidence for the zoonotic nature of S. canis infection. PMID:23345291

  13. Oral Pyogenic Granuloma Associated With a Dental Implant Treated With an Er:YAG Laser: A Case Report.

    PubMed

    Kaya, Alper; Ugurlu, Faysal; Basel, Bilal; Sener, Cem B

    2015-12-01

    A pyogenic granuloma is a tumorlike proliferation that occurs slightly more often in females, frequently involving the gingiva in the maxillary region. Clinically, it presents as a sessile or pedunculated exophytic mass with a smooth or lobulated surface, which tends to bleed easily. Its color can range from pink to dark red. The most common treatment is surgical excision. This case report presents a pyogenic granuloma that formed around an implant 7 years after its insertion. Pyogenic granulomas associated with dental implants are extremely rare; this is the fourth reported case and the first case of pyogenic granuloma to be treated with an Er:YAG laser. PMID:24351117

  14. Bacteriophage enzymes for the prevention and treatment of bacterial infections: Stability and stabilization of the enzyme lysing Streptococcus pyogenes cells

    SciTech Connect

    Klyachko, N. L.; Dmitrieva, N. F.; Eshchina, A. S.; Ignatenko, O. V.; Filatova, L. Y.; Rainina, Evguenia I.; Kazarov, A. K.; Levashov, A. V.

    2008-06-01

    Recombinant, phage associated lytic enzyme Ply C capable to lyse streptococci of groups A and C was stabilized in the variety of the micelles containing compositions to improve the stability of the enzyme for further application in medicine. It was shown that, in the micellar polyelectrolyte composition M16, the enzyme retained its activity for 2 months; while in a buffer solution under the same conditions ((pH 6.3, room temperature), it completely lost its activity in 2 days

  15. Effect of penicillin on surface carbohydrate, hemolysin and morphology of Streptococcus pyogenes during and after the post-antibiotic phase.

    PubMed

    Garcia, L B; Fonseca, M E; Benchetrit, L C

    2004-06-01

    The post-antibiotic effect (PAE) of penicillin was measured in vitro against a group A streptococcal strain by the kinetic growth method. The duration of the effect was 2.8 h. The bacterial morphology and some streptococcal products were analyzed during and after the PAE, after being exposed to penicillin in a concentration of 1xMIC for 2 h. Bacteria not previously exposed to penicillin were used as a control culture. Morphological changes and increases in the size of treated streptococci were observed by electronic microscope during the post-antibiotic phase. The post-penicillin effect on the production of cell-bound hemolysin and free hemolysin was examined using sheep red blood cells. Production of cell-bound hemolysin rose sharply, but was inhibited by the antimicrobial agent. The free lysin diminished significantly, and concomitantly with a higher production of free toxin by the treated cells. No effect was observed on the specific carbohydrate group when the antigen was tested with streptococcal group A antiserum. PMID:15330318

  16. Associations of macrolide and fluoroquinolone resistance with molecular typing in Streptococcus pyogenes from invasive infections, 2010-2012.

    PubMed

    Wajima, Takeaki; Morozumi, Miyuki; Chiba, Naoko; Shouji, Michi; Iwata, Satoshi; Sakata, Hiroshi; Ubukata, Kimiko

    2013-11-01

    In this study, the relationship between emm type and antibiotic resistance in 283 invasive group A streptococcal strains collected during surveillance from 2010 to 2012 was analysed. Strains were characterised by emm typing, multilocus sequence typing and antimicrobial susceptibility. Resistance rates for macrolide antibiotics conferred by mef(A), erm(A) or erm(B) were high (54.4%). The most prevalent (40.3%) macrolide resistance mediated by mef(A) was present in 92.2% of emm1 strains. It was found that 53.3% of emm12 strains and 91.7% of emm28 strains had erm(A) or erm(B) genes. Intermediate resistance to fluoroquinolones caused by a mutation in parC was found in 14.1% of strains. Furthermore, three strains (1.1%) with high resistance caused by mutations in both parC and gyrA were detected. Fluoroquinolone resistance was present in various emm types. PMID:23988719

  17. Development of primer sets for loop-mediated isothermal amplification that enables rapid and specific detection of Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus agalactiae are the three main pathogens causing bovine mastitis, with great losses to the dairy industry. Rapid and specific loop-mediated isothermal amplification methods (LAMP) for identification and differentiation of these three ...

  18. Single-level lumbar pyogenic spondylodiscitis treated with mini-open anterior debridement and fusion in combination with posterior percutaneous fixation via a modified anterior lumbar interbody fusion approach.

    PubMed

    Lin, Yang; Li, Feng; Chen, Wenjian; Zeng, Heng; Chen, Anmin; Xiong, Wei

    2015-12-01

    OBJECT This study evaluated the efficacy and safety of mini-open anterior debridement and lumbar interbody fusion in combination with posterior percutaneous fixation for single-level lumbar pyogenic spondylodiscitis. METHODS This is a retrospective study. Twenty-two patients with single-level lumbar pyogenic spondylodiscitis underwent mini-open anterior debridement and lumbar interbody fusion in combination with posterior percutaneous fixation via a modified anterior lumbar interbody fusion (ALIF) approach. Patients underwent follow-up for 24 to 38 months. Clinical data, etiological examinations, operative time, intraoperative blood loss, American Spinal Injury Association (ASIA) grade, Japanese Orthopaedic Association (JOA) lumbar function score, visual analog scale (VAS) score, Oswestry Disability Index (ODI), postoperative complications, and the bony fusion rate were recorded. RESULTS The mean operative time was 181.1 22.6 minutes (range 155-240 minutes). The mean intraoperative blood loss was 173.2 70.1 ml (range 100-400 ml). Infection was found in lumbar vertebrae L2-3, L3-4, and L4-5 in 2, 6, and 14 patients, respectively. Bacterial cultures were positive in 15 patients, including 4 with Staphylococcus aureus, 6 with Staphylococcus epidermidis, 4 with Streptococcus, and 1 with Escherichia coli. Postoperative complications included urinary retention, constipation, and numbness in the thigh in 5, 3, and 2 patients, respectively. Compared with before surgery, the VAS scores and ODI were significantly lower at the final follow-up, the JOA scores were significantly higher, and the ASIA grades had improved. All patients achieved good intervertebral bony fusion. CONCLUSIONS Mini-open anterior debridement and lumbar interbody fusion in combination with posterior percutaneous fixation via a modified ALIF approach results in little surgical trauma and intraoperative blood loss, acceptable postoperative complications, and is effective and safe for the treatment of single-level lumbar pyogenic spondylodiscitis. This approach could be an alternative to the conventional open surgery. PMID:26340382

  19. Pyogenic Granuloma: Surgical Treatment with Er:YAG Laser

    PubMed Central

    Fekrazad, Reza; Nokhbatolfoghahaei, Hanieh; Khoei, Farzaneh; Kalhori, Katayoun AM

    2014-01-01

    Introduction: Pyogenic granuloma (PG) is a common tumor-like growth of the oral cavity, considered to be of non-neoplastic nature, often caused by constant low-grade trauma as well as poor oral hygiene and maybe due to hormonal disturbances. Surgical excision, and removal of underlying cause in some cases, is the preferred method of treatment as it is only a benign lesion.In order to remove this lesion, scalpel, cryosurgery and laser are used. Currently different lasers, with adequate parameters, are used for the surgery of PG, which include CO2 (Carbon Dioxide Laser), Nd:YAG (Neodymium-Doped Yttrium Aluminium Garnet), Diode and Er Family amongst others. In this present case, due to the proximity of the lesion with dental hard tissue, Er:YAG (Erbium-Doped Yttrium Aluminum Garnet) laser appears to be the more appropriate laser. The application of Laser is also a newly recommended technique. The aim of this study is to assess the stages of treatment, recovery and recurrence of PG when the Er:YAG laser is used. Furthermore this study aims to also evaluate the friendliness of this method with regards to the surgeon (therapist). Case report: A 24-year-old female was referred to the Laser Research Center of Dentistry of Tehran University of Medical Sciences with a complaint of gingival overgrowth and bleeding. This lesion was in the buccal and palatal side of the 5 and 6 maxillary teeth. Treatment plan included an excisional biopsy of the lesion using Er:YAG laser (3W, 300mJ, 10Hz, Short pulse, with contact headpiece). The bones were then cleaned of soft tissue before being smoothed using a curette. The excised specimen was preserved and sent for histopathological examination. Results: The patient reported no pain after surgery and did not use any systemic antibiotics. The patient was satisfied after the surgery. Chlorhexidine mouthwash was given to the patient. Pathology results confirmed Pyogenic granuloma.After 2 weeks, complete healing was observed. The 9-month follow-up was also carried out in order to check the process of healing as well as the recurrence. Conclusion: Excisional surgery is the preferred treatment method for PG. The application of laser can be considered as an effective and safe technique for excision of this lesion with minimal invasion and many clinical advantages such as less intra-operative bleeding, hemostasis and reduced pain and times of healing. PMID:25653822

  20. Tylosin Resistance in Arcanobacterium pyogenes Is Encoded by an Erm X Determinant

    PubMed Central

    Jost, B. Helen; Field, Adam C.; Trinh, Hien T.; Songer, J. Glenn; Billington, Stephen J.

    2003-01-01

    Arcanobacterium pyogenes, a commensal on the mucous membranes of many economically important animal species, is also a pathogen, causing abscesses of the skin, joints, and visceral organs as well as mastitis and abortion. In food animals, A. pyogenes is exposed to antimicrobial agents used for growth promotion, prophylaxis, and therapy, notably tylosin, a macrolide antibiotic used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Of 48 A. pyogenes isolates, 11 (22.9%) exhibited inducible or constitutive resistance to tylosin (MIC of ?128 ?g/ml). These isolates also exhibited resistance to other macrolide and lincosamide antibiotics, suggesting a macrolide-lincosamide resistance phenotype. Of the 11 resistant isolates, genomic DNA from nine hybridized to an erm(X)-specific probe. Cloning and nucleotide sequencing of the A. pyogenes erm(X) gene indicated that it was >95% similar to erm(X) genes from Corynebacterium and Propionibacterium spp. Eight of the erm(X)-containing A. pyogenes isolates exhibited inducible tylosin resistance, which was consistent with the presence of a putative leader peptide upstream of the erm(X) open reading frame. For at least one A. pyogenes isolate, 98-4277-2, erm(X) was present on a plasmid, pAP2, and was associated with the insertion sequence IS6100. pAP2 also carried genes encoding the repressor-regulated tetracycline efflux system determinant Tet 33. The repA gene from pAP2 was nonfunctional in Escherichia coli and at least one A. pyogenes isolate, suggesting that there may be host-encoded factors required for replication of this plasmid. PMID:14576111

  1. Tylosin resistance in Arcanobacterium pyogenes is encoded by an erm X determinant.

    PubMed

    Jost, B Helen; Field, Adam C; Trinh, Hien T; Songer, J Glenn; Billington, Stephen J

    2003-11-01

    Arcanobacterium pyogenes, a commensal on the mucous membranes of many economically important animal species, is also a pathogen, causing abscesses of the skin, joints, and visceral organs as well as mastitis and abortion. In food animals, A. pyogenes is exposed to antimicrobial agents used for growth promotion, prophylaxis, and therapy, notably tylosin, a macrolide antibiotic used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Of 48 A. pyogenes isolates, 11 (22.9%) exhibited inducible or constitutive resistance to tylosin (MIC of > or = 128 microg/ml). These isolates also exhibited resistance to other macrolide and lincosamide antibiotics, suggesting a macrolide-lincosamide resistance phenotype. Of the 11 resistant isolates, genomic DNA from nine hybridized to an erm(X)-specific probe. Cloning and nucleotide sequencing of the A. pyogenes erm(X) gene indicated that it was >95% similar to erm(X) genes from Corynebacterium and Propionibacterium spp. Eight of the erm(X)-containing A. pyogenes isolates exhibited inducible tylosin resistance, which was consistent with the presence of a putative leader peptide upstream of the erm(X) open reading frame. For at least one A. pyogenes isolate, 98-4277-2, erm(X) was present on a plasmid, pAP2, and was associated with the insertion sequence IS6100. pAP2 also carried genes encoding the repressor-regulated tetracycline efflux system determinant Tet 33. The repA gene from pAP2 was nonfunctional in Escherichia coli and at least one A. pyogenes isolate, suggesting that there may be host-encoded factors required for replication of this plasmid. PMID:14576111

  2. Phenotypic characteristics and virulence genotypes of Trueperella (Arcanobacterium) pyogenes strains isolated from European bison (Bison bonasus).

    PubMed

    Rzewuska, Magdalena; Stefańska, Ilona; Osińska, Barbara; Kizerwetter-Świda, Magdalena; Chrobak, Dorota; Kaba, Jarosław; Bielecki, Wojciech

    2012-11-01

    Trueperella (Arcanobacterium) pyogenes is an opportunistic animal pathogen, which in European bison is associated with different suppurative infections mainly of the urogenital tract. Little is known about the virulence of this bacterium and about the pathogenesis of infections. The main objective of this study was to determine phenotypic properties and virulence genotypes of the twenty-five T. pyogenes strains isolated from lesions in various tissues of free-living European bison. Classical bacteriological methods were used for phenotypic characterization. Genes encoding seven known and putative virulence factors of T. pyogenes were detected by PCR technique. Analysis of 16S rDNA partial sequences was performed to establish phylogenetic relationships of the isolated strains. All isolates showed typical morphological features of T. pyogenes and variable biochemical activity. Most of them displayed a strong positive effect in synergistic CAMP test. For all isolates the 16S rRNA gene partial sequence was identical to that of the T. pyogenes reference strain. All isolates carried the plo and fimA genes, while the nanH, nanP, cbpA, fimC and fimG genes were present in 40, 44, 12, 88 and 24% of the isolates, respectively. The T. pyogenes strains isolated from European bison represented various phenotypes and virulence genotypes, but there was no association between the investigated properties of the bacteria and the type of anatomopathological lesions from which they were isolated. These results indicate that the studied virulence factors of T. pyogenes are not significant determinants of the localization and type of infection caused by this bacterium. PMID:22658663

  3. Expression, genetic localization and phylogenic analysis of NAPlr in piscine Streptococcus dysgalactiae subspecies dysgalactiae isolates and their patterns of adherence

    PubMed Central

    Abdelsalam, M.; Fujino, M.; Eissa, A.E.; Chen, S.C.; Warda, M.

    2014-01-01

    Streptococcus dysgalactiae, the long recognized mammalian pathogen, has currently received a major concern regarding fish bacterial infection. Adhesion to host epithelial cells and the presence of wall-associated plasminogen binding proteins are prerequisites to Streptococcus infection. This is the first study of the occurrence of nephritis-associated plasminogen-binding receptor (NAPlr) and α-enolase genes in piscine S. dysgalactiae subspecies dysgalactiae (SDSD) isolates. Further characterization of surface localized NAPlr of fish SDSD revealed a similar immune-reactive band of 43 KDa as that from porcine S. dysgalactiae subsp. equisimilis (SDSE). The phylogenetic analysis revealed that NAPlr of fish SDSD is more associated with those of mammalian SDSE and Streptococcus pyogenes rather than of other streptococci. Our findings warrant public attention to the possible implication of these virulence genes in dissemination of SDSD to different tissues of infected hosts and to get advantage to new niches. The SDSD adherence patterns were also studied to better understand their pathogenicity. The patterns of adherence of SDSD on two different cell lines showed a different pattern of adherence. Such difference gives an insight about the variance in host susceptibility to infection. PMID:26425363

  4. Identification and Co-complex Structure of a New S. pyogenes SpeB Small Molecule Inhibitor.

    PubMed

    Wang, Ana Y; Gonzlez-Pez, Gonzalo E; Wolan, Dennis W

    2015-07-21

    The secreted Streptococcus pyogenes cysteine protease SpeB is implicated in host immune system evasion and bacterial virulence. We present a small molecule inhibitor of SpeB 2477 identified from a high-throughput screen based on the hydrolysis of a fluorogenic peptide substrate Ac-AIK-AMC. 2477 inhibits other SpeB-related proteases but not human caspase-3, suggesting that the molecule targets proteases with the papain-like structural fold. A 1.59 X-ray crystal structure of 2477 bound to the SpeB active site reveals the mechanism of inhibition and the essential constituents of 2477 necessary for binding. An assessment against a panel of 2477 derivatives confirms our structural findings and shows that a carbamate and nitrile on 2477 are required for SpeB inhibition, as these moieties provide an extensive network of electrostatic and hydrogen-bonding interactions with SpeB active site residues. Surprisingly, despite 2477 having a reduced inhibitory potential against papain, the majority of 2477-related compounds inhibit papain to a much greater and broader extent than SpeB. These findings indicate that SpeB is more stringently selective than papain for this panel of small molecule inhibitors. On the basis of our structural and biochemical characterization, we propose modifications to 2477 for subsequent rounds of inhibitor design that will impart specificity to SpeB over other papain-like proteases, including alterations of the compound to exploit the differences in CA protease active site pocket sizes and electrostatics. PMID:26132413

  5. Lysates of S. pyogenes serotype M49 induce pancreatic tumor growth delay by specific and unspecific antitumor immune responses.

    PubMed

    Linnebacher, Michael; Maletzki, Claudia; Emmrich, Jrg; Kreikemeyer, Bernd

    2008-10-01

    Treatment of pancreatic cancer by active unspecific bacterial immunotherapy is a promising new strategy. Recently, we showed that a single intratumoral injection of wildtype Streptococcus pyogenes M49 results in complete regression of pancreatic carcinoma in mice mediated both by unspecific cytotoxicity and by specific immune reactions against tumor cells. As for potential clinical use, conditioning and especially inactivation of bacteria would abolish the risk of systemic bacterial infections; we here explored the potential of a streptococcal lysate prepared by bacteriophage lysine to affect pancreatic carcinoma growth in vivo. Application of the lysate into established Panc02 tumors resulted in pronounced growth cessation accompanied by raises in levels of circulating monocytes, granulocytes, and natural killer cells. Detailed analysis of splenocyte subsets revealed lysate-induced transient increases in pre-B cells followed by raised levels of activated T cells. Moreover, blood levels of proinflammatory, T helper-1-type cytokines were significantly elevated. These systemic immunologic effects were accompanied by massive infiltrations of cytotoxic T cells into the tumors. Concomitantly, lymphocytes obtained from treated mice specifically recognized Panc02 tumor cells in IFN-gamma-enzyme-linked immunosorbent spot and in cellular cytotoxicity assays. In rechallenge experiments, these immunologic effector cells were found to delay, but not completely prevent growth of secondary tumors. However, when considering the notoriously depressed immune status of individuals suffering from pancreatic carcinoma, the orchestrated antitumoral immune responses we analyzed here in detail significantly strengthen the potential usefulness of microbial compounds as active unspecific immunotherapeutic agent for treatment of pancreatic carcinoma. PMID:18779749

  6. 78 FR 35155 - Establishing a List of Qualifying Pathogens Under the Food and Drug Administration Safety and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-12

    ...-tuberculous mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus agalactiae, S... aureus O. Streptococcus agalactiae P. Streptococcus pneumoniae Q. Streptococcus pyogenes R. Vibrio... species, Staphylococcus aureus, Streptococcus agalactiae, S. pneumoniae, S. pyogenes, and Vibrio...

  7. Streptococcus intermedius Bacteremia and Liver Abscess following a Routine Dental Cleaning.

    PubMed

    Livingston, Lachara V; Perez-Colon, Elimarys

    2014-01-01

    Streptococcus intermedius is a member of the Streptococcus anginosus group of bacteria. This group is part of the normal flora of the oropharynx, genitourinary, and gastrointestinal tracts; however, they have been known to cause a variety of purulent infections including meningitis, endocarditis, and abscesses, even in immunocompetent hosts. In particular, S. intermedius has been associated with the development of liver and brain abscesses. There have been several case reports of S. intermedius liver abscesses with active periodontal infection. To our knowledge, however, there has not been a case following a routine dental procedure. In fact, the development of liver abscesses secondary to dental procedures is very rare in general, and there are only a few case reports in the literature describing this in relation to any pathogen. We present a rare case of S. intermedius bacteremia and liver abscess following a dental cleaning. This case serves to further emphasize that even routine dental procedures can place a patient at risk of the development of bacteremia and liver abscesses. For this reason, the clinician must be sure to perform a detailed history and careful examination. Timely diagnosis of pyogenic liver abscesses is vital, as they are typically fatal if left untreated. PMID:25197585

  8. Group A Streptococcus tissue invasion by CD44-mediated cell signalling

    NASA Astrophysics Data System (ADS)

    Cywes, Colette; Wessels, Michael R.

    2001-12-01

    Streptococcus pyogenes (also known as group A Streptococcus, GAS), the agent of streptococcal sore throat and invasive soft-tissue infections, attaches to human pharyngeal or skin epithelial cells through specific recognition of its hyaluronic acid capsular polysaccharide by the hyaluronic-acid-binding protein CD44 (refs 1, 2). Because ligation of CD44 by hyaluronic acid can induce epithelial cell movement on extracellular matrix, we investigated whether molecular mimicry by the GAS hyaluronic acid capsule might induce similar cellular responses. Here we show that CD44-dependent GAS binding to polarized monolayers of human keratinocytes induced marked cytoskeletal rearrangements manifested by membrane ruffling and disruption of intercellular junctions. Transduction of the signal induced by GAS binding to CD44 on the keratinocyte surface involved Rac1 and the cytoskeleton linker protein ezrin, as well as tyrosine phosphorylation of cellular proteins. Studies of bacterial translocation in two models of human skin indicated that cell signalling triggered by interaction of the GAS capsule with CD44 opened intercellular junctions and promoted tissue penetration by GAS through a paracellular route. These results support a model of host cytoskeleton manipulation and tissue invasion by an extracellular bacterial pathogen.

  9. Comparative Genomics of the Bacterial Genus Streptococcus Illuminates Evolutionary Implications of Species Groups

    PubMed Central

    Gao, Xiao-Yang; Zhi, Xiao-Yang; Li, Hong-Wei; Klenk, Hans-Peter; Li, Wen-Jun

    2014-01-01

    Members of the genus Streptococcus within the phylum Firmicutes are among the most diverse and significant zoonotic pathogens. This genus has gone through considerable taxonomic revision due to increasing improvements of chemotaxonomic approaches, DNA hybridization and 16S rRNA gene sequencing. It is proposed to place the majority of streptococci into species groups. However, the evolutionary implications of species groups are not clear presently. We use comparative genomic approaches to yield a better understanding of the evolution of Streptococcus through genome dynamics, population structure, phylogenies and virulence factor distribution of species groups. Genome dynamics analyses indicate that the pan-genome size increases with the addition of newly sequenced strains, while the core genome size decreases with sequential addition at the genus level and species group level. Population structure analysis reveals two distinct lineages, one including Pyogenic, Bovis, Mutans and Salivarius groups, and the other including Mitis, Anginosus and Unknown groups. Phylogenetic dendrograms show that species within the same species group cluster together, and infer two main clades in accordance with population structure analysis. Distribution of streptococcal virulence factors has no obvious patterns among the species groups; however, the evolution of some common virulence factors is congruous with the evolution of species groups, according to phylogenetic inference. We suggest that the proposed streptococcal species groups are reasonable from the viewpoints of comparative genomics; evolution of the genus is congruent with the individual evolutionary trajectories of different species groups. PMID:24977706

  10. Streptococcus intermedius Bacteremia and Liver Abscess following a Routine Dental Cleaning

    PubMed Central

    Livingston, Lachara V.; Perez-Colon, Elimarys

    2014-01-01

    Streptococcus intermedius is a member of the Streptococcus anginosus group of bacteria. This group is part of the normal flora of the oropharynx, genitourinary, and gastrointestinal tracts; however, they have been known to cause a variety of purulent infections including meningitis, endocarditis, and abscesses, even in immunocompetent hosts. In particular, S. intermedius has been associated with the development of liver and brain abscesses. There have been several case reports of S. intermedius liver abscesses with active periodontal infection. To our knowledge, however, there has not been a case following a routine dental procedure. In fact, the development of liver abscesses secondary to dental procedures is very rare in general, and there are only a few case reports in the literature describing this in relation to any pathogen. We present a rare case of S. intermedius bacteremia and liver abscess following a dental cleaning. This case serves to further emphasize that even routine dental procedures can place a patient at risk of the development of bacteremia and liver abscesses. For this reason, the clinician must be sure to perform a detailed history and careful examination. Timely diagnosis of pyogenic liver abscesses is vital, as they are typically fatal if left untreated. PMID:25197585

  11. Competence for Natural Genetic Transformation in the Streptococcus bovis Group Streptococci S. infantarius and S. macedonicus

    PubMed Central

    Gudon, Eric; Renault, Pierre

    2013-01-01

    Natural genetic transformation is common among many species of the genus Streptococcus, but it has never, or rarely, been reported for the Streptococcus pyogenes and S. bovis groups of species, even though many streptococcal competence genes and the competence regulators SigX, ComR, and ComS are well conserved in both groups. To explore the incidence of competence in the S. bovis group, 25 isolates of S. infantarius and S. macedonicus were surveyed by employing culture in chemically defined media devoid of peptide nutrients and treatment with synthetic candidate pheromone peptides predicted from the sequence of the gene comS. Approximately half of strains examined were transformable, many transforming at high rates comparable to those for the well-characterized streptococcal natural transformation systems. In S. infantarius, nanomolar amounts of the synthetic pheromone LTAWWGL induced robust but transient competence in high-density cultures, but mutation of the ComRS locus abolished transformation. We conclude that at least these two species of the S. bovis group retain a robust system of natural transformation regulated by a ComRS pheromone circuit and the alternative sigma factor SigX and infer that transformation is even more common among the streptococci than has been recognized. The tools presented here will facilitate targeted genetic manipulation in this group of streptococci. PMID:23543718

  12. Macedocin, a Food-Grade Lantibiotic Produced by Streptococcus macedonicus ACA-DC 198

    PubMed Central

    Georgalaki, Marina D.; Van den Berghe, Erika; Kritikos, Dimitrios; Devreese, Bart; Van Beeumen, Jozef; Kalantzopoulos, George; De Vuyst, Luc; Tsakalidou, Effie

    2002-01-01

    Streptococcus macedonicus ACA-DC 198, a strain isolated from Greek Kasseri cheese, produces a food-grade lantibiotic named macedocin. Macedocin has a molecular mass of 2,794.76 ± 0.42 Da, as determined by electrospray mass spectrometry. Partial N-terminal sequence analysis revealed 22 amino acid residues that correspond with the amino acid sequence of the lantibiotics SA-FF22 and SA-M49, both of which were isolated from the pathogen Streptococcus pyogenes. Macedocin inhibits a broad spectrum of lactic acid bacteria, as well as several food spoilage and pathogenic bacteria, including Clostridium tyrobutyricum. It displays a bactericidal effect towards the most sensitive indicator strain, Lactobacillus sakei subsp. sakei LMG 13558T, while the producer strain itself displays autoinhibition when it is grown under conditions that do not favor bacteriocin production. Macedocin is active at pHs between 4.0 and 9.0, and it retains activity even after incubation for 20 min at 121°C with 1 atm of overpressure. Inhibition of macedocin by proteolytic enzymes is variable. PMID:12450808

  13. Streptococcus thermophilus CRISPR-Cas9 Systems Enable Specific Editing of the Human Genome.

    PubMed

    Müller, Maximilian; Lee, Ciaran M; Gasiunas, Giedrius; Davis, Timothy H; Cradick, Thomas J; Siksnys, Virginijus; Bao, Gang; Cathomen, Toni; Mussolino, Claudio

    2016-03-01

    RNA-guided nucleases (RGNs) based on the type II CRISPR-Cas9 system of Streptococcus pyogenes (Sp) have been widely used for genome editing in experimental models. However, the nontrivial level of off-target activity reported in several human cells may hamper clinical translation. RGN specificity depends on both the guide RNA (gRNA) and the protospacer adjacent motif (PAM) recognized by the Cas9 protein. We hypothesized that more stringent PAM requirements reduce the occurrence of off-target mutagenesis. To test this postulation, we generated RGNs based on two Streptococcus thermophilus (St) Cas9 proteins, which recognize longer PAMs, and performed a side-by-side comparison of the three RGN systems targeted to matching sites in two endogenous human loci, PRKDC and CARD11. Our results demonstrate that in samples with comparable on-target cleavage activities, significantly lower off-target mutagenesis was detected using St-based RGNs as compared to the standard Sp-RGNs. Moreover, similarly to SpCas9, the StCas9 proteins accepted truncated gRNAs, suggesting that the specificities of St-based RGNs can be further improved. In conclusion, our results show that Cas9 proteins with longer or more restrictive PAM requirements provide a safe alternative to SpCas9-based RGNs and hence a valuable option for future human gene therapy applications. PMID:26658966

  14. Genomic organization and molecular characterization of SM1, a temperate bacteriophage of Streptococcus mitis.

    PubMed

    Siboo, Ian R; Bensing, Barbara A; Sullam, Paul M

    2003-12-01

    The direct binding of Streptococcus mitis to human platelets is mediated in part by two proteins (PblA and PblB) encoded by a lysogenic bacteriophage (SM1). Since SM1 is the first prophage of S. mitis that has been identified and because of the possible role of these phage-encoded proteins in virulence, we sought to characterize SM1 in greater detail. Sequencing of the SM1 genome revealed that it consisted of 34,692 bp, with an overall G+C content of 39 mol%. Fifty-six genes encoding proteins of 40 or more amino acids were identified. The genes of SM1 appear to be arranged in a modular, life cycle-specific organization. BLAST analysis also revealed that the proteins of SM1 have homologies to proteins from a wide variety of lambdoid phages. Bioinformatic analyses, in addition to N-terminal sequencing of the proteins, led to the assignment of possible functions to a number of proteins, including the integrase, the terminase, and two major structural proteins. Examination of the phage structural components indicates that the phage head may assemble using stable multimers of the major capsid protein, in a process similar to that of phage r1t. These findings indicate that SM1 may be part of a discrete subfamily of the Siphoviridae that includes at least phages r1t of Lactococcus lactis and SF370.3 of Streptococcus pyogenes. PMID:14617660

  15. Recombination-deficient Streptococcus sanguis

    SciTech Connect

    Daneo-Moore, L.; Volpe, A.

    1985-05-01

    A UV-sensitive derivative was obtained from Streptococcus sanguis Challis. The organism could be transformed with a number of small streptococcal plasmids at frequencies equal to, or 1 logarithm below, the transformation frequencies for the parent organism. However, transformation with chromosomal DNA was greatly impaired in the UV-sensitive derivative.

  16. Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children.

    PubMed

    Azzari, Chiara; Moriondo, Maria; Indolfi, Giuseppe; Massai, Cristina; Becciolini, Laura; de Martino, Maurizio; Resti, Massimo

    2008-10-01

    The aims of this study were to evaluate the incidence of invasive pneumococcal disease (IPD) in Italian children and perform serotyping by PCR-based assays directly on clinical samples. A 1-year paediatric (0-14 years) population-based surveillance study was designed to evaluate the incidence of IPD in the province of Florence, Italy, by cultural and molecular methods. Among 92 children (80 with pneumonia, 8 with meningitis/sepsis, 4 with arthritis), 4 cases of IPD were diagnosed both by culture and real-time PCR and 18 cases exclusively by molecular methods. The sensitivity of molecular methods was significantly higher than that of cultural methods (Cohen's kappa 0.41; McNemar P=0.000008). The incidence of IPD in children below 2 years of age was 11.5/100,000 and 51.8/100,000 by cultural and molecular methods, respectively. Pneumococcal serotyping by multiplex sequential PCR was obtained in 19/22 samples. Real-time PCR and multiplex sequential PCR can be used directly on biological samples, improving the ability to diagnose IPD. The incidence of IPD appears 5-10 times higher by PCR than by cultural methods. PMID:18809546

  17. The effect of ingestion of milk supplemented with salivaricin A-producing Streptococcus salivarius on the bacteriocin-like inhibitory activity of streptococcal populations on the tongue.

    PubMed

    Dierksen, Karen P; Moore, Chris J; Inglis, Megan; Wescombe, Philip A; Tagg, John R

    2007-03-01

    The colonization efficacies of salivaricin A (SalA)-producing Streptococcus salivarius strains 20P3 and 5 were compared when given in milk to 219 children, using either 2-day or 9-day dosing regimens. Colonization levels overall were superior for strain 5, and the 9-day dosing schedule resulted in higher levels of both initial colonization and strain persistence. The indigenous streptococcal tongue populations of 20 (10.9%) of the 189 children in the 2-day trial showed markedly increased SalA-like inhibitory activity following use of the S. salivarius-supplemented milk. All 20 of these children were found to have had relatively small (<5% of total S. salivarius) indigenous tongue populations of SalA-producing S. salivarius, and the relative proportions and/or inhibitory activity of these SalA producers on the childrens' tongues increased following ingestion of the S. salivarius-supplemented milk. Because SalA is known to be strongly inhibitory to Streptococcus pyogenes, an important implication of this study is that the consumption of SalA-producing probiotic S. salivarius could potentially help to effect a sustained increase in SalA-mediated protection against S. pyogenes infection. PMID:17069620

  18. Genotypic characterization and evaluation of an antibiotic resistance of Trueperella pyogenes (Arcanobacterium pyogenes) isolated from milk of dairy cows with clinical mastitis.

    PubMed

    Zastempowska, Ewa; Lassa, Henryka

    2012-12-28

    Trueperella pyogenes, recently reclassified from the genus Arcanobacterium, is considered the causative agent of acute suppurative mastitis called summer mastitis. T. pyogenes produces a variety of known and putative virulence factors that include pyolysin and factors promoting adhesion to host cells. The objective of this study was to report the presence of virulence genes in T. pyogenes isolates that were identified as etiological agents of clinical mastitis in cows, as well as to determine antimicrobial resistance and distribution of selected determinants that can be associated with phenotypic resistance among these isolates. The presence of genes (plo, nanH, nanP, cbpA, fimA, fimC, fimE, fimG, tet(W), erm(X), erm(B)) was examined by conventional PCRs. Resistance to 10 antimicrobial agents was determined by the broth microdilution method. Among T. pyogenes isolates of bovine mastitis origin the genes encoding all virulence factors occurred. Besides pyolysin gene plo, the fimA was the only gene detected in all isolates, whereas other virulence factor genes were found with different frequencies. Phenotypic antimicrobial resistance was observed to tetracycline (85.5% isolates) and erythromycin (9.1%). Isolates non-susceptible to erythromycin simultaneously exhibited increased MIC of pirlimycin. Beta-lactams were active against isolates. We found the correlation between the presence of tetracycline and macrolide resistance genes and corresponding resistance phenotype. Genotypic characterization of a large number of T. pyogenes isolates from different herds performed in this study may be useful in explanation, which virulence factors play a significant role in the establishment of bovine mammary gland infection. PMID:22868181

  19. Staphylococcal endogenous endophthalmitis in association with pyogenic vertebral osteomyelitis.

    PubMed

    Steeples, L R; Jones, N P

    2016-01-01

    PurposeTo describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.MethodsA retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.ResultsOne patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.ConclusionsEndogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes. PMID:26449198

  20. Lumbar Aspergillus osteomyelitis mimicking pyogenic osteomyelitis in an immunocompetent adult.

    PubMed

    Yoon, Kyeong-Wook; Kim, Young-Jin

    2015-04-01

    Spinal Aspergillus osteomyelitis is rare and occurs mostly in immunocompromised patients, but especially very rare in immunocompetent adult. This report presents a case of lumbar vertebral osteomyelitis in immunocompetent adult. A 53-year-old male who had no significant medical history was admitted due to complaints of back pain radiating to the flank for the last 3 months, followed by a progressive motor weakness of both lower limbs. Lumbar magnetic resonance imaging (MRI) demonstrated osteomyelitis and diskitis, suspected to be a pyogenic condition rather than a tuberculosis infection. Despite antibiotic treatment for several weeks, the symptoms worsened, and finally, open surgery was performed. Surgical biopsy revealed an Aspergillus infection and medical treatment with amphotericin B was started. It can be diagnosed early through an MRI; biopsy is very important but difficult, and making the correct differential diagnosis is essential for avoiding unexpected complications. The authors report a case of lumbar Aspergillus osteomyelitis in an immunocompetent adult and reviewed previously described cases of spinal aspergillosis. PMID:25221965

  1. BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma.

    PubMed

    Groesser, Leopold; Peterhof, Eva; Evert, Matthias; Landthaler, Michael; Berneburg, Mark; Hafner, Christian

    2016-02-01

    Pyogenic granuloma (PG) is a common benign vascular skin lesion presenting as a rapidly growing angiomatous papule. The pathogenesis of most sporadic PGs and PGs associated with port wine stains (PWSs) remains elusive. We report that of 10 PGs secondarily arisen on a PWS, 8 showed a BRAF c.1799T>A (p.(Val600Glu)) and 1 a NRAS c.182A>G (p.(Gln61Arg)) mutation. The GNAQ c.548G>A mutation was identified in the PG and in the respective underlying PWS, indicating that PGs originate from cells of the PWS. In contrast to PG, 12 papulonodular lesions, which had developed in the PWSs of seven patients, showed a RAS and BRAF wild-type status. In sporadic PG we identified the BRAF c.1799T>A mutation in 3 of 25, a BRAF c.1391G>A mutation in 1 of 25, and a KRAS c.37G>C mutation in 1 of 25. Mutation-specific immunohistochemical detection of BRAF p.(Val600Glu) confirmed endothelial cells as carriers of the mutation in secondary and sporadic PG. Our study identifies the BRAF c.1799T>A mutation as a major driver mutation in the pathogenesis of, particularly, secondary PG. These data shed light on the hitherto undetermined genetic basis of PG and classify PG as a benign neoplasm. PMID:26802240

  2. Acute abdomen due to group A streptococcus bacteremia caused by an isolate with a mutation in the csrS gene.

    PubMed

    Kaneko, Masahiko; Maruta, Masaki; Shikata, Hisaharu; Hanayama, Masakazu; Ikebe, Tadayoshi

    2015-11-01

    Streptococcus pyogenes (group A streptococcus) is an aerobic gram-positive coccus that causes infections ranging from non-invasive pharyngitis to severely invasive necrotizing fasciitis. Mutations in csrS/csrR and rgg, negative regulator genes of group A streptococcus, are crucial factors in the pathogenesis of streptococcal toxic shock syndrome, which is a severe, invasive infection characterized by sudden onset of shock and multiorgan failure, resulting in a high mortality rate. Here we present a case of group A streptococcal bacteremia in a 28-year-old Japanese woman with no relevant previous medical history. The patient developed progressive abdominal symptoms that may have been due to spontaneous bacterial peritonitis, followed by a state of shock, which did not fulfill the proposed criteria for streptococcal toxic shock. The isolate was found to harbor a mutation in the negative regulator csrS gene, whereas the csrR and rgg genes were intact. It was noteworthy that this strain carrying a csrS mutation had caused group A streptococcal bacteremia characterized by acute abdomen as the presenting symptom in a young individual who had been previously healthy. This case indicates that group A streptococcus with csrS mutations has potential virulence factors that are associated with the onset of group A streptococcal bacteremia that does not meet the diagnostic criteria for streptococcal toxic shock syndrome. PMID:26231317

  3. Salivaricin D, a Novel Intrinsically Trypsin-Resistant Lantibiotic from Streptococcus salivarius 5M6c Isolated from a Healthy Infant

    PubMed Central

    Birri, Dagim Jirata; Brede, Dag Anders

    2012-01-01

    In this work, we purified and characterized a newly identified lantibiotic (salivaricin D) from Streptococcus salivarius 5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (salI) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogens Streptococcus pyogenes and Streptococcus pneumoniae. Thus, Streptococcus salivarius 5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium. PMID:22101034

  4. Salivaricin D, a novel intrinsically trypsin-resistant lantibiotic from Streptococcus salivarius 5M6c isolated from a healthy infant.

    PubMed

    Birri, Dagim Jirata; Brede, Dag Anders; Nes, Ingolf F

    2012-01-01

    In this work, we purified and characterized a newly identified lantibiotic (salivaricin D) from Streptococcus salivarius 5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (salI) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogens Streptococcus pyogenes and Streptococcus pneumoniae. Thus, Streptococcus salivarius 5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium. PMID:22101034

  5. Group B streptococcus - pregnancy

    MedlinePLUS

    ... PS, Baker CJ. Group B streptococcal infections. In: Cherry J, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 7th ed. Philadelphia, ...

  6. Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines.

    PubMed Central

    AlonsoDeVelasco, E; Verheul, A F; Verhoef, J; Snippe, H

    1995-01-01

    Although pneumococcal conjugate vaccines are close to being licensed, a more profound knowledge of the virulence factors responsible for the morbidity and mortality caused by Streptococcus pneumoniae is necessary. This review deals with the major structures of pneumococci involved in the pathogenesis of pneumococcal disease and their interference with the defense mechanisms of the host. It is well known that protection against S. pneumoniae is the result of phagocytosis of invading pathogens. For this process, complement and anticapsular polysaccharide antibodies are required. Besides, relatively recent experimental data suggest that protection is also mediated by the removal of disintegrating pneumococci and their degradation products (cell wall, pneumolysin). These structures seem to be major contributors to illness and death caused by pneumococci. An effective conjugate vaccine should therefore preferably include the capsular polysaccharide and at least one of these inflammatory factors. PMID:8531887

  7. Occupational exposure to Streptococcus suis type 2.

    PubMed Central

    Robertson, I. D.; Blackmore, D. K.

    1989-01-01

    Antibody titres to Streptococcus suis type 2 were measured with an enzyme linked immunosorbent assay (ELISA) in four occupational groups in New Zealand. No veterinary students, 9% of dairy farmers, 10% of meat inspectors and 21% of pig farmers were seropositive to S. suis type 2. The development of antibody to S. suis type 2 was associated with occupational contact with pigs or their meat products. Subclinical infection with S. suis type 2 appears to occur in humans and the antibody produced is of only short duration. The annual incidence of subclinical infection and seroconversion in pig farmers may approach 28%. Thus S. suis type 2 may be one of the most infectious potentially zoonotic agents present in New Zealand, although very rarely resulting in clinical disease. PMID:2776849

  8. Bacterial Virulence in the Moonlight: Multitasking Bacterial Moonlighting Proteins Are Virulence Determinants in Infectious Disease

    PubMed Central

    Henderson, Brian; Martin, Andrew

    2011-01-01

    Men may not be able to multitask, but it is emerging that proteins can. This capacity of proteins to exhibit more than one function is termed protein moonlighting, and, surprisingly, many highly conserved proteins involved in metabolic regulation or the cell stress response have a range of additional biological actions which are involved in bacterial virulence. This review highlights the multiple roles exhibited by a range of bacterial proteins, such as glycolytic and other metabolic enzymes and molecular chaperones, and the role that such moonlighting activity plays in the virulence characteristics of a number of important human pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Helicobacter pylori, and Mycobacterium tuberculosis. PMID:21646455

  9. Single and multiple pyogenic liver abscesses. Natural history, diagnosis and treatment, with emphasis on percutaneous drainage.

    PubMed

    McDonald, M I; Corey, G R; Gallis, H A; Durack, D T

    1984-09-01

    The presenting features, modes of treatment and clinical course were reviewed for 55 patients with pyogenic liver abscess, seen at Duke University Medical Center over a 15-year period. Thirty-three patients had a solitary abscess and 22 had multiple abscesses. Most patients were between the ages of 40 and 60 years. Males predominated, 2.4:1. Major underlying conditions included biliary tract disease, malignancy and colonic disease. Eight patients, each with a solitary abscess, had no identifiable underlying condition. Symptoms and signs were nonspecific: fever, chills, focal abdominal tenderness and hepatomegaly were common. A raised serum alkaline phosphatase level was the most consistent abnormal laboratory finding. CT with contrast enhancement, radioisotope scanning and ultrasonography all accurately defined solitary hepatic abscesses. However, CT scan was more successful than other imaging techniques in detecting multiple abscesses. In seven patients the diagnosis was made only at laparotomy. Overall, a diagnosis of liver abscess was made in 50 living patients (91%). Microorganisms were recovered from pus and/or blood cultures of 44 patients (80%). Most common were enteric gram-negative facultative rods, anaerobic gram-negative rods, and microaerophilic streptococci. Single abscesses were more likely than multiple abscesses to contain more than one organism. All patients received antibiotics; the choice of antibiotic does not appear to be critical provided the regimen has a broad spectrum including activity against anaerobes. Surgical or percutaneous drainage was successful when attempted in all patients with a single abscess, but the outcome was less favorable in those with multiple abscesses. Percutaneous drainage is currently replacing open operative drainage as the method of choice. Overall mortality in patients with single abscesses was 15% (5/33) and in those with multiple abscesses 41% (9/22). PMID:6472091

  10. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

    PubMed

    Sharma, Onkar; O'Seaghdha, Maghnus; Velarde, Jorge J; Wessels, Michael R

    2016-03-01

    A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS) has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase). When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO), and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase) that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells. PMID:26938870

  11. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus

    PubMed Central

    Sharma, Onkar; O’Seaghdha, Maghnus; Velarde, Jorge J.; Wessels, Michael R.

    2016-01-01

    A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS) has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase). When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO), and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase) that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells. PMID:26938870

  12. A Gray-purple Mass on the Floor of the Mouth: Gigantic Mucogingival Pyogenic Granuloma in a Teenage Patient

    PubMed Central

    Brunet-LLobet, Llus; Miranda-Rius, Jaume; Lahor-Soler, Eduard; Mrina, Ombeni; Nadal, Alfons

    2014-01-01

    Pyogenic granuloma is defined as a benign neoplasm of vascular phenotype. This case describes the clinical and histopathological features of a gigantic mucogingival pyogenic granuloma, in a 14-year-old healthy black boy. This exophytic gray-purple mass, related to a toothpick injury, had more than twelve-month evolution on the anterior mandible involving lingual area besides to the floor of the mouth pressing the right salivary duct. Conservative excision was performed, followed by uncomplicated healing with no recurrence in two years. The histopathological examination reported a pyogenic granuloma (lobular capillary haemangioma). The authors provide a discussion of the presurgical differential diagnosis of the lesion. This case report presents an extremely uncommon location of a gigantic pyogenic granuloma, involving mucogingival complex and affecting the salivary outflow. This clinical manuscript may shed light on the controversies about possible mechanisms inducing oral pyogenic granuloma. PMID:24987485

  13. Obstruction of the external auditory meatus secondary to a giant pyogenic granuloma.

    PubMed

    Rehman, Sooda; Loizou, Peter; Singh, Pranay Kumar

    2015-01-01

    Pyogenic granuloma is a benign lesion of the skin and mucosa commonly known to occur in the head and neck region. The current literature has not yet identified its occurrence within the conchal bowl, a condition that leads to obstruction of the external auditory meatus. We present the case of a 28-year-old man who presented with a history of 3-4?weeks of a rapidly enlarging pedunculated lesion within the conchal bowl of the right ear and conductive hearing loss. Initial management included excision under local anaesthesia. The histological report concluded that it was a pyogenic granuloma. Later, reoccurrence was treated with a more definitive excision under general anaesthesia. During follow-up, the operative site was seen to have healed by secondary intention without reoccurrence. Although a pyogenic granuloma within the conchal bowl is benign, early therapeutic excision is important for histological diagnosis as much as to relieve consequential secondary obstruction and conductive hearing loss. PMID:26643183

  14. Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess: A Case-Control Study in Taiwan.

    PubMed

    Liao, Kuan-Fu; Lin, Cheng-Li; Lai, Shih-Wei; Chen, Wen-Chi

    2015-08-01

    The purpose of this study was to explore the association between zolpidem use and pyogenic liver abscess in Taiwan.This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. We identified 1325 patients aged 20 to 84 years with the first-attack of pyogenic liver abscess as the cases, and 5082 patients without pyogenic liver abscess matched with sex, age, comorbidities, and index year of hospitalization for pyogenic liver abscess as the controls. Patients whose last remaining 1 tablet for zolpidem was noted ?7 days before the date of admission for pyogenic liver abscess were defined as current use of zolpidem. Patients whose last remaining 1 tablet for zolpidem was noted >7 days before the date of admission for pyogenic liver abscess were defined as late use of zolpidem. Patients who never received 1 prescription for zolpidem were defined as never use of zolpidem. A multivariable unconditional logistic regression model was used to measure the odds ratio (OR) and 95% confidence interval (CI) to explore the association between zolpidem use and pyogenic liver abscess.After adjustment for possible confounding variables, the adjusted OR of pyogenic liver abscess was 3.89 for patients with current use of zolpidem (95% CI 2.89, 5.23), when compared with those with never use of zolpidem. The adjusted OR decreased to 0.85 for those with late use of zolpidem (95% CI 0.70, 1.03), but without statistical significance.Current use of zolpidem is associated with the increased risk of pyogenic liver abscess. Physicians should take the risk of pyogenic liver abscess into account when prescribing zolpidem. PMID:26266369

  15. First Isolation of Streptococcus halichoeri and Streptococcus phocae from a Steller Sea Lion (Eumetopias jubatus) in South Korea.

    PubMed

    Lee, Kichan; Kim, Ji-Yeon; Jung, Suk Chan; Lee, Hee-Soo; Her, Moon; Chae, Chanhee

    2016-01-01

    Streptococcus species are emerging potential pathogens in marine mammals. Wereport the isolation and identification of Streptococcus halichoeri and Streptococcus phocae in a Steller sea lion (Eumetopias jubatus) in South Korea. PMID:26555114

  16. Counteractive Balancing of Transcriptome Expression Involving CodY and CovRS in Streptococcus pyogenes▿†

    PubMed Central

    Kreth, Jens; Chen, Zhiyun; Ferretti, Joseph; Malke, Horst

    2011-01-01

    Streptococcus pyogenes (group A streptococcus [GAS]) responds to environmental changes in a manner that results in an adaptive regulation of the transcriptome. The objective of the present study was to understand how two global transcriptional regulators, CodY and CovRS, coordinate the transcriptional network in S. pyogenes. Results from expression microarray data and quantitative reverse transcription-PCR (qRT-PCR) showed that the global regulator CodY controls the expression of about 250 genes, or about 17% of the genome of strain NZ131. Additionally, the codY gene was shown to be negatively autoregulated, with its protein binding directly to the promoter region with a CodY binding site. In further studies, the influence of codY, covRS, and codY-covRS mutations on gene expression was analyzed in growth phase-dependent conditions using C medium, reported to mimic nutritional abundance and famine conditions similar to those found during host GAS infection. Additional biological experiments of several virulence phenotypes, including pilin production, biofilm formation, and NAD glycohydrolase activity, demonstrated the role that both CodY and CovRS play in their regulation. Correlation analysis of the overall data revealed that, in exponentially growing cells, CodY and CovRS act in opposite directions, with CodY stimulating and CovRS repressing a substantial fraction of the core genome, including many virulence factors. This is the first report of counteractive balancing of transcriptome expression by global transcription regulators and provides important insight into how GAS modulates gene expression by integrating important extracellular and intracellular information. PMID:21705595

  17. [Clinical aspects of streptococcal and staphylococcal toxinic diseases].

    PubMed

    Floret, D

    2001-09-01

    Staphylococcus aureus and Streptococcus pyogenes produce a lot of toxins, some of them responsible for specific diseases. Staphylococcal food poisoning is due to ingestion of enterotoxin containing food. Seven toxins have been isolated so far. Generalized exfoliative syndrome is related to exfoliatin. Young children are particularly affected. The disease consists in a cutaneous exfoliation usually limited with a favourable outcome. The mucus membranes are not involved. The nose or pharynx are the most usual portal of entry. Staphylococcus aureus is not grown from the bullae. Severe extensive forms have been observed particularly in neonates (Ritter's disease). Bullous impetigo is also due to exfoliatin. It consists in the presence of a restricted number of cloudy bullae, from which staphylococcus can be grown. It is a mild disease with a favourable outcome within a few days. Scarlet fever is related to the streptococcal erythrogenic toxins. The classic form of the disease is presently rare. This disease may be related to staphylococcus as a complication of arthritis, osteomyelitis or wound super-infection. Bacteremia is usual. Staphylococcal scarlet fever is not related to exfoliatin as previously believed, but to enterotoxins or TSST-1, so it seems to be an abortive form of toxic shock syndrome. Toxic shock syndrome is defined as a multi organ failure syndrome with a rapid onset, fever, rash followed by desquamation, vomiting and diarrhea, hypotension, conjunctivitis and strawberry tongue. The disease is related to an infection or colonisation with a toxin (TSST-1) producing strain of Staphylococcus aureus. Enterotoxins (mainly C) may be involved. The disease may occur in childhood, sometimes after superinfection of varicella. The mortality is low (5%) and mainly due to ARDS or cardiac problems. Erythrogenic toxins produced by Streptococcus pyogenes are involved in a streptococcal form of toxic shock syndrome with a quite similar presentation. In most cases however, a cutaneous or soft tissue infection is at the origin. Necrotizing fasciitis complicating varicella is a classic cause in children. Bacteremia is often observed. The mortality rate is as high as 60%. The streptococcal strains involved in north america use to produce the toxin erythrogenic A, the european cases seem to be more related to strains secreting the B toxin with a dysregulation of the mechanisms which control the secretion of the toxin. Staphylococcus strains producing the Panton and Valentine leucocidin are responsible for chronic or relapsing furonculosis and above all for a very severe necrotizing pneumonia observed in children and young adults presenting as an acute respiratory distress syndrome with leucopenia, hemoptysis and shock carrying a heavy mortality rate. Besides these specific diseases, staphylococcal and streptococcal toxins may be involved in some syndromes of unknown origin, in which the intervention of superantigens seems very likely. Kawasaki syndrome is among them as strains producing staphylococcal and streptococcal toxins have been grown from patients with Kawasaki syndrome. In the same way, the intervention of toxins is suspected in the determination of sudden infant death syndrome and atopic eczema. PMID:11582925

  18. Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis.

    PubMed

    Keller, Lance E; Robinson, D Ashley; McDaniel, Larry S

    2016-01-01

    While significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule-independent protection has been limited by serotype replacement along with disease caused by nonencapsulatedStreptococcus pneumoniae(NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis. Genes for pneumococcal surface proteins replace the capsular polysaccharide (cps) locus in some NESp isolates, and these proteins aid in pneumococcal colonization and otitis media (OM). NESp strains have been isolated from patients with invasive and noninvasive pneumococcal disease, but noninvasive diseases, specifically, conjunctivitis (85%) and OM (8%), are of higher prevalence. Conjunctival strains are commonly of the so-called classical NESp lineages defined by multilocus sequence types (STs) ST344 and ST448, while sporadic NESp lineages such as ST1106 are more commonly isolated from patients with other diseases. Interestingly, sporadic lineages have significantly higher rates of recombination than classical lineages. Higher rates of recombination can lead to increased acquisition of antibiotic resistance and virulence factors, increasing the risk of disease and hindering treatment. NESp strains are a significant proportion of the pneumococcal population, can cause disease, and may be increasing in prevalence in the population due to effects on the pneumococcal niche caused by pneumococcal vaccines. Current vaccines are ineffective against NESp, and further research is necessary to develop vaccines effective against both encapsulated and nonencapsulated pneumococci. PMID:27006456

  19. Subcutaneous Immunization with Inactivated Bacterial Components and Purified Protein of Escherichia coli, Fusobacterium necrophorum and Trueperella pyogenes Prevents Puerperal Metritis in Holstein Dairy Cows

    PubMed Central

    Machado, Vinícius Silva; Bicalho, Marcela Luccas de Souza; Meira Junior, Enoch Brandão de Souza; Rossi, Rodolfo; Ribeiro, Bruno Leonardo; Lima, Svetlana; Santos, Thiago; Kussler, Arieli; Foditsch, Carla; Ganda, Erika Korzune; Oikonomou, Georgios; Cheong, Soon Hon; Gilbert, Robert Owen; Bicalho, Rodrigo Carvalho

    2014-01-01

    In this study we evaluate the efficacy of five vaccine formulations containing different combinations of proteins (FimH; leukotoxin, LKT; and pyolysin, PLO) and/or inactivated whole cells (Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes) in preventing postpartum uterine diseases. Inactivated whole cells were produced using two genetically distinct strains of each bacterial species (E. coli, F. necrophorum, and T. pyogenes). FimH and PLO subunits were produced using recombinant protein expression, and LKT was recovered from culturing a wild F. necrophorum strain. Three subcutaneous vaccines were formulated: Vaccine 1 was composed of inactivated bacterial whole cells and proteins; Vaccine 2 was composed of proteins only; and Vaccine 3 was composed of inactivated bacterial whole cells only. Two intravaginal vaccines were formulated: Vaccine 4 was composed of inactivated bacterial whole cells and proteins; and Vaccine 5 was composed of PLO and LKT. To evaluate vaccine efficacy, a randomized clinical trial was conducted at a commercial dairy farm; 371 spring heifers were allocated randomly into one of six different treatments groups: control, Vaccine 1, Vaccine 2, Vaccine 3, Vaccine 4 and Vaccine 5. Late pregnant heifers assigned to one of the vaccine groups were each vaccinated twice: at 230 and 260 days of pregnancy. When vaccines were evaluated grouped as subcutaneous and intravaginal, the subcutaneous ones were found to significantly reduce the incidence of puerperal metritis. Additionally, subcutaneous vaccination significantly reduced rectal temperature at 6±1 days in milk. Reproduction was improved for cows that received subcutaneous vaccines. In general, vaccination induced a significant increase in serum IgG titers against all antigens, with subcutaneous vaccination again being more effective. In conclusion, subcutaneous vaccination with inactivated bacterial components and/or protein subunits of E. coli, F. necrophorum and T. pyogenes can prevent puerperal metritis during the first lactation of dairy cows, leading to improved reproduction. PMID:24638139

  20. In Vitro Effect of Zingiber officinale Extract on Growth of Streptococcus mutans and Streptococcus sanguinis.

    PubMed

    Azizi, Arash; Aghayan, Shabnam; Zaker, Saeed; Shakeri, Mahdieh; Entezari, Navid; Lawaf, Shirin

    2015-01-01

    Background and Objectives. Tooth decay is an infectious disease of microbial origin. Considering the increasing prevalence of antibiotic resistance due to their overuse and also their side effects, medicinal plants are now considered for use against bacterial infections. This study aimed to assess the effects of different concentrations of Zingiber officinale extract on proliferation of Streptococcus mutans and Streptococcus sanguinis in vitro. Materials and Methods. In this experimental study, serial dilutions of the extract were prepared in two sets of 10 test tubes for each bacterium (total of 20). Standard amounts of bacterial suspension were added; 100? of each tube was cultured on prepared solid agar plates and incubated at 37C for 24 hours. Serial dilutions of the extract were prepared in another 20 tubes and 100? of each tube was added to blood agar culture medium while being prepared. The mixture was transferred to the plates. The bacteria were inoculated on plates and incubated as described. Results. The minimum inhibitory concentration (MIC) was 0.02?mg/mL for S. mutans and 0.3?mg/mL for S. sanguinis. The minimum bactericidal concentration (MBC) was 0.04?mg for S. mutans and 0.6?mg for S. sanguinis. Conclusion. Zingiber officinale extract has significant antibacterial activity against S. mutans and S. sanguinis cariogenic microorganisms. PMID:26347778

  1. In Vitro Effect of Zingiber officinale Extract on Growth of Streptococcus mutans and Streptococcus sanguinis

    PubMed Central

    Azizi, Arash; Aghayan, Shabnam; Zaker, Saeed; Shakeri, Mahdieh; Entezari, Navid; Lawaf, Shirin

    2015-01-01

    Background and Objectives. Tooth decay is an infectious disease of microbial origin. Considering the increasing prevalence of antibiotic resistance due to their overuse and also their side effects, medicinal plants are now considered for use against bacterial infections. This study aimed to assess the effects of different concentrations of Zingiber officinale extract on proliferation of Streptococcus mutans and Streptococcus sanguinis in vitro. Materials and Methods. In this experimental study, serial dilutions of the extract were prepared in two sets of 10 test tubes for each bacterium (total of 20). Standard amounts of bacterial suspension were added; 100ƛ of each tube was cultured on prepared solid agar plates and incubated at 37°C for 24 hours. Serial dilutions of the extract were prepared in another 20 tubes and 100ƛ of each tube was added to blood agar culture medium while being prepared. The mixture was transferred to the plates. The bacteria were inoculated on plates and incubated as described. Results. The minimum inhibitory concentration (MIC) was 0.02 mg/mL for S. mutans and 0.3 mg/mL for S. sanguinis. The minimum bactericidal concentration (MBC) was 0.04 mg for S. mutans and 0.6 mg for S. sanguinis. Conclusion. Zingiber officinale extract has significant antibacterial activity against S. mutans and S. sanguinis cariogenic microorganisms. PMID:26347778

  2. Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study.

    PubMed

    Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

    2016-01-01

    Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17-19.1] and increased number of deep CMBs [median (IQR), 3 (2-9) vs. 0 (0-1), p?=?0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R(2)?=?0.405; p?

  3. Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study

    PubMed Central

    Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P.; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

    2016-01-01

    Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17–19.1] and increased number of deep CMBs [median (IQR), 3 (2–9) vs. 0 (0–1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R2 = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke. PMID:26847666

  4. One-Stage Biopsy, Debridement, Reconstruction, and Stabilization of Pyogenic Vertebral Osteomyelitis

    PubMed Central

    Menon, Venugopal K.; Kumar, Kishore M.; Al Ghafri, Khalifa

    2014-01-01

    Study Design?Retrospective cohort study. Objective?To evaluate whether the proposed one-stage biopsy, culture, debridement, and reconstruction with stabilization strategy is a viable option for pyogenic vertebral osteomyelitis (PVO). PVO is increasing in frequency globally, particularly in immunologically compromised individuals. Typically, biopsy and culture sensitivity followed by staged surgery and long-term antibiotic therapy is the mainstay of therapy. Methods?This is a study of a group of 32 consecutive cases of PVO (spondylodiskitis) treated in our institution from 2010 to 2012. All cases had one-stage biopsy, culture sensitivity, debridement, reconstruction with iliac bone graft, and stabilization with titanium implants. The mean age in this series was 51 years, and the male-to-female ratio was 2.2:1. Approximately 50% of the patients had impaired immunity status. The commonest organism isolated was Pseudomonas aeruginosa. Culture-specific antibiotics were given for a minimum of 6 weeks to all patients. The follow-up period ranged from 6 months to a maximum of 2 years. All patients were assessed for wound healing, recurrence of infection, deformity progression, pain, and healing by radiologic and biochemical parameters. No generic or disease-specific outcome tools were used for this study. Results?All patients had good wound healing, although there was one case of superficial infection that was resolved with debridement. There were two implant failures with pseudarthrosis and one localized kyphosis in this series. Conclusions?The one-stage technique of biopsy, debridement, bone grafting, and stabilization can be recommended for most cases of PVO. PMID:25072003

  5. Is Streptococcus bovis a urinary pathogen?

    PubMed

    Matesanz, M; Rubal, D; Iiguez, I; Rabual, R; Garca-Garrote, F; Coira, A; Garca-Pas, M J; Pita, J; Rodriguez-Macias, A; Lpez-lvarez, M J; Alonso, M P; Corredoira, J

    2015-04-01

    The Streptococcus bovis group (SBG) comprises several microorganisms associated with human infections. They have been associated with bacteremia, endocarditis, biliary tract infection, meningitis, and colorectal cancer, but their role as urinary pathogens is not well known. The objective of this investigation was to discover the incidence and clinical significance of the bacteriuria associated with this complex. A retrospective analysis of all adult patients with bacteriuria caused by SBG during the period 1995-2012 was carried out. During the study period, SBG was isolated in 153 adult patients, who had a mean age of 67 years, most of them being women (80%). Most of our patients (65%) had some underlying disease, with urologic disease being the most common (37%), followed by diabetes mellitus (27%) and neurologic disease (25%). Among the 88 patients in whom we were able to correctly assess symptoms, 45% had asymptomatic bacteriuria, 35% had lower urinary tract infection, and 20% had upper urinary tract infection. In 14 cases (9%), SBG was also isolated in blood cultures. Most of the isolates of SBG (72%) were S. gallolyticus subsp. pasteurianus. All isolates were susceptible to penicillin, 98% to nitrofurantoin, and 77% to fosfomycin. Although SBG bacteriuria is uncommon, it should not always be taken as a contaminant, mainly when S. pasteurianus is isolated, because it may cause urinary tract infections and, occasionally, sepsis, whereas when S. gallolyticus is isolated from urine, it may be a marker of underlying endocarditis and colorectal cancer. PMID:25416160

  6. Pyogenic and non-pyogenic spinal infections: emphasis on diffusion-weighted imaging for the detection of abscesses and pus collections

    PubMed Central

    Kim, J; Capizzano, A A; Kirby, P; Kademian, J; Sato, Y

    2014-01-01

    The incidence of spinal infections has increased in the past two decades, owing to the increasing number of elderly patients, immunocompromised conditions, spinal surgery and instrumentation, vascular access and intravenous drug use. Conventional MRI is the gold standard for diagnostic imaging; however, there are still a significant number of misdiagnosed cases. Diffusion-weighted imaging (DWI) with a b-value of 1000 and apparent diffusion coefficient (ADC) maps provide early and accurate detection of abscess and pus collection. Pyogenic infections are classified into four types of extension based on MRI and DWI findings: (1) epidural/paraspinal abscess with spondylodiscitis, (2) epidural/paraspinal abscess with facet joint infection, (3) epidural/paraspinal abscess without concomitant spondylodiscitis or facet joint infection and (4) intradural abscess (subdural abscess, purulent meningitis and spinal cord abscess). DWI easily detects abscesses and demonstrates the extension, multiplicity and remote disseminated infection. DWI is often a key image in the differential diagnosis. Important differential diagnoses include epidural, subdural or subarachnoid haemorrhage, cerebrospinal fluid leak, disc herniation, synovial cyst, granulation tissue, intra- or extradural tumour and post-surgical fluid collections. DWI and the ADC values are affected by susceptibility artefacts, incomplete fat suppression and volume-averaging artefacts. Recognition of artefacts is essential when interpreting DWI of spinal and paraspinal infections. DWI is not only useful for the diagnosis but also for the treatment planning of pyogenic and non-pyogenic spinal infections. PMID:24999081

  7. Ribosomal mutations in Arcanobacterium pyogenes confer a unique spectrum of macrolide resistance.

    PubMed

    Jost, B Helen; Trinh, Hien T; Songer, J Glenn; Billington, Stephen J

    2004-03-01

    Four macrolide-resistant Arcanobacterium pyogenes isolates contained A2058T, A2058G, or C2611G (Escherichia coli numbering) mutations in their 23S rRNA genes. While these mutations conferred resistance to erythromycin, oleandomycin, and spiramycin, they did not confer resistance to tylosin. PMID:14982799

  8. Ribosomal Mutations in Arcanobacterium pyogenes Confer a Unique Spectrum of Macrolide Resistance

    PubMed Central

    Jost, B. Helen; Trinh, Hien T.; Songer, J. Glenn; Billington, Stephen J.

    2004-01-01

    Four macrolide-resistant Arcanobacterium pyogenes isolates contained A2058T, A2058G, or C2611G (Escherichia coli numbering) mutations in their 23S rRNA genes. While these mutations conferred resistance to erythromycin, oleandomycin, and spiramycin, they did not confer resistance to tylosin. PMID:14982799

  9. Sensitive and rapid detection of Trueperella pyogenes using loop-mediated isothermal amplification method.

    PubMed

    Zhang, Wenlong; Meng, Xiangli; Wang, Junwei

    2013-05-01

    Here we report the design and evaluation of a loop-mediated isothermal amplification (LAMP) assay for detecting Trueperella pyogenes DNA based on the plo gene sequence that encodes pyolysin. The results showed that target DNA was amplified specifically and with a detection limit 100-fold greater than PCR. PMID:23517678

  10. Complete Genome Sequence of Trueperella pyogenes, an Important Opportunistic Pathogen of Livestock

    PubMed Central

    Machado, Vinicius S.

    2014-01-01

    Here, we report the complete genome sequence of Trueperella pyogenes TP6375, a strain isolated from the uterus of a dairy cow affected with metritis. The complete circular genome is 2,338,390 bp and contains several genes needed for pathogenicity. PMID:24786956

  11. Multiple Pyogenic Granulomas After Burns: Response to Conservative Treatment in Five Children.

    PubMed

    Zhao, Hongliang; Zhao, Huanjun; Zhang, Cuiping; Fu, Xiaobing

    2015-01-01

    We describe five children with multiple pyogenic granulomas after burns that were healed effectively using conservative treatment consisting of 1% povidone-iodine, silver nanoparticle dressing, and antibiotics. No relapse of the lesions was observed from 6months to 2years later. PMID:25895011

  12. Nationwide surveillance of 6 otorhinolaryngological infectious diseases and antimicrobial susceptibility pattern in the isolated pathogens in Japan.

    PubMed

    Suzuki, Kenji; Kurono, Yuichi; Ikeda, Katsuhisa; Watanabe, Akira; Iwamoto, Aikichi; Totsuka, Kyoichi; Kaku, Mitsuo; Iwata, Satoshi; Kadota, Jun-ichi; Hanaki, Hideaki

    2015-07-01

    The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee has conducted a nationwide surveillance on antimicrobial susceptibility patterns and rates of isolation in 6 otolaryngological diseases. The surveillance program was conducted in the otorhinolaryngological departments of 29 universities, and their 26 affiliated hospitals. Patients suffering from acute otitis media, chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess between January 2011 and June 2012 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the drug susceptibility of detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria (Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus), three gram-negative bacteria (Haemophilus influenzae, Moraxella Catarrhalis, and Pseudomonas aeruginosa), and three anaerobic bacteria (Peptostreptococcus spp., Prevotella spp., and Fusobacterium spp.). Bacterial susceptibility to 39 antimicrobial drugs was investigated. We compared bacterial isolation ratio of each disease in this surveillance from those of past 4 times surveillance which we performed formerly, and we also compared percentage of main drug resistant strains from those of past 4 times surveillance. The age composition between this time and former surveillances was not statistically significant by student-t test. We were unable to completely resolve the rise in resistant bacteria, such as methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae, penicillin-intermediate resistant S. pneumoniae, beta-lactamase non-producing ampicillin-resistant H. influenzae, beta-lactamase producing ampicillin-resistant H. influenzae, and beta-lactamase producing amoxicillin clavulanic acid-resistant H. influenzae. We suggest promoting the proper usage of antimicrobial drugs in order to avoid the spread of these bacteria. PMID:26004175

  13. Macrolide resistance in Streptococcus species

    PubMed Central

    Ilakkiya, A.; Parveen, Shabana; Kumar, C. Naveen; Swathi, S.

    2015-01-01

    Background: The Streptococci are Gram-positive spherical bacteria (cocci) that characteristically form pairs and chains during growth. Some macrolide-resistant bacteria lack the proper receptor on the ribosome (through methylation of the rRNA). This may be under plasmid or chromosomal control. Aim and Objectives: The aim was to study the prevalence of macrolide resistance among the isolate and evaluate the degree of resistance by minimum inhibitory concentration (MIC) method. And also to detect the phenotypic pattern of macrolide resistance. Materials and Methods: All age group attending general medicine OPD and pediatric OPD with symptoms of respiratory and pyogenic infections are included in the study. Various samples are collected with detailed case history and processed for macrolide resistance among beta hemolytic Streptococci MIC method and D-test. Results: According to our studies resistance pattern in Group A Streptococci by D-test, cMLS was 27.85%, iMLS was 13.92%, M-type was 55.69%, in GCS, cMLS was 17.6%, M-type was 82.35% In GGS, cMLS was 31.58%, iMLS was 10.53% and M-type was 57.89%. Conclusions: Therefore by this study, we would like to highlight the necessity to do antibiotic sensitivity testing for all isolates, and limit the usage of antibiotics, whenever necessary and select the appropriate antibiotics for resistant strains. PMID:26015727

  14. Localised mitogenic activity in horses following infection with Streptococcus equi.

    PubMed

    McLean, R; Rash, N L; Robinson, C; Waller, A S; Paillot, R

    2015-06-01

    Streptococcus equi subspecies equi (S.?equi) is the causative agent of strangles, a highly contagious upper respiratory disease of equids. Streptococcus equi produces superantigens (sAgs), which are thought to contribute to strangles pathogenicity through non-specific T-cell activation and pro-inflammatory response. Streptococcus equi infection induces abscesses in the lymph nodes of the head and neck. In some individuals, some abscess material remains into the guttural pouch and inspissates over time to form chondroids which can harbour live S.?equi. The aim of this study was to determine the sites of sAg production during infection and therefore improve our understanding of their role. Abscess material, chondroids and serum collected from Equidae with signs of strangles were tested in mitogenic assays. Mitogenic sAg activity was only detected in abscess material and chondroids. Our data support the localised in vivo activity of sAg during both acute and carrier phases of S.?equi infection. PMID:25841794

  15. Streptococcus agalactiae mastitis: a review.

    PubMed Central

    Keefe, G P

    1997-01-01

    Streptococcus agalactiae continues to be a major cause of subclinical mastitis in dairy cattle and a source of economic loss for the industry. Veterinarians are often asked to provide information on herd level control and eradication of S. agalactiae mastitis. This review collects and collates relevant publications on the subject. The literature search was conducted in 1993 on the Agricola database. Articles related to S. agalactiae epidemiology, pathogen identification techniques, milk quality consequences, and control, prevention, and therapy were included. Streptococcus agalactiae is an oblique parasite of the bovine mammary gland and is susceptible to treatment with a variety of antibiotics. Despite this fact, where state or provincial census data are available, herd prevalence levels range from 11% (Alberta, 1991) to 47% (Vermont, 1985). Infection with S. agalactiae is associated with elevated somatic cell count and total bacteria count and a decrease in the quantity and quality of milk products produced. Bulk tank milk culture has, using traditional milk culture techniques, had a low sensitivity for identifying S. agalactiae at the herd level. New culture methods, using selective media and large inocula, have substantially improved the sensitivity of bulk tank culture. Efficacy of therapy on individual cows remains high. Protocols for therapy of all infected animals in a herd are generally successful in eradicating the pathogen from the herd, especially if they are followed up with good udder hygiene techniques. PMID:9220132

  16. High burden of invasive group A streptococcal disease in the Northern Territory of Australia.

    PubMed

    Boyd, R; Patel, M; Currie, B J; Holt, D C; Harris, T; Krause, V

    2016-04-01

    Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response. PMID:26364646

  17. RNA-mediated regulation in Gram-positive pathogens: an overview punctuated with examples from the group A Streptococcus

    PubMed Central

    Miller, Eric W.; Cao, Tram N.; Pflughoeft, Kathryn J.; Sumby, Paul

    2014-01-01

    RNA-based mechanisms of regulation represent a ubiquitous class of regulators that are associated with diverse processes including nutrient sensing, stress response, modulation of horizontal gene transfer, and virulence factor expression. While better studied in Gram-negative bacteria, the literature is replete with examples of the importance of RNA-mediated regulatory mechanisms to the virulence and fitness of Gram-positives. Regulatory RNAs are classified as cis-acting, e.g. riboswitches, which modulate the transcription, translation, or stability of co-transcribed RNA, or trans-acting, e.g. small regulatory RNAs, which target separate mRNAs or proteins. The group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive bacterial pathogen from which several regulatory RNA mechanisms have been characterized. The study of RNA-mediated regulation in GAS has uncovered novel concepts with respect to how small regulatory RNAs may positively regulate target mRNA stability, and to how CRISPR RNAs are processed from longer precursors. This review provides an overview of RNA-mediated regulation in Gram-positive bacteria, and is highlighted with specific examples from GAS research. The key roles that these systems play in regulating bacterial virulence are discussed and future perspectives outlined. PMID:25091277

  18. RNA-mediated regulation in Gram-positive pathogens: an overview punctuated with examples from the group A Streptococcus.

    PubMed

    Miller, Eric W; Cao, Tram N; Pflughoeft, Kathryn J; Sumby, Paul

    2014-10-01

    RNA-based mechanisms of regulation represent a ubiquitous class of regulators that are associated with diverse processes including nutrient sensing, stress response, modulation of horizontal gene transfer, and virulence factor expression. While better studied in Gram-negative bacteria, the literature is replete with examples of the importance of RNA-mediated regulatory mechanisms to the virulence and fitness of Gram-positives. Regulatory RNAs are classified as cis-acting, e.g. riboswitches, which modulate the transcription, translation, or stability of co-transcribed RNA, or trans-acting, e.g. small regulatory RNAs, which target separate mRNAs or proteins. The group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive bacterial pathogen from which several regulatory RNA mechanisms have been characterized. The study of RNA-mediated regulation in GAS has uncovered novel concepts with respect to how small regulatory RNAs may positively regulate target mRNA stability, and to how CRISPR RNAs are processed from longer precursors. This review provides an overview of RNA-mediated regulation in Gram-positive bacteria, and is highlighted with specific examples from GAS research. The key roles that these systems play in regulating bacterial virulence are discussed and future perspectives outlined. PMID:25091277

  19. Genotype, Phenotype, and Clinical Course in Five Patients With PAPA Syndrome (Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne)

    PubMed Central

    Demidowich, Andrew P.; Freeman, Alexandra F.; Kuhns, Douglas B.; Aksentijevich, Ivona; Gallin, John I.; Turner, Maria L.; Kastner, Daniel L.; Holland, Steven M.

    2013-01-01

    Objective To describe the genotypes, phenotypes, immunophenotypes, and treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), a rare autoinflammatory disease, in 5 patients. Methods Clinical information was gathered from medical records and through interviews with 5 patients from 4 kindreds. PSTPIP1 (CD2BP1) exon 10 and exon 11 sequencing was performed in each patient. Neutrophil granule content and cytokine levels were determined in plasma and stimulated peripheral blood mononuclear cells (PBMCs) from patients and controls. Results We identified 2 previously described PAPA syndrome–associated PSTPIP1 mutations, A230T and E250Q, and a novel change, E250K. Disease penetrance was incomplete, with variable expressivity. The cutaneous manifestations included pathergy, cystic acne, and pyoderma gangrenosum. Interleukin-1 (IL-1β) and circulating neutrophil granule enzyme levels were markedly elevated in patients compared to those in controls. PBMC stimulation studies demonstrated impaired production of IL-10 and enhanced production of granulocyte–macrophage colony-stimulating factor. Good resolution of pyoderma gangrenosum was achieved in 3 patients with tumor necrosis factor (TNFα) blockade treatment. Conclusion This analysis of 5 patients demonstrates that mutations in PSTPIP1 are incompletely penetrant and variably expressed in the PAPA syndrome. Neutrophil granule proteins are markedly elevated ex vivo and in the plasma, and elevated levels might be compatible with a diagnosis of PAPA syndrome. TNFα blockade appears to be effective in treating the cutaneous manifestations of PAPA syndrome. PMID:22161697

  20. Streptococcus ovis sp. nov., isolated from sheep.

    PubMed

    Collins, M D; Hutson, R A; Hoyles, L; Falsen, E; Nikolaitchouk, N; Foster, G

    2001-05-01

    Seven strains of an unknown Gram-positive catalase-negative chain-forming coccus-shaped organism isolated from clinical specimens from sheep were characterized by phenotypic and molecular taxonomic methods. Comparative 16S rRNA gene sequencing studies demonstrated that the bacterium represents a new sub-line within the genus Streptococcus. The unknown bacterium was readily distinguished from recognized streptococcal species by biochemical tests and electrophoretic analysis of whole-cell proteins. Based on phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Streptococcus ovis sp. nov. The type strain of Streptococcus ovis is CCUG 39485T (= LMG 19174T). PMID:11411683

  1. Penetration of Streptococcus sobrinus and Streptococcus sanguinis into dental enamel.

    PubMed

    Kneist, Susanne; Nietzsche, Sandor; Kpper, Harald; Raser, Gerhard; Willershausen, Brita; Callaway, Angelika

    2015-10-01

    The aim of this pilot study was to assess the difference in virulence of acidogenic and aciduric oral streptococci in an invitro caries model using their penetration depths into dental enamel. 30 caries-free extracted molars from 11- to 16-year-olds were cleaned ultrasonically for 1min with de-ionized water and, after air-drying, embedded in epoxy resin. After 8-h of setting at room temperature, the specimens were ground on the buccal side with SiC-paper 1200 (particle size 13-16?m). Enamel was removed in circular areas sized 3mm in diameter; the mean depth of removed enamel was 23060?m. 15 specimens each were incubated anaerobically under standardized conditions with 24h-cultures of Streptococcus sanguinis 9S or Streptococcus sobrinus OMZ 176 in Balmelli broth at 372C; the pH-values of the broths were measured at the beginning and end of each incubation cycle. After 2, 4, 6, 8, and 10 weeks 3 teeth each were fixed in 2.5% glutaraldehyde in cacodylate buffer for 24h, washed 3 and dehydrated 30-60min by sequential washes through a series of 30-100% graded ethanol. The teeth were cut in half longitudinally; afterward, two slits were made to obtain fracture surfaces in the infected area. After critical-point-drying the fragments were gold-sputtered and viewed in a scanning electron microscope at magnifications of20-20,000. After 10 weeks of incubation, penetration of S.sanguinis of 11.1324.04?m below the break edges into the enamel was observed. The invasion of S.sobrinus reached depths of 87.5376.34?m. The difference was statistically significant (paired t test: p=0.033). The experimental penetration depths emphasize the importance of S.sanguinis versus S. sobrinus in the context of the extended ecological plaque hypothesis. PMID:25805186

  2. Widespread distribution of a tet W determinant among tetracycline-resistant isolates of the animal pathogen Arcanobacterium pyogenes.

    PubMed

    Billington, Stephen J; Songer, J Glenn; Jost, B Helen

    2002-05-01

    Tetracycline resistance is common among isolates of the animal commensal and opportunistic pathogen Arcanobacterium pyogenes. The tetracycline resistance determinant cloned from two bovine isolates of A. pyogenes was highly similar at the DNA level (92% identity) to the tet(W) gene, encoding a ribosomal protection tetracycline resistance protein, from the rumen bacterium Butyrivibrio fibrisolvens. The tet(W) gene was found in all 20 tetracycline-resistant isolates tested, indicating that it is a widely distributed determinant of tetracycline resistance in this organism. In 25% of tetracycline-resistant isolates, the tet(W) gene was associated with a mob gene, encoding a functional mobilization protein, and an origin of transfer, suggesting that the determinant may be transferable to other bacteria. In fact, low-frequency transfer of tet(W) was detected from mob+ A. pyogenes isolates to a tetracycline-sensitive A. pyogenes recipient. The mobile nature of this determinant and the presence of A. pyogenes in the gastrointestinal tract of cattle and pigs suggest that A. pyogenes may have inherited this determinant within the gastrointestinal tracts of these animals. PMID:11959557

  3. Widespread Distribution of a Tet W Determinant among Tetracycline-Resistant Isolates of the Animal Pathogen Arcanobacterium pyogenes

    PubMed Central

    Billington, Stephen J.; Songer, J. Glenn; Jost, B. Helen

    2002-01-01

    Tetracycline resistance is common among isolates of the animal commensal and opportunistic pathogen Arcanobacterium pyogenes. The tetracycline resistance determinant cloned from two bovine isolates of A. pyogenes was highly similar at the DNA level (92% identity) to the tet(W) gene, encoding a ribosomal protection tetracycline resistance protein, from the rumen bacterium Butyrivibrio fibrisolvens. The tet(W) gene was found in all 20 tetracycline-resistant isolates tested, indicating that it is a widely distributed determinant of tetracycline resistance in this organism. In 25% of tetracycline-resistant isolates, the tet(W) gene was associated with a mob gene, encoding a functional mobilization protein, and an origin of transfer, suggesting that the determinant may be transferable to other bacteria. In fact, low-frequency transfer of tet(W) was detected from mob+ A. pyogenes isolates to a tetracycline-sensitive A. pyogenes recipient. The mobile nature of this determinant and the presence of A. pyogenes in the gastrointestinal tract of cattle and pigs suggest that A. pyogenes may have inherited this determinant within the gastrointestinal tracts of these animals. PMID:11959557

  4. Structure-Informed Design of an Enzymatically Inactive Vaccine Component for Group A Streptococcus

    PubMed Central

    Henningham, Anna; Ericsson, Daniel J.; Langer, Karla; Casey, Lachlan W.; Jovcevski, Blagojce; Chhatwal, G. Singh; Aquilina, J. Andrew; Batzloff, Michael R.; Kobe, Bostjan; Walker, Mark J.

    2013-01-01

    ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) causes ~700 million human infections/year, resulting in >500,000 deaths. There is no commercial GAS vaccine available. The GAS surface protein arginine deiminase (ADI) protects mice against a lethal challenge. ADI is an enzyme that converts arginine to citrulline and ammonia. Administration of a GAS vaccine preparation containing wild-type ADI, a protein with inherent enzymatic activity, may present a safety risk. In an approach intended to maximize the vaccine safety of GAS ADI, X-ray crystallography and structural immunogenic epitope mapping were used to inform vaccine design. This study aimed to knock out ADI enzyme activity without disrupting the three-dimensional structure or the recognition of immunogenic epitopes. We determined the crystal structure of ADI at 2.5 resolution and used it to select a number of amino acid residues for mutagenesis to alanine (D166, E220, H275, D277, and C401). Each mutant protein displayed abrogated activity, and three of the mutant proteins (those with the D166A, H275A, and D277A mutations) possessed a secondary structure and oligomerization state equivalent to those of the wild type, produced high-titer antisera, and avoided disruption of B-cell epitopes of ADI. In addition, antisera raised against the D166A and D277A mutant proteins bound to the GAS cell surface. The inactivated D166A and D277A mutant ADIs are ideal for inclusion in a GAS vaccine preparation. There is no human ortholog of ADI, and we confirm that despite limited structural similarity in the active-site region to human peptidyl ADI 4 (PAD4), ADI does not functionally mimic PAD4 and antiserum raised against GAS ADI does not recognize human PAD4. PMID:23919999

  5. Immunoproteomic analysis of the antibody response obtained in tilapia following immunization with a Streptococcus iniae vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Streptococcus iniae is one of the most economically important Gram-positive pathogens in cultured fish species worldwide. Research has shown that vaccination is a tool that can be used in the prevention of streptococcal disease. The USDA-ARS patented S. iniae vaccine has been demonstrated to be ef...

  6. Identification and Epidemiology of Streptococcus iniae and S. agalactiae in tilapias Oreochromis spp.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite being known mainly as mammalian disease agents, Streptococcus iniae and S. agalactiae have become recognized as emerging pathogens of wild and cultured fish. The worldwide economic impact of S. iniae and S. agalactiae to the aquaculture industry is estimated in hundreds of millions annually...

  7. Streptococcus group C meningitis with cavernous sinus thrombosis

    PubMed Central

    Clarke, Mattew; Enuh, Hilary; Saverimuttu, Jessie; Nfonoyim, Jay

    2013-01-01

    Group C Streptococcus (GCS) is a rare cause of bacteremia in humans. It is mostly associated with zoonological infections. Although GCS can be part of the normal oral, skin, and genitourinary fora, an infection with this pathogen can be highly virulent, causing rapid, disseminating disease. With a mortality of about 25%, the poor prognosis is linked to the severity of illness and the high level of virulence of the organism. Only a few cases of GCS meningitis have been reported. We present the first case of GCS meningitis with caver