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1

Clonal basis for resurgence of serious Streptococcus pyogenes disease in the 1980s.  

PubMed

During the 1980s there was a resurgence of serious Streptococcus pyogenes infections with complications, including rheumatic fever, sepsis, severe soft-tissue invasion, and toxic-shock-like syndrome (TSLS). We have investigated the suggested association between expression of a scarlet fever toxin, SPE A, and systemic toxicity, and the possibility that a new highly virulent clone of S pyogenes has emerged and spread world wide. We studied serotype M1 strains, the serotype most commonly associated with serious complications. 19 isolates from patients with sepsis, with or without TSLS, and 48 from patients with uncomplicated pharyngitis or superficial skin infection were subjected to restriction-enzyme digestion and electrophoresis; 56 isolates (19 serious, 37 uncomplicated disease) were then examined by hybridisation to an speA gene probe. 17 (90%) of the 19 serious-disease isolates had a characteristic ("invasive", I) restriction-fragment profile and were positive for the speA gene. Significantly lower proportions of the isolates from patients with uncomplicated disease had the I profile (21/48 [44%]; p = 0.0035) and speA (20/37 [54%]; p less than 0.001). These findings suggest that the strains from patients with serious disease are a unique clone, which became the predominant cause of severe streptococcal infections in the United States and elsewhere in the late 1980s. PMID:1346879

Cleary, P P; Kaplan, E L; Handley, J P; Wlazlo, A; Kim, M H; Hauser, A R; Schlievert, P M

1992-02-29

2

Impact of immunization against SpyCEP during invasive disease with two streptococcal species: Streptococcus pyogenes and Streptococcus equi  

PubMed Central

Currently there is no licensed vaccine against the human pathogen Streptococcus pyogenes. The highly conserved IL-8 cleaving S. pyogenes cell envelope proteinase SpyCEP is surface expressed and is a potential vaccine candidate. A recombinant N-terminal part of SpyCEP (CEP) was expressed and purified. AntiCEP antibodies were found to neutralize the IL-8 cleaving activity of SpyCEP. CEP-immunized mice had reduced bacterial dissemination from focal S. pyogenes intramuscular infection and intranasal infection. We also identified a functional SpyCEP-homolog protease SeCEP, expressed by the equine pathogen Streptococcus equi, which was able to cleave both human and equine IL-8. CEP-immunized mice also demonstrated reduced bacterial dissemination from S. equi intramuscular infection. Therefore immunization against SpyCEP may provide protection against other streptococci species with homologous proteases.

Turner, Claire E.; Kurupati, Prathiba; Wiles, Siouxsie; Edwards, Robert J.; Sriskandan, Shiranee

2009-01-01

3

[Molecular characterization of Streptococcus pyogenes from invasive disease and streptococcal toxic shock syndrome episodes].  

PubMed

Streptococcus pyogenes causes a variety of common human diseases, including pharyngitis, scarlet fever and impetigo. Nevertheless, the past decades have witnessed a worldwide resurgence in invasive disease and streptococcal toxic shock syndrome (STSS). The objective of the present study is to evaluate the genetic diversity, virulence gene distribution (spe, sme and ssa genes) and susceptibility pattern of 10 S. pyogenes isolates causing invasive disease and STSS. The isolates were recovered from blood cultures of hospitalized patients at Hospital Santamarina and Nueva Clínica Chacabuco, Tandil, Buenos Aires, Argentina between 12/2000-04/2005. Two pulse field gel electrophoretic patterns predominated. The most frequent one included 5 characteristic isolates of emm1-T1 type, toxin gene profile speA, speB, speF, speG and smeZ. The second pattern included 2 characteristic isolates of emm3-TNT type (speB, speF, speG). The other 3 isolates corresponded to types emm49-TNT (speB, speC, speF, speG), emm75-T25 (speB, speF, speG) and emm83-TNT (speB, speF, speG, ssa, smeZ). All isolates were susceptible to penicillin, cefotaxime, erythromycin, clindamycin, chloramphenicol, tetracycline and rifampicin. The data from the present study demonstrated genetic diversity among the strains. Types emm1 and emm3 were prevalent in invasive disease. The empirical treatment with the combination of penicillin and clindamicin is still valid. PMID:20461293

Traverso, F; Sparo, M; Rubio, V; Sáez Nieto, J A

4

Novel Regulatory Small RNAs in Streptococcus pyogenes  

PubMed Central

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.

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

2013-01-01

5

Meningitis in a Girl with Recurrent Otitis Media Caused by Streptococcus pyogenes – Otitis Media Has to Be Treated Appropriately  

Microsoft Academic Search

Streptococcus pyogenes rarely causes meningitis. A recent increase in the incidence and severity of diseases due to S. pyogenes has been observed worldwide, without an apparent increase in the incidence of S. pyogenes meningitis. However, more recently severe and fulminant cases of S. pyogenes meningitis have been reported in the literature. This case report emphasizes the fact that S. pyogenes

K. Steppberger; I. Adams; J. Deutscher; H. Müller; W. Kiess

2001-01-01

6

Complete Genome of Acute Rheumatic Fever-Associated Serotype M5 Streptococcus pyogenes Strain Manfredo  

Microsoft Academic Search

Comparisons of the 1.84-Mb genome of serotype M5 Streptococcus pyogenes strain Manfredo with previously sequenced genomes emphasized the role of prophages in diversification of S. pyogenes and the close relationship between strain Manfredo and MGAS8232, another acute rheumatic fever-associated strain. Streptococcus pyogenes (alternatively referred to as group A Streptococcus) is responsible for diverse diseases in humans, including pharyngitis, toxic shock

Matthew T. G. Holden; Annabel Scott; Inna Cherevach; Tracey Chillingworth; Carol Churcher; Ann Cronin; Linda Dowd; Theresa Feltwell; Nancy Hamlin; Simon Holroyd; Kay Jagels; Sharon Moule; Karen Mungall; Michael A. Quail; Claire Price; Ester Rabbinowitsch; Sarah Sharp; Jason Skelton; Sally Whitehead; Bart G. Barrell; Michael Kehoe; Julian Parkhill

2007-01-01

7

The serotypes of Streptococcus pyogenes present in Britain during 1980-1990 and their association with disease  

Microsoft Academic Search

Summary. A total of 16 909 cultures of Streptococcus pyogenes (Lancefield group A) isolated in Britain during 1980-90 were examined for T- and M-protein antigens. One or other M antigen was detected in 92.6 % of the strains. The numbers of isolates of some serotypes, such as M3 and M12, did not show great variation from year-to-year, whereas there were

G. Colman; ASHA TANNA; ANDROULLA EFSTRATIOU; EWA T. GAWORZEWSKA

1993-01-01

8

Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes.  

PubMed

Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an approximately 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils. PMID:16088827

Edwards, Robert J; Taylor, Graham W; Ferguson, Melissa; Murray, Stephen; Rendell, Nigel; Wrigley, Amanda; Bai, Zhonghu; Boyle, Joseph; Finney, Simon J; Jones, Angus; Russell, Hugh H; Turner, Claire; Cohen, Jonathan; Faulkner, Lee; Sriskandan, Shiranee

2005-07-18

9

Rapid identification of Streptococcus pyogenes by flow cytometry  

Microsoft Academic Search

Flow cytometry combined with immunofluorescence ofStreptococcus pyogenes was used to assay bacteria suspended in buffer solution and in saliva derived from throat swabs of healthy volunteers. The method allowed the enumeration of as few as 5 × 103 and 5 × 104 CFU per milliliter of buffer and saliva respectively. Controls includingStreptococcus salivarius instead ofStreptococcus pyogenes or buffer instead of

E. Sahar; R. Lamed; I. Ofek

1983-01-01

10

Characterization of Streptococcus   pyogenes Isolated from Balanoposthitis Patients Presumably Transmitted by Penile-Oral Sexual Intercourse  

Microsoft Academic Search

Streptococcus pyogenes is indigenous to the human pharynx and causes acute pharyngitis. Balanoposthitis is an inflammatory disease of the glans\\u000a and the foreskin. However, balanoposthitis caused by S. pyogenes is not widely recognized as a sexually transmitted disease. In addition, bacteriological features of the isolates causing\\u000a balanoposthitis are unclear. The four S. pyogenes strains isolated from adult balanoposthitis were examined. We performed emm

Yukio Wakimoto; Masakado Matsumoto; Hideyuki Matsui; Yasue Kubota; Atsushi Okada; Masanori Isaka; Ichiro Tatsuno; Yasuhito Tanaka; Tadao Hasegawa

2010-01-01

11

Morbidity and Mortality Weekly Report, December 5, 2003, Volume 52, Number 28. Invasive Streptococcus Pyogenes After Allograft Implantation, Colorado, 2003.  

National Technical Information Service (NTIS)

The report describes a case of invasive disease with streptococcus pyogens (i.e., group A streptococcus (GAS)), after reconstructive knee surgery using contaminated allograft tissue and provides recommendations to reduce the risk for allograft-associated ...

2003-01-01

12

Gene Repertoire Evolution of Streptococcus pyogenes Inferred from Phylogenomic Analysis with Streptococcus canis and Streptococcus dysgalactiae  

PubMed Central

Streptococcus pyogenes, is an important human pathogen classified within the pyogenic group of streptococci, exclusively adapted to the human host. Our goal was to employ a comparative evolutionary approach to better understand the genomic events concomitant with S. pyogenes human adaptation. As part of ascertaining these events, we sequenced the genome of one of the potential sister species, the agricultural pathogen S. canis, and combined it in a comparative genomics reconciliation analysis with two other closely related species, Streptococcus dysgalactiae and Streptococcus equi, to determine the genes that were gained and lost during S. pyogenes evolution. Genome wide phylogenetic analyses involving 15 Streptococcus species provided convincing support for a clade of S. equi, S. pyogenes, S. dysgalactiae, and S. canis and suggested that the most likely S. pyogenes sister species was S. dysgalactiae. The reconciliation analysis identified 113 genes that were gained on the lineage leading to S. pyogenes. Almost half (46%) of these gained genes were phage associated and 14 showed significant matches to experimentally verified bacteria virulence factors. Subsequent to the origin of S. pyogenes, over half of the phage associated genes were involved in 90 different LGT events, mostly involving different strains of S. pyogenes, but with a high proportion involving the horse specific pathogen S. equi subsp. equi, with the directionality almost exclusively (86%) in the S. pyogenes to S. equi direction. Streptococcus agalactiae appears to have played an important role in the evolution of S. pyogenes with a high proportion of LGTs originating from this species. Overall the analysis suggests that S. pyogenes adaptation to the human host was achieved in part by (i) the integration of new virulence factors (e.g. speB, and the sal locus) and (ii) the construction of new regulation networks (e.g. rgg, and to some extent speB).

Lefebure, Tristan; Richards, Vince P.; Lang, Ping; Pavinski-Bitar, Paulina; Stanhope, Michael J.

2012-01-01

13

[Streptococcus pyogenes--much more than the aetiological agent of scarlet fever].  

PubMed

The grampositive bacterium S. pyogenes (beta-haemolytic group A Streptococcus) is a natural colonizer of the human oropharynx mucous membrane and one of the most common agents of infectious diseases in humans. S. pyogenes causes the widest range of disease in humans among all bacterial pathogens. It is responsible for various skin infections such as impetigo contagiosa and erysipelas, and localized mucous membrane infections of the oropharynx (e. g. tonsillitis and pharyngitis). Betahaemolytic group A Streptococcus causes also invasive diseases such as sepses including puerperal sepsis. Additionally, S. pyogenes induces toxin-mediated syndromes, i. e. scarlet fever, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF). STSS and NF are severe, frequently fatal diseases that have emerged in Europe and Northern America during the last two decades. Finally, some immunpathological diseases such as acute rheumatic fever and glomerulonephritis also result from S. pyogenes infections. Most scientists recommend penicillins (benzylpenicillin, phenoxymethylpenicllin) as drugs of first choice for treatment of Streptococcus tonsillopharyngitis and scarlet fever. Erysipelas and some other skin infections should be treated with benzylpenicillin. Intensive care measurements are needed for treatment of severe toxin-mediated S. pyogenes diseases. These measurements include the elimination of internal bacterial foci, concomitant application of clindamycin and benzylpenicillin and suitable treatment of shock symptoms. Management of immunpathological diseases requires antiphlogistical therapy. Because of the wide distribution of S. pyogenes in the general population and the lack of an effective vaccine, possibilities for prevention allowing a suitable protection for diseases due to S. pyogenes are very limited. PMID:19947304

Stock, Ingo

2009-11-01

14

Thermoregulation of Capsule Production by Streptococcus pyogenes  

PubMed Central

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.

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

2012-01-01

15

CRISPR Inhibition of Prophage Acquisition in Streptococcus pyogenes  

Microsoft Academic Search

Streptococcus pyogenes, one of the major human pathogens, is a unique species since it has acquired diverse strain-specific virulence properties mainly through the acquisition of streptococcal prophages. In addition, S. pyogenes possesses clustered regularly interspaced short palindromic repeats (CRISPR)\\/Cas systems that can restrict horizontal gene transfer (HGT) including phage insertion. Therefore, it was of interest to examine the relationship between

Takashi Nozawa; Nayuta Furukawa; Chihiro Aikawa; Takayasu Watanabe; Bijaya Haobam; Ken Kurokawa; Fumito Maruyama; Ichiro Nakagawa

2011-01-01

16

Novel strategies for controlling Streptococcus pyogenes infection and associated diseases: from potential peptide vaccines to antibody immunotherapy  

Microsoft Academic Search

Infections caused by group A streptococcus (GAS) represent a public health problem in both developing and developed countries. The current available methods of prevention are either inadequate or ineffective, which is highlighted by the resurgence in invasive GAS infections over the past two decades. The management of GAS and associated diseases requires new and improved approaches. This review discusses various

Manisha Pandey; Silvana Sekuloski; Michael R Batzloff; Batzloff

2009-01-01

17

Interactions of Lactobacilli with Pathogenic Streptococcus pyogenes  

PubMed Central

Objective. To determine whether (1) a decreased concentration of Lactobacilli allows S. pyogenes to grow; (2) S. pyogenes is able to grow in the presence of healthy Lactobacillus concentrations; (3) S. pyogenes is capable of inhibiting Lactobacilli. Methods. One hundred fifty patient samples of S. pyogenes were mixed with four different concentrations of L. crispatus and L. jensenii. Colony counts and pH measurements were taken from these concentrations and compared using t-tests and ANOVA statistical analyses. Results. Statistical tests showed no significant difference between the colony counts of S. pyogenes by itself and growth when mixed with Lactobacilli, and no significant difference between the colony counts of S. pyogenes in the four different concentrations of Lactobacilli. Conclusion. The statistical data representing the growth of these two organisms suggests that Lactobacilli did not inhibit the growth of S. pyogenes. Also, S. pyogenes did not inhibit the growth of Lactobacilli.

Westbroek, Mark L.; Davis, Crystal L.; Fawson, Lena S.; Price, Travis M.

2010-01-01

18

Characterization of Streptococcus pyogenes ?-NAD+ Glycohydrolase  

PubMed Central

The Gram-positive pathogen Streptococcus pyogenes injects a ?-NAD+ glycohydrolase (SPN) into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. In this compartment, SPN accelerates the death of the host cell by an unknown mechanism that may involve its ?-NAD+-dependent enzyme activities. SPN has been reported to possess the unique characteristic of not only catalyzing hydrolysis of ?-NAD+, but also carrying out ADP-ribosyl cyclase and ADP-ribosyltransferase activities, making SPN the only ?-NAD+ glycohydrolase that can catalyze all of these reactions. With the long term goal of understanding how these activities may contribute to pathogenesis, we have further characterized the enzymatic activity of SPN using highly purified recombinant protein. Kinetic studies of the multiple activities of SPN revealed that SPN possessed only ?-NAD+ hydrolytic activity and lacked detectable ADP-ribosyl cyclase and ADP-ribosyltransferase activities. Similarly, SPN was unable to catalyze cyclic ADPR hydrolysis, and could not catalyze methanolysis or transglycosidation. Kinetic analysis of product inhibition by recombinant SPN demonstrated an ordered uni-bi mechanism, with ADP-ribose being released as a second product. SPN was unaffected by product inhibition using nicotinamide, suggesting that this moiety contributes little to the binding energy of the substrate. Upon transformation, SPN was toxic to Saccharomyces cerevisiae, whereas a glycohydrolase-inactive SPN allowed for viability. Taken together, these data suggest that SPN functions exclusively as a strict ?-NAD+ glycohydrolase during pathogenesis.

Ghosh, Joydeep; Anderson, Patricia J.; Chandrasekaran, Sukantha; Caparon, Michael G.

2010-01-01

19

Vaccine based on a ubiquitous cysteinyl protease and streptococcal pyrogenic exotoxin A protects against Streptococcus pyogenes sepsis and toxic shock  

Microsoft Academic Search

BACKGROUND: The gram-positive bacterium Streptococcus pyogenes is a common pathogen of humans that causes invasive infections, toxic-shock syndrome, rheumatic fever, necrotizing fasciitis and other diseases. Detection of antibiotic resistance in clinical isolates has renewed interest in development of new vaccine approaches for control S. pyogenes sepsis. In the study presented, a novel protein vaccine was examined. The vaccine was based

Robert G Ulrich

2008-01-01

20

Severe Streptococcus pyogenes infections, United Kingdom, 2003-2004.  

PubMed

As part of a Europe-wide initiative to explore current epidemiologic patterns of severe disease caused by Streptococcus pyogenes, the United Kingdom undertook enhanced population-based surveillance during 2003-2004. A total of 3,775 confirmed cases of severe S. pyogenes infection were identified over 2 years, 3.33/100,000 population, substantially more than previously estimated. Skin/soft tissue infections were the most common manifestation (42%), followed by respiratory tract infections (17%). Injection drug use was identified as a risk factor for 20% of case-patients. One in 5 infected case-patients died within 7 days of diagnosis; the highest mortality rate was for cases of necrotizing fasciitis (34%). Nonsteroidal antiinflammatory drugs, alcoholism, young age, and infection with emm/M3 types were independently associated with increased risk for streptococcal toxic shock syndrome. Understanding the pattern of these diseases and predictors of poor patient outcome will help with identification and assessment of the potential effect of targeted interventions. PMID:18258111

Lamagni, Theresa L; Neal, Shona; Keshishian, Catherine; Alhaddad, Neelam; George, Robert; Duckworth, Georgia; Vuopio-Varkila, Jaana; Efstratiou, Androulla

2008-02-01

21

Parameters Affecting the Adherence and Tissue Tropisms of Streptococcus pyogenes  

PubMed Central

Virulent M protein-containing strains of Streptococcus pyogenes were found to adhere well to human pharyngeal cells in vitro. In contrast, an avirulent M - strain and an enteropathogenic Escherichia coli strain adhered feebly. When various rat tissues were exposed to mixtures of a virulent S. pyogenes strain and an enteropathogenic E. coli strain, the relative proportions of the two pathogenic strains recovered from mucosal surfaces differed among the sites studied. S. pyogenes cells were found to adhere in higher proportions than enteropathogenic E. coli cells to the mucosal surfaces of rat tongues, whereas on surfaces of the urinary bladder, their affinities were reversed. The data indicate that bacterial adherence is influenced by the specificity of both the bacterial and epithelial surfaces, and they suggest that adherence may influence the tissue tropisms of pathogens. Early stationary-phase cells of S. pyogenes attached better to epithelial cells than did bacteria in other growth phases. The adherence of S. pyogenes cells was impaired by pretreatment with trypsin, wheat germ lipase, Tween 80, Triton X-100, sodium lauryl sulfate, heat at 56 C, anti-group A antiserum, the presence of phospholipids, and preincubation of the epithelial cells with Streptococcus salivarius cell walls. Altering the pH or treatment with ethylenediaminetetraacetic acid had no effect on the ability of S. pyogenes cells to adhere.

Ellen, Richard P.; Gibbons, Ronald J.

1974-01-01

22

Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole?  

PubMed

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

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

2012-10-10

23

Is Streptococcus pyogenes Resistant or Susceptible to Trimethoprim-Sulfamethoxazole?  

PubMed Central

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.

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

2012-01-01

24

Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model  

PubMed Central

Background Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection. Methodology/Principal Findings A broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto -treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-? and a decreased level of TNF-? in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-? and decreased mRNA level of TNF-? compared with control macrophage. Conclusions/Significance Hainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically.

Minami, Masaaki; Ichikawa, Mariko; Hata, Nanako; Hasegawa, Tadao

2011-01-01

25

In Vitro Development of Resistance to Six Quinolones in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus  

PubMed Central

Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus isolates were exposed to subinhibitory MICs of ciprofloxacin, sparfloxacin, gatifloxacin, moxifloxacin, clinafloxacin, and gemifloxacin during a 10-day period. Subculturing led to resistance development, regardless of the initial potencies of the quinolones. None of the quinolones was associated with a significantly slower rate of resistance development.

Boos, Mechthild; Mayer, Susanne; Fischer, Ansgar; Kohrer, Karl; Scheuring, Sibylle; Heisig, Peter; Verhoef, Jan; Fluit, Ad C.; Schmitz, F.-J.

2001-01-01

26

Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation.  

PubMed

Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year. GAS infections require the capacity of the pathogen to adhere to host tissues and assemble in cell aggregates. Furthermore, a role for biofilms in GAS pathogenesis has recently been proposed. Here we investigated the role of GAS pili in biofilm formation. We demonstrated that GAS pilus-negative mutants, in which the genes encoding either the pilus backbone structural protein or the sortase C1 have been deleted, showed an impaired capacity to attach to a pharyngeal cell line. The same mutants were much less efficient in forming cellular aggregates in liquid culture and microcolonies on human cells. Furthermore, mutant strains were incapable of producing the typical three-dimensional layer with bacterial microcolonies embedded in a carbohydrate polymeric matrix. Complemented mutants had an adhesion and aggregation phenotype similar to the wild-type strain. Finally, in vivo expression of pili was indirectly confirmed by demonstrating that most of the sera from human patients affected by GAS-mediated pharyngitis recognized recombinant pili proteins. These data support the role of pili in GAS adherence and colonization and suggest a general role of pili in all pathogenic streptococci. PMID:17501921

Manetti, Andrea G O; Zingaretti, Chiara; Falugi, Fabiana; Capo, Sabrina; Bombaci, Mauro; Bagnoli, Fabio; Gambellini, Gabriella; Bensi, Giuliano; Mora, Marirosa; Edwards, Andrew M; Musser, James M; Graviss, Edward A; Telford, John L; Grandi, Guido; Margarit, Immaculada

2007-05-01

27

Bacteremic pneumococcal cellulitis compared with bacteremic cellulitis caused by Staphylococcus aureus and Streptococcus pyogenes.  

PubMed

In order to better characterize bacteremic cellulitis caused by Streptococcus pneumoniae, a review was conducted of 10 cases of bacteremic pneumococcal cellulitis, which represented 0.9% of all cases of pneumococcal bacteremia (n=1,076) and 3.2% of all cases of community-acquired bacteremic cellulitis (n=312) that occurred in the Hospital de Bellvitge, Barcelona, from 1984 to 2001. In addition to these 10 cases, 28 cases of bacteremic pneumococcal cellulitis from the literature (Medline 1975-2001) were reviewed. Pneumococcal cellulitis of the face, neck, and trunk was observed more frequently in patients with systemic lupus erythematosus and hematologic disorders, while pneumococcal cellulitis of the limbs was more common in patients with diabetes, alcoholism, and parenteral drug use. In the Hospital de Bellvitge group, bacteremic cellulitis due to Streptococcus pneumoniae was more frequently associated with severe underlying diseases than that due to Staphylococcus aureus or Streptococcus pyogenes (100%, 57%, and 72%, respectively;P=0.01). A concomitant extracutaneous focus of infection (e.g., respiratory tract infection) suggesting hematogenous spread with metastatic cellulitis was more frequent in patients with pneumococcal cellulitis, while a local cutaneous entry of microorganisms was feasible in most patients with Staphylococcus aureus or Streptococcus pyogenes cellulitis. The 30-day mortality was 10% in patients with pneumococcal cellulitis, 13% in patients with Staphylococcus aureus cellulitis, and 23% in patients with Streptococcus pyogenes cellulitis (P=0.3). Thus, bacteremic pneumococcal cellulitis is an unusual manifestation of pneumococcal disease and occurs mainly in patients with severe underlying diseases. In most cases, pneumococcal cellulitis has a different pathophysiologic mechanism than cellulitis caused by Staphylococcus aureus or Streptococcus pyogenes. PMID:12783279

Capdevila, O; Grau, I; Vadillo, M; Cisnal, M; Pallares, R

2003-06-03

28

In Vitro Antibacterial Activity of Essential Oils against Streptococcus pyogenes  

PubMed Central

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.

Sfeir, Julien; Lefrancois, Corinne; Baudoux, Dominique; Derbre, Severine; Licznar, Patricia

2013-01-01

29

In Vitro Antibacterial Activity of Essential Oils against Streptococcus pyogenes.  

PubMed

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

Sfeir, Julien; Lefrançois, Corinne; Baudoux, Dominique; Derbré, Séverine; Licznar, Patricia

2013-04-11

30

Regulation of virulence gene expression in Streptococcus pyogenes  

PubMed Central

Differential mRNA stability is an important mechanism for regulation of virulence factors in Streptococcus pyogenes (group A streptococcus, GAS), a serious and prevalent human pathogen. We have described 2 Classes of mRNA in GAS that are distinguishable by (1) stability in the stationary phase of growth, (2) kinetics of decay in exponential phase and (3) effect of depletion of RNases J1 and J2 and polynucleotide phosphorylase (PNPase) on decay in exponential phase. We discuss features of the structure of an mRNA that appear to be important for determining the Class to which it belongs and present a model to explain differential mRNA decay.

Bugrysheva, Julia V

2010-01-01

31

EndoS and SpeB from Streptococcus pyogenes Inhibit Immunoglobulin-Mediated Opsonophagocytosis  

PubMed Central

The human pathogen Streptococcus pyogenes primarily infects the upper respiratory tract and skin, but occasionally it disseminates and causes severe invasive disease with high mortality. This study revealed that the activity of extracellular EndoS, which hydrolyzes the functionally important N-linked oligosaccharides on opsonizing immunoglobulin G (IgG), contributes to increased survival of S. pyogenes in human blood ex vivo. The inability to kill the bacteria is due to reduced binding of IgG to Fc receptors and impaired classical pathway-mediated activation of complement. In addition, the activity of extracellular SpeB, which cleaves IgG into Fc and Fab fragments, also increases bacterial survival. This suggests that S. pyogenes expresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system.

Collin, Mattias; Svensson, Mikael D.; Sjoholm, Anders G.; Jensenius, Jens C.; Sjobring, Ulf; Olsen, Arne

2002-01-01

32

EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis.  

PubMed

The human pathogen Streptococcus pyogenes primarily infects the upper respiratory tract and skin, but occasionally it disseminates and causes severe invasive disease with high mortality. This study revealed that the activity of extracellular EndoS, which hydrolyzes the functionally important N-linked oligosaccharides on opsonizing immunoglobulin G (IgG), contributes to increased survival of S. pyogenes in human blood ex vivo. The inability to kill the bacteria is due to reduced binding of IgG to Fc receptors and impaired classical pathway-mediated activation of complement. In addition, the activity of extracellular SpeB, which cleaves IgG into Fc and Fab fragments, also increases bacterial survival. This suggests that S. pyogenes expresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system. PMID:12438337

Collin, Mattias; Svensson, Mikael D; Sjöholm, Anders G; Jensenius, Jens C; Sjöbring, Ulf; Olsén, Arne

2002-12-01

33

Prognostic Value and Therapeutic Potential of TREM-1 in Streptococcus pyogenes- Induced Sepsis.  

PubMed

TREM-1 (triggering receptor expressed on myeloid cells) is a surface molecule expressed on neutrophils and macrophages which has been implicated in the amplification of inflammatory responses triggered during infection. In the present study, we have investigated the clinical significance of TREM-1 in Streptococcus pyogenes-induced severe sepsis in both experimentally infected mice as well as in patients with streptococcal toxic shock. We found that S. pyogenes induced a dose-dependent upregulation of TREM-1 in in vitro cultured phagocytic cells and in the organs of S. pyogenes-infected mice. Furthermore, we reported a positive correlation between serum levels of soluble TREM-1 (sTREM-1) and disease severity in infected patients as well as in experimentally infected mice. Hence, sTREM-1 may represent a useful surrogate marker for streptococcal sepsis. We found that modulation of TREM-1 by administration of the TREM-1 decoy receptor rTREM-1/Fc substantially attenuated the synthesis of inflammatory cytokines. More importantly, treatment of S. pyogenes-infected septic mice with rTREM-1/Fc or the synthetically produced conserved extracellular domain LP17 significantly improved disease outcome. In summary, our data suggest that TREM-1 may not only represent a valuable marker for S. pyogenes infection severity but it may also be an attractive target for the treatment of streptococcal sepsis. PMID:23571837

Horst, Sarah A; Linnér, Anna; Beineke, Andreas; Lehne, Sabine; Höltje, Claudia; Hecht, Alexander; Norrby-Teglund, Anna; Medina, Eva; Goldmann, Oliver

2013-04-04

34

Inhibition of Streptococcus pyogenes Biofilm Formation by Coral-Associated Actinomycetes  

Microsoft Academic Search

Streptococcus pyogenes biofilms tend to exhibit significant tolerance to antimicrobials during infections. We screened coral-associated actinomycetes\\u000a (CAA) for antibiofilm activity against different biofilm forming M serotype of Streptococcus pyogenes. Actinomycetes isolated from the mucus of the coral Acropora digitifera were screened for antibiofilm activity against S. pyogenes biofilms wherein several isolates clearly demonstrated antibiofilm activity. The biofilm inhibitory concentrations (BICs)

Paramasivam Nithyanand; Ramalingam Thenmozhi; Janarthanam Rathna; Shunmugiah Karutha Pandian

2010-01-01

35

Low antibody levels against cell wall-attached proteins of Streptococcus pyogenes predispose for severe invasive disease.  

PubMed

Acute-phase serum samples from 70 patients with group A streptococcal (GAS) invasive disease were analyzed for IgG antibodies against 6 recently characterized GAS virulence factors (SclA, SclB, GRAB, MtsA, EndoS, and IdeS) and SpeB. Antibody levels against the cell wall-attached GAS antigens SclA, SclB, and GRAB were significantly lower in patients with severe invasive disease (streptococcal toxic shock syndrome [STSS] and/or necrotizing fasciitis [NF]; n=35), compared with levels in patients with nonsevere GAS bacteremia (n=35). Among patients with severe invasive disease, significantly lower antibody levels against GRAB were found in patients with STSS (n=10) than in patients with NF (n=17). Antibody levels against SpeB in patients with severe bacteremia were similar to those in patients with nonsevere bacteremia, and levels in patients with STSS were similar to those in patients with NF. The data indicate that immunity to cell wall-attached proteins may play a role in the protection against severe invasive disease and that antibodies against GRAB may be of importance in the pathogenesis of STSS. PMID:14976595

Akesson, Per; Rasmussen, Magnus; Mascini, Ellen; von Pawel-Rammingen, Ulrich; Janulczyk, Robert; Collin, Mattias; Olsen, Arne; Mattsson, Eva; Olsson, Martin L; Bjorck, Lars; Christensson, Bertil

2004-02-18

36

Cationic Antimicrobial Peptides Disrupt the Streptococcus pyogenes ExPortal  

PubMed Central

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.

Vega, Luis Alberto; Caparon, Michael G.

2012-01-01

37

Extensive Diversity of Streptococcus pyogenes in a Remote Human Population Reflects Global-Scale Transmission Rather than Localised Diversification  

PubMed Central

The Indigenous population of the Northern Territory of Australia (NT) suffers from a very high burden of Streptococcus pyogenes disease, including cardiac and renal sequelae. The aim of this study was to determine if S. pyogenes isolated from this population represent NT endemic strains, or conversely reflect strains with global distribution. emm sequence typing data were used to select 460 S. pyogenes isolates representing NT S. pyogenes diversity from 1987–2008. These isolates were genotyped using either multilocus sequence typing (MLST) or a high resolution melting-based MLST surrogate (Minim typing). These data were combined with MLST data from other studies on NT S. pyogenes to yield a set of 731 MLST or Minim typed isolates for analysis. goeBURST analysis of MLST allelic profiles and neighbour-joining trees of the MLST allele sequences revealed that a large proportion of the known global S. pyogenes MLST-defined diversity has now been found in the NT. Specifically, fully sequence typed NT isolates encompass 19% of known S. pyogenes STs and 43% of known S. pyogenes MLST alleles. These analyses provided no evidence for major NT-endemic strains, with many STs and MLST alleles shared between the NT and the rest of the world. The relationship between the number of known Minim types, and the probability that a Minim type identified in a calendar year would be novel was determined. This revealed that Minim types typically persist in the NT for >1 year, and indicate that the majority of NT Minim types have been identified. This study revealed that many diverse S. pyogenes strains exhibit global scale mobility that extends to isolated populations. The burden of S. pyogenes disease in the NT is unlikely to be due to the nature of NT S. pyogenes strains, but is rather a function of social and living conditions.

Towers, Rebecca J.; Carapetis, Jonathan R.; Currie, Bart J.; Davies, Mark R.; Walker, Mark J.; Dougan, Gordon; Giffard, Philip M.

2013-01-01

38

Extensive Diversity of Streptococcus pyogenes in a Remote Human Population Reflects Global-Scale Transmission Rather than Localised Diversification.  

PubMed

The Indigenous population of the Northern Territory of Australia (NT) suffers from a very high burden of Streptococcus pyogenes disease, including cardiac and renal sequelae. The aim of this study was to determine if S. pyogenes isolated from this population represent NT endemic strains, or conversely reflect strains with global distribution. emm sequence typing data were used to select 460 S. pyogenes isolates representing NT S. pyogenes diversity from 1987-2008. These isolates were genotyped using either multilocus sequence typing (MLST) or a high resolution melting-based MLST surrogate (Minim typing). These data were combined with MLST data from other studies on NT S. pyogenes to yield a set of 731 MLST or Minim typed isolates for analysis. goeBURST analysis of MLST allelic profiles and neighbour-joining trees of the MLST allele sequences revealed that a large proportion of the known global S. pyogenes MLST-defined diversity has now been found in the NT. Specifically, fully sequence typed NT isolates encompass 19% of known S. pyogenes STs and 43% of known S. pyogenes MLST alleles. These analyses provided no evidence for major NT-endemic strains, with many STs and MLST alleles shared between the NT and the rest of the world. The relationship between the number of known Minim types, and the probability that a Minim type identified in a calendar year would be novel was determined. This revealed that Minim types typically persist in the NT for >1 year, and indicate that the majority of NT Minim types have been identified. This study revealed that many diverse S. pyogenes strains exhibit global scale mobility that extends to isolated populations. The burden of S. pyogenes disease in the NT is unlikely to be due to the nature of NT S. pyogenes strains, but is rather a function of social and living conditions. PMID:24066079

Towers, Rebecca J; Carapetis, Jonathan R; Currie, Bart J; Davies, Mark R; Walker, Mark J; Dougan, Gordon; Giffard, Philip M

2013-09-16

39

Kinetic characterization of arginine deiminase and carbamate kinase from Streptococcus pyogenes M49.  

PubMed

Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen causing mild superficial infections of skin and mucous membranes, but also life-threatening systemic diseases. S. pyogenes and other prokaryotic organisms use the arginine deiminase system (ADS) for survival in acidic environments. In this study, the arginine deiminase (AD), and carbamate kinase (CK) from S. pyogenes M49 strain 591 were heterologously expressed in Escherichia coli DH5?, purified, and kinetically characterized. AD and CK from S. pyogenes M49 share high amino acid sequence similarity with the respective enzymes from Lactococcus lactis subsp. lactis IL1403 (45.6% and 53.5% identical amino acids) and Enterococcus faecalis V583 (66.8% and 66.8% identical amino acids). We found that the arginine deiminase of S. pyogenes is not allosterically regulated by the intermediates and products of the arginine degradation (e.g., ATP, citrulline, carbamoyl phosphate). The Km and Vmax values for arginine were 1.13±0.12mM (mean±SD) and 1.51±0.07?mol/min/mg protein. The carbamate kinase is inhibited by ATP but unaffected by arginine and citrulline. The Km and Vmax values for ADP were 0.72±0.08mM and 1.10±0.10?mol/min/mg protein and the Km for carbamoyl phosphate was 0.65±0.07mM. The optimum pH and temperature for both enzymes were 6.5 and 37°C, respectively. PMID:23867361

Hering, Silvio; Sieg, Antje; Kreikemeyer, Bernd; Fiedler, Tomas

2013-07-16

40

Upper limb compartment syndrome secondary to streptococcus pyogenes (Group A streptococcus) infection  

PubMed Central

Compartment syndrome caused by Streptococcus pyogenes (Group A streptococcus) has rarely been described. We report a case of a healthy 44-year-old male who presented with compartment syndrome of the right forearm and subsequent acute respiratory distress syndrome. The patient received antibiotics and urgent surgical decompression, followed by delayed wound closure without the need for skin grafting. The patient recovered with no loss of power, sensation or range of movement. High index of suspicion, early intervention and excellent post-operative management were essential in recovery.

Taylor, J; Wojcik, A

2011-01-01

41

Antibodies against a Surface Protein of Streptococcus pyogenes Promote a Pathological Inflammatory Response  

PubMed Central

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein–induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein–fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.

Kahn, Fredrik; Morgelin, Matthias; Shannon, Oonagh; Norrby-Teglund, Anna; Herwald, Heiko; Olin, Anders I.; Bjorck, Lars

2008-01-01

42

Decreased activity of erythromycin against Streptococcus pyogenes in Taiwan.  

PubMed Central

A total of 78 clinical isolates of Streptococcus pyogenes were collected from January 1992 through December 1993 from patients in southern Taiwan. The in vitro activities of 10 antimicrobial agents were determined by the agar dilution method. Penicillin, cephalothin, cefotaxime, vancomycin, and ofloxacin were shown to be active against S. pyogenes isolates, with MICs at which 90% of isolates are inhibited (MIC90s) being < or = 0.03, < or = 0.13, < or = 0.13, < or = 0.13, and < or = 0.25 microgram/ml, respectively. Erythromycin and azithromycin both had poor activities (MIC50s, 16 and >128 micrograms/ml, respectively; MIC90s, >128 and >128 micrograms/ml, respectively). The activities of tetracycline, clindamycin, and chloramphenicol against a significant number of these isolates were also limited. As the MICs of clindamycin and chloramphenicol for the isolates increased, the MICs of the two macrolides also increased. Clindamycin, chloramphenicol, and the two macrolides were less potent against isolates recovered form throat swab samples than against those from blood or other sources. Isolates of the T12 and T1 serotypes accounted for 53.8% of all isolates. The majority (87.5%) of the isolates recovered from throat swab samples were of the T12 serotype, whereas 19.2% of the isolates recovered from blood were of the T12 serotype. In contrast, 66.7% of the isolates of the T1 serotype were derived from blood but none were derived from throat swab samples. Of the 33 T12 serotype isolates, erythromycin MICs for 78.8% of the isolates were >128 micrograms/ml. Because of the poor activities of erythromycin and azithromycin against S. pyogenes isolates from patients in southern Taiwan, these drugs should no longer be considered the drugs of choice for the management of group A streptococcal infections among patients who live in this area.

Hsueh, P R; Chen, H M; Huang, A H; Wu, J J

1995-01-01

43

Typing of Streptococcus pyogenes strains using the phage profiling method  

PubMed Central

We recently developed a method that allows fast differentiation between Streptococcus pyogenes (GAS) strains. The method named phage profiling (PP) is based on a simple assumption that a regular PCR reaction with Taq polymerase and relatively short elongation time is not able to yield long DNA fragment, such as ~40–50 kb integrated prophage. Only fragments without any integrated DNA or short fragments inserted between integration sites can be efficiently amplified. We designed primers that anneal upstream and downstream prophage integration sites, so in simple PCR reaction we can test if any additional DNA is integrated into particular site. Profiling of integrated elements can be used as rapid, high resolution typing method, with the resolution as high as PFGE and is excellent predictor of PFGE type.

Borek, Anna L.; Obszanska, Katarzyna; Hryniewicz, Waleria; Sitkiewicz, Izabela

2012-01-01

44

Detection of Streptococcus pyogenes virulence factors by multiplex PCR  

PubMed Central

Streptococcus pyogenes (GAS) is a human pathogen that causes multiple infections worldwide. The pathogenic properties of GAS strains are often linked to the production of virulence factors such as toxins, proteases or DNases. Detection of virulence factors produced by GAS strains can be used to either determine pathogenic potential of the strain or as a rapid screening and typing method. We recently developed a method to detect simultaneously 20 GAS virulence factors (spd3, sdc, sdaB, sdaD, speB, spyCEP, scpA, mac, sic, speL, K, M, C, I, A, H, G, J, smeZ and ssa) in four low volume multiplex PCR reactions (Borek et al., 2011) and below we present a detailed protocol describing the method.

Borek, Anna L.; Obszanska, Katarzyna; Hryniewicz, Waleria; Sitkiewicz, Izabela

2012-01-01

45

Macrolide-Resistant Streptococcus pyogenes in Norway: Population Structure and Resistance Determinants  

PubMed Central

A 2.7% prevalence of macrolide resistance in 1,657 Norwegian clinical Streptococcus pyogenes isolates was primarily due to erm(TR) (59%) and mef(A) (20%). Four clonal complexes comprised 75% of the strains. Macrolide resistance in S. pyogenes in Norway is imported as resistant strains or locally selected in internationally disseminated susceptible clones.

Littauer, P.; Caugant, D. A.; Sangvik, M.; H?iby, E. A.; Sundsfjord, A.; Simonsen, G. S.

2006-01-01

46

Influenza A Virus-Infected Hosts Boost an Invasive Type of Streptococcus pyogenes Infection in Mice  

Microsoft Academic Search

The apparent worldwide resurgence of invasive Streptococcus pyogenes infection in the last two decades remains unexplained. At present, animal models in which toxic shock-like syndrome or necrotizing fasciitis is induced after S. pyogenes infection are not well developed. We demonstrate here that infection with a nonlethal dose of influenza A virus 2 days before intranasal infection with a nonlethal dose

Shigefumi Okamoto; Shigetada Kawabata; Ichiro Nakagawa; Yoshinobu Okuno; Toshiyuki Goto; Kouichi Sano; Shigeyuki Hamada

2003-01-01

47

Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections  

Microsoft Academic Search

Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we

Michael S. Chaussee; Heather R. Sandbulte; Margaret J. Schuneman; Frank P. DePaula; Leslie A. Addengast; Evelyn H. Schlenker; Victor C. Huber

2011-01-01

48

Inducible cyclooxygenase released prostaglandin E2 modulates the severity of infection caused by Streptococcus pyogenes.  

PubMed

Streptococcus pyogenes is a significant human pathogen that can cause life-threatening invasive infections. Understanding the mechanism of disease is crucial to the development of more effective therapies. In this report, we explored the role of PGE(2), an arachidonic acid metabolite, and its rate-limiting enzyme cyclooxygenase 2 (COX-2) in the pathogenesis of severe S. pyogenes infections. We found that the COX-2 expression levels in tissue biopsies from S. pyogenes-infected patients, as well as in tissue of experimentally infected mice, strongly correlated with the severity of infection. This harmful effect was attributed to PGE(2)-mediated suppression of the bactericidial activity of macrophages through interaction with the G2-coupled E prostanoid receptor. The suppressive effect of PGE(2) was associated with enhanced intracellular cAMP production and was mimicked by the cAMP-elevating agent, forskolin. Activation of protein kinase A (PKA) was the downstream effector mechanisms of cAMP because treatment with PKI(14-22), a highly specific inhibitor of PKA, prevented the PGE(2)-mediated inhibition of S. pyogenes killing in macrophages. The inhibitory effect exerted by PKA in the generation of antimicrobial oxygen radical species seems to be the ultimate effector mechanism responsible for the PGE(2)-mediated downregulation of the macrophage bactericidal activity. Importantly, either genetic ablation of COX-2, pharmacological inhibition of COX-2 or treatment with the G2-coupled E prostanoid antagonist, AH6809, significantly improved the disease outcome in S. pyogenes infected mice. Therefore, the results of this study open up new perspectives on potential molecular pathways that are prone to pharmacological manipulation during severe streptococcal infections. PMID:20644176

Goldmann, Oliver; Hertzén, Erika; Hecht, Alexander; Schmidt, Heike; Lehne, Sabine; Norrby-Teglund, Anna; Medina, Eva

2010-07-19

49

Nonhemolytic Streptococcus pyogenes Isolates That Lack Large Regions of the sag Operon Mediating Streptolysin S Production?  

PubMed Central

Among nonhemolytic Streptococcus pyogenes (group A streptococcus) strains (n = 9) isolated from patients with pharyngitis or acute otitis media, we identified three deletions in the region from the epf gene, encoding the extracellular matrix binding protein, to the sag operon, mediating streptolysin S production.

Yoshino, Miho; Murayama, Somay Y.; Sunaoshi, Katsuhiko; Wajima, Takeaki; Takahashi, Miki; Masaki, Junko; Kurokawa, Iku; Ubukata, Kimiko

2010-01-01

50

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

PubMed Central

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.

Wong, Samson SY; Yuen, Kwok-Yung

2012-01-01

51

Population Biology of the Human Restricted Pathogen, Streptococcus pyogenes  

PubMed Central

S. pyogenes, also referred to as ?-hemolytic group A streptococci, are strictly human pathogens with a global distribution and high prevalence of infection. The organisms are characterized by high levels of genetic recombination, extensive strain diversity, and a narrow habitat. This review highlights many key features of the population genetics and molecular epidemiology of this biologically diverse bacterial species, with special emphasis on ecological subdivisions and tissue-specific infections, strain diversity and population dynamics in communities, selection pressures arising from the specific host immune response and antibiotic exposure, and within-host selection during the course of invasive disease.

Bessen, Debra E.

2009-01-01

52

Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors.  

PubMed

Streptococcus pyogenes is an important human pathogen that causes invasive diseases such as necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome. We investigated the function of a major cysteine protease from S. pyogenes that affects the amount of C1-esterase inhibitor (C1-INH) and other complement factors and aimed to elucidate the mechanism involved in occurrence of streptococcal toxic shock syndrome from the aspect of the complement system. First, we revealed that culture supernatant of a given S. pyogenes strain and recombinant SpeB degraded the C1-INH. Then, we determined the N-terminal sequence of the C1-INH fragment degraded by recombinant SpeB. Interestingly, the region containing one of the identified cleavage sites is not present in patients with C1-INH deficiency. Scanning electron microscopy of the speB mutant incubated in human serum showed the abnormal superficial architecture and irregular oval structure. Furthermore, unlike the wild-type strain, that mutant strain showed lower survival capacity than normal as compared with heat-inactivated serum, whereas it had a significantly higher survival rate in serum without the C1-INH than in normal serum. Also, SpeB degraded multiple complement factors and the membrane attack complex. Flow cytometric analyses revealed deposition of C9, one of the components of membrane the attack complex, in greater amounts on the surface of the speB mutant, whereas lower amounts of C9 were bound to the wild-type strain surface. These results suggest that SpeB can interrupt the human complement system via degrading the C1-INH, thus enabling S. pyogenes to evade eradication in a hostile environment. PMID:23589297

Honda-Ogawa, Mariko; Ogawa, Taiji; Terao, Yutaka; Sumitomo, Tomoko; Nakata, Masanobu; Ikebe, Kazunori; Maeda, Yoshinobu; Kawabata, Shigetada

2013-04-15

53

Typing of Streptococcus pyogenes Strains Isolated from Throat Infections in the Region of Aachen, Germany  

Microsoft Academic Search

Background: Changes in the epidemiology of Streptococcus pyogenes infections may be associated with the introduction and reappearance of individual serotypes within a population.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and Methods: Typing of 216 consecutive isolates of S. pyogenes from patients with pharyngitis in the region of Aachen, Germany, was performed by sequencing the emm gene, slide-agglutination of the T-antigen and determining the serum opacity

C. M. Brandt; B. Spellerberg; M. Honscha; N. D. Truong; B. Hoevener; R. Lütticken

2001-01-01

54

Identification of Rgg Binding Sites in the Streptococcus pyogenes Chromosome ? †  

PubMed Central

Streptococcus pyogenes Rgg is a regulatory protein that controls the transcription of 588 genes in strain NZ131 during the post-exponential phase of growth, including the virulence-associated genes encoding the extracellular SpeB protease, pullulanase A (PulA), and two extracellular nucleases (SdaB and Spd-3). Rgg binds to DNA proximally to the speB promoter (PspeB) to activate transcription; however, it is not known if Rgg binds to the promoters of other genes to influence expression, or if the perturbation of other global regulons accounts for the genome-wide changes in expression associated with the mutant. To address this issue, chromatin immunoprecipitation followed by DNA microarray analysis (ChIP-chip) was used to identify the DNA binding sites of Rgg. Rgg bound to 65 sites in the chromosome. Thirty-five were within noncoding DNA, and 43% of these were adjacent to genes previously identified as regulated by Rgg. Electrophoretic mobility shift assays were used to assess the binding of Rgg to a subset of sites bound in vivo, including the noncoding DNA upstream of speB, the genes encoding PulA, Spd-3, and a transcriptional regulator (SPY49_1113), and prophage-associated genes encoding a putative integrase (SPY49_0746) and a surface antigen (SPY49_0396). Rgg bound to all target DNAs in vitro, consistent with the in vivo results. Finally, analyses with a transcriptional reporter system showed that the DNA bound by Rgg contained an active promoter that was regulated by Rgg. Overall, the results indicate that Rgg binds specifically to multiple sites in the chromosome, including prophage DNA, to influence gene expression.

Anbalagan, Srivishnupriya; McShan, W. Michael; Dunman, Paul M.; Chaussee, Michael S.

2011-01-01

55

Dissemination of emm28 erythromycin-, clindamycin- and bacitracin-resistant Streptococcus pyogenes in Spain.  

PubMed

Reported here is an unusual cluster of non-invasive infections caused by an emm28 Streptococcus pyogenes strain resistant to bacitracin, erythromycin and clindamycin detected in Santander, Spain. Since one of the characteristics of group A streptococci is their almost uniform susceptibility to bacitracin, this finding was unusual, and a search for bacitracin-resistant Streptococcus pyogenes strains was conducted in two other distant cities of Spain (Madrid and San Sebastián) where their presence was confirmed. These strains were frequently associated with erythromycin- and clindamycin-resistance, and most of them belonged to a unique emm28 T28, ST52 clone. PMID:14712367

Perez-Trallero, E; Garcia, C; Orden, B; Marimon, J M; Montes, M

2004-01-08

56

Variation in Streptococcus pyogenes NAD+ glycohydrolase is associated with tissue tropism.  

PubMed

Streptococcus pyogenes is an important pathogen that causes a variety of diseases. The most common infections involve the throat (pharyngitis) or skin (impetigo); however, the factors that determine tissue tropism and severity are incompletely understood. The S. pyogenes NAD(+) glycohydrolase (SPN) is a virulence factor that has been implicated in contributing to the pathogenesis of severe infections. However, the role of SPN in determining the bacterium's tissue tropism has not been evaluated. In this report, we examine the sequences of spn and its endogenous inhibitor ifs from a worldwide collection of S. pyogenes strains. Analysis of average pairwise nucleotide diversity, average number of nucleotide differences, and ratio of nonsynonymous to synonymous substitutions revealed significant diversity in spn and ifs. Application of established models of molecular evolution shows that SPN is evolving under positive selection and diverging into NAD(+) glycohydrolase (NADase)-active and -inactive subtypes. Additionally, the NADase-inactive SPN subtypes maintain the characteristics of a functional gene while ifs becomes a pseudogene. Thus, NADase-inactive SPN continues to evolve under functional constraint. Furthermore, NADase activity did not correlate with invasive disease in our collection but was associated with tissue tropism. The ability to cause infection at both the pharynx and the skin ("generalist" strains) is correlated with NADase-active SPN, while the preference for causing infection at either the throat or the skin ("specialist" strains) is associated with NADase-inactive SPN. These findings suggest that SPN has a NADase-independent function and prompt a reevaluation of the role of SPN in streptococcal pathogenesis. PMID:20494994

Riddle, David J; Bessen, Debra E; Caparon, Michael G

2010-05-21

57

Variation in Streptococcus pyogenes NAD+ Glycohydrolase Is Associated with Tissue Tropism? †  

PubMed Central

Streptococcus pyogenes is an important pathogen that causes a variety of diseases. The most common infections involve the throat (pharyngitis) or skin (impetigo); however, the factors that determine tissue tropism and severity are incompletely understood. The S. pyogenes NAD+ glycohydrolase (SPN) is a virulence factor that has been implicated in contributing to the pathogenesis of severe infections. However, the role of SPN in determining the bacterium's tissue tropism has not been evaluated. In this report, we examine the sequences of spn and its endogenous inhibitor ifs from a worldwide collection of S. pyogenes strains. Analysis of average pairwise nucleotide diversity, average number of nucleotide differences, and ratio of nonsynonymous to synonymous substitutions revealed significant diversity in spn and ifs. Application of established models of molecular evolution shows that SPN is evolving under positive selection and diverging into NAD+ glycohydrolase (NADase)-active and -inactive subtypes. Additionally, the NADase-inactive SPN subtypes maintain the characteristics of a functional gene while ifs becomes a pseudogene. Thus, NADase-inactive SPN continues to evolve under functional constraint. Furthermore, NADase activity did not correlate with invasive disease in our collection but was associated with tissue tropism. The ability to cause infection at both the pharynx and the skin (“generalist” strains) is correlated with NADase-active SPN, while the preference for causing infection at either the throat or the skin (“specialist” strains) is associated with NADase-inactive SPN. These findings suggest that SPN has a NADase-independent function and prompt a reevaluation of the role of SPN in streptococcal pathogenesis.

Riddle, David J.; Bessen, Debra E.; Caparon, Michael G.

2010-01-01

58

RscA, a Member of the MDR1 Family of Transporters, Is Repressed by CovR and Required for Growth of Streptococcus pyogenes under Heat Stress  

Microsoft Academic Search

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

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

2006-01-01

59

Aberrant Inflammatory Response to Streptococcus pyogenes in Mice Lacking Myeloid Differentiation Factor 88  

PubMed Central

Several in vitro studies have emphasized the importance of toll-like receptor/myeloid differentiation factor 88 (MyD88) signaling in the inflammatory response to Streptococcus pyogenes. Since the extent of inflammation has been implicated in the severity of streptococcal diseases, we have examined here the role of toll-like receptor/MyD88 signaling in the pathophysiology of experimental S. pyogenes infection. To this end, we compared the response of MyD88-knockout (MyD88?/?) after subcutaneous inoculation with S. pyogenes with that of C57BL/6 mice. Our results show that MyD88?/? mice harbored significantly more bacteria in the organs and succumbed to infection much earlier than C57BL/6 animals. Absence of MyD88 resulted in diminished production of inflammatory cytokines such as interleukin-12, interferon-?, and tumor necrosis factor-? as well as chemoattractants such as monocyte chemotactic protein-1 (MCP-1) and Keratinocyte-derived chemokine (KC), and hampered recruitment of effector cells involved in bacterial clearance (macrophages and neutrophils) to the infection site. Furthermore, MyD88?/? but not C57BL/6 mice exhibited a massive infiltration of eosinophils in infected organs, which can be explained by an impaired production of the regulatory chemokines, gamma interferon-induced monokine (MIG/CXCL9) and interferon-induced protein 10 (IP-10/CXCL10), which can inhibit transmigration of eosinophils. Our results indicate that MyD88 signaling targets effector cells to the site of streptococcal infection and prevents extravasation of cells that can induce tissue damage. Therefore, MyD88 signaling may be important for shaping the quality of the inflammatory response elicited during infection to ensure optimal effector functions.

Loof, Torsten G.; Goldmann, Oliver; Gessner, Andre; Herwald, Heiko; Medina, Eva

2010-01-01

60

Clinical significance of inhibition kinetics for Streptococcus pyogenes in response to penicillin  

Microsoft Academic Search

Objectives: The antibiotic mode of action against clinical isolates of Streptococcus pyogenes and physiological factors involved in modifying the inhibitory response to the antibiotic were investigated. Methods: We developed high-resolution respirometry for continuous monitoring of bacterial growth and inhibition kinetics. One hundred and ten clinical isolates from 90 paediatric patients were tested, including 48 isolates obtained from 28 patients with

Christoph Steininger; Franz Allerberger; Erich Gnaiger

2002-01-01

61

Suppression of SV40 Tumors after Immunization with Group A Streptococcus pyogenes and Bordetella pertussis1  

Microsoft Academic Search

SUMMARY Tumors produced by a line of SV40-transformed cells in golden Syrian hamsters were suppressed in 60% of animals immunized with a mixed vaccine of Group A Streptococcus pvogenes and Bordetella pertussis. There was a suppression of tumor growth in 50% of animals immuni\\/ed with 5. pvogenes vaccine alone. Polysaccharides were extracted from 5. pyogenes and tumor cells by an

John L. Collins; Carl J. Wust

62

Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes  

Microsoft Academic Search

Bacteria encounter oxidative stress by exposure to reactive oxygen species (ROS) present in the aerobic environment and during immune responses. In Streptococcus pyogenes, Dpr has been identified as a stress protein conferring resistance to hydrogen peroxide and multiple other stresses. The expression of Dpr is under perR (peroxide stress response regulator) control. However, the exact molecular mechanism of PerR regulation

Chih-Cheng Tsou; Chuan Chiang-Ni; Yee-Shin Lin; Woei-Jer Chuang; Ming-T. Lin; Ching-Chuan Liu; Jiunn-Jong Wu

2010-01-01

63

Establishment of a Superficial Skin Infection Model in Mice by Using Staphylococcus aureus and Streptococcus pyogenes  

Microsoft Academic Search

A new animal model for the purpose of studying superficial infections is presented. In this model an infection is established by disruption of the skin barrier by partial removal of the epidermal layer by tape stripping and subsequent application of the pathogens Staphylococcus aureus and Streptococcus pyogenes. The infection and the infection route are purely topical, in contrast to those

Elisabeth Kugelberg; Tobias Norstrom; Thomas K. Petersen; Tore Duvold; Dan I. Andersson; Diarmaid Hughes

2005-01-01

64

Macrolide- and Telithromycin-resistant Streptococcus pyogenes, Belgium, 1999-20031  

PubMed Central

We found a 13% macrolide resistance in 3,866 Streptococcus pyogenes isolated from tonsillopharyngitis patients; 59% macrolide-resistant isolates were distributed in 5 clones, suggesting the importance of both resistance gene transfer and clonal dissemination in the spread of these organisms. We also report one of the largest collections of telithromycin-resistant isolates.

Lammens, Christine; Chapelle, Sabine; Wijdooghe, Monique; Piessens, Jasper; Van Herck, Koen; Goossens, Herman

2005-01-01

65

Evolution of Transcription Regulatory Genes Is Linked to Niche Specialization in the Bacterial Pathogen Streptococcus pyogenes  

Microsoft Academic Search

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the

Debra E. Bessen; Anand Manoharan; Feng Luo; John E. Wertz; D. Ashley Robinson

2005-01-01

66

Cysteine proteinase SpeB from Streptococcus pyogenes - a potent modifier of immunologically important host and bacterial proteins.  

PubMed

Group A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates that S. pyogenes possess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein from S. pyogenes. Because of its relatively indiscriminant specificity, this enzyme has been shown to degrade the extracellular matrix, cytokines, chemokines, complement components, immunoglobulins, and serum protease inhibitors, to name but a few of the known substrates. Additionally, SpeB regulates other streptococcal proteins by degrading them or releasing them from the bacterial surface. Despite the wealth of literature on putative SpeB functions, there remains much controversy about this enzyme because many of reported activities would produce contradictory physiological results. Here we review all known host and bacterial protein substrates for SpeB, their cleavage sites, and discuss the role of this enzyme in streptococcal pathogenesis based on the current literature. PMID:22050223

Nelson, Daniel C; Garbe, Julia; Collin, Mattias

2011-12-01

67

Fosfomycin Reduces CD15s-Related Antigen Expression of Streptococcus pyogenes  

PubMed Central

We have previously shown the immunological mimicry of human sialyl-Lewisx (CD15s) by a surface antigen of Streptococcus pyogenes. This mimicking surface antigen may act as a ligand to the selectin family and may induce antibody production against CD15s on host cells, suggesting a possible role in the pathogenesis of S. pyogenes. In this study, the effects of antibiotics on the CD15s-related antigen expression of S. pyogenes were examined at a concentration below the MIC (sub-MIC). The amounts of CD15s on the surfaces of S. pyogenes cells and on the surfaces of S. pyogenes biofilms were determined by a whole-cell enzyme-linked immunosorbent assay and by laser scanning fluorescence microscopy, respectively, by using an anti-CD15s monoclonal antibody. At the sub-MICs, fosfomycin (1R,2S-1,2-epoxypropyl phosphonic acid), its enantiomer (1S,2R-1,2-epoxypropyl phosphonic acid), and benzylpenicillin significantly inhibited the CD15s expression of all strains studied. The effects of fosfomycin and its enantiomer on biofilms were also observed by scanning electron microscopy. Incubation of S. pyogenes with the sub-MIC of fosfomycin or its enantiomer, which has no antibacterial activity, reduced the amount of CD15s on the biofilm surface and made it smooth. These results suggest that fosfomycin or its enantiomer might be useful for preventing S. pyogenes adherence to human CD15s receptors and the resulting immunological pathogenicity.

Hirota, Katsuhiko; Murakami, Kinya; Nemoto, Ken; Ono, Tsuneko; Matsuo, Takashi; Kumon, Hiromi; Miyake, Yoichiro

1998-01-01

68

Dynamics of speB mRNA Transcripts in Streptococcus pyogenes  

PubMed Central

Streptococcus pyogenes (group A streptococcus [GAS]) is a human-specific pathogen that causes a variety of diseases ranging from superficial infections to life-threatening diseases. SpeB, a potent extracellular cysteine proteinase, plays an important role in the pathogenesis of GAS infections. Previous studies show that SpeB expression and activity are controlled at the transcriptional and posttranslational levels, though it had been unclear whether speB was also regulated at the posttranscriptional level. In this study, we examined the growth phase-dependent speB mRNA level and decay using quantitative reverse transcription-PCR (qRT-PCR) and Northern blot analyses. We observed that speB mRNA accumulated rapidly during exponential growth, which occurred concomitantly with an increase in speB mRNA stability. A closer observation revealed that the increased speB mRNA stability was mainly due to progressive acidification. Inactivation of RNase Y, a recently identified endoribonuclease, revealed a role in processing and degradation of speB mRNA. We conclude that the increased speB mRNA stability contributes to the rapid accumulation of speB transcript during growth.

Itzek, Andreas; Malke, Horst; Ferretti, Joseph J.

2012-01-01

69

Streptococcus pyogenes degrades extracellular matrix in chondrocytes via MMP-13  

SciTech Connect

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.

Sakurai, Atsuo [Division of Bacteriology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Okahashi, Nobuo [Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871 (Japan); Maruyama, Fumito [Division of Bacteriology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Ooshima, Takashi [Pediatric Dentistry, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871 (Japan); Hamada, Shigeyuki [Advanced Research Institute for the Sciences and Humanities, Nihon University, 6F Ichigaya Tokyu Building, 2-1 Kudan-kita 4-chome, Chiyoda-ku, Tokyo 102-0073 (Japan); Nakagawa, Ichiro [Division of Bacteriology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)], E-mail: ichiro-n@ims.u-tokyo.ac.jp

2008-08-29

70

Lemierre syndrome in a 22-month-old due to Streptococcus pyogenes: a case report.  

PubMed

We report a case of Lemierre syndrome secondary to Streptococcus pyogenes in a 22-month-old girl. This case report and literature review took place at a pediatric intensive care unit at a freestanding tertiary children's hospital. Diagnosis occurred after the discovery of left internal jugular thrombus and multiple metastatic infection sites including the right knee, kidneys, lungs, and brain. Lemierre syndrome can occur in young children secondary to S. pyogenes, and a classic presentation may not occur. A high index of suspicion is crucial to the diagnosis. PMID:22068074

Frizzola, Meg A; Hertzog, James H

2011-11-01

71

Activity of Ceftibuten, Cefaclor, Azithromycin, Clarithromycin, Erythromycin and Telithromycin against Streptococcus pyogenes Clinical Isolates with Different Genotypes and Phenotypes  

Microsoft Academic Search

Background: The growing number of macrolide-resistant strains of Streptococcus pyogenes represents an increasing worldwide problem. Macrolide resistance in S. pyogenes is mediated by several different genes, which determine different levels of resistance to macrolides, lincosamides and streptogramin B (MLS). Methods: This study compared the in vitro antimicrobial activity of azithromycin, clarithromycin, erythromycin, ceftibuten, cefaclor, and telithromycin against 287 strains of

Lorenzo Drago; Sandro Ripa; Claudia Zampaloni; Elena De Vecchi; Luca A. Vitali; Dezemona Petrelli; Manuela Prenna

2005-01-01

72

Effect of subinhibitory concentrations of fluoroquinolones on biofilm production by clinical isolates of Streptococcus pyogenes.  

PubMed

Background & objectives: Subinhibitory concentrations (sub-MICs) of antibiotics, although not able to kill bacteria, but influence bacterial virulence significantly. Fluoroquinolones (FQs) which are used against other bacterial pathogens creates resistance in non-targeted Streptococcus pyogenes. This study was undertaken to characterize the effect of sub-MICs of FQs on S. pyogenes biofilm formation. Methods: Biofilm forming six M serotypes M56, st38, M89, M65, M100 and M74 of S. pyogenes clinical isolates were challenged against four FQs namely, ciprofloxacin, ofloxacin, levofloxacin and norfloxacin. The antibiofilm potential of these FQs was analysed at their subinhibitory concentrations (1/2 to 1/64 MIC) using biofilm assay, XTT reduction assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Results: Among the four FQs tested, ofloxacin and levofloxacin at 1/2 MIC showed the maximum inhibition (92%) of biofilm formation against M56 and M74 serotypes. FQs effectively interfered in the microcolony formation of S. pyogenes isolates at 1/2 to 1/8 sub-MICs. Inhibition of biofilm formation was greatly reduced beyond 1/16 MICs and allowed biofilm formation. XTT reduction assay revealed the increase in metabolic activity of S. pyogenes biofilm against the decrease in FQs concentration. SEM and CLSM validated the potential of sub-MICs of FQs against the six S. pyogenes. Interpretation & conclusions: Our results showed that the inhibitory effect all four FQs on S. pyogenes biofilm formation was concentration dependent. FQs at proper dosage can be effective against S. pyogenes and lower concentrations may allow the bacteria to form barriers against the antibiotic in the form of biofilm. PMID:23760384

Balaji, Kannan; Thenmozhi, Ramalingam; Pandian, Shunmugiah Karutha

2013-05-01

73

A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes.  

PubMed

Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a KD value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases. PMID:23935504

Oehmcke, Sonja; Westman, Johannes; Malmström, Johan; Mörgelin, Matthias; Olin, Anders I; Kreikemeyer, Bernd; Herwald, Heiko

2013-08-01

74

Clinical and Microbiologic Characteristics of Invasive Streptococcus pyogenes Infections in North and South India  

PubMed Central

The lack of epidemiologic data on invasive Streptococcus pyogenes infections in many developing countries is concerning, as S. pyogenes infections are commonly endemic in these areas. Here we present the results of the first prospective surveillance study of invasive Streptococcus pyogenes infections in India. Fifty-four patients with invasive S. pyogenes infections were prospectively enrolled at two study sites, one in the north and one in the south of India. Sterile-site isolates were collected, and clinical information was documented using a standardized questionnaire. Available acute-phase sera were tested for their ability to inhibit superantigens produced by the patient's own isolate using a cell-based neutralizing assay. The most common clinical presentations were bacteremia without focus (30%), pneumonia (28%), and cellulitis (17%). Only two cases of streptococcal toxic shock syndrome and no cases of necrotizing fasciitis were identified. Characterization of the isolates revealed great heterogeneity, with 32 different emm subtypes and 29 different superantigen gene profiles being represented among the 49 sterile-site isolates. Analyses of acute-phase sera showed that only 20% of the cases in the north cohort had superantigen-neutralizing activity in their sera, whereas 50% of the cases from the south site had neutralizing activity. The results demonstrate that there are important differences in both clinical presentation and strain characteristics between invasive S. pyogenes infections in India and invasive S. pyogenes infections in Western countries. The findings underscore the importance of epidemiologic studies on streptococcal infections in India and have direct implications for current vaccine developments.

Haggar, Axana; Nerlich, Andreas; Kumar, Rajesh; Abraham, Vinod J.; Brahmadathan, Kootallur N.; Ray, Pallab; Dhanda, Vanita; Joshua, John Melbin Jose; Mehra, Narinder; Bergmann, Rene; Chhatwal, G. Singh

2012-01-01

75

Clinical and microbiologic characteristics of invasive Streptococcus pyogenes infections in north and south India.  

PubMed

The lack of epidemiologic data on invasive Streptococcus pyogenes infections in many developing countries is concerning, as S. pyogenes infections are commonly endemic in these areas. Here we present the results of the first prospective surveillance study of invasive Streptococcus pyogenes infections in India. Fifty-four patients with invasive S. pyogenes infections were prospectively enrolled at two study sites, one in the north and one in the south of India. Sterile-site isolates were collected, and clinical information was documented using a standardized questionnaire. Available acute-phase sera were tested for their ability to inhibit superantigens produced by the patient's own isolate using a cell-based neutralizing assay. The most common clinical presentations were bacteremia without focus (30%), pneumonia (28%), and cellulitis (17%). Only two cases of streptococcal toxic shock syndrome and no cases of necrotizing fasciitis were identified. Characterization of the isolates revealed great heterogeneity, with 32 different emm subtypes and 29 different superantigen gene profiles being represented among the 49 sterile-site isolates. Analyses of acute-phase sera showed that only 20% of the cases in the north cohort had superantigen-neutralizing activity in their sera, whereas 50% of the cases from the south site had neutralizing activity. The results demonstrate that there are important differences in both clinical presentation and strain characteristics between invasive S. pyogenes infections in India and invasive S. pyogenes infections in Western countries. The findings underscore the importance of epidemiologic studies on streptococcal infections in India and have direct implications for current vaccine developments. PMID:22357508

Haggar, Axana; Nerlich, Andreas; Kumar, Rajesh; Abraham, Vinod J; Brahmadathan, Kootallur N; Ray, Pallab; Dhanda, Vanita; Joshua, John Melbin Jose; Mehra, Narinder; Bergmann, Rene; Chhatwal, G Singh; Norrby-Teglund, Anna

2012-02-22

76

First Streptococcus pyogenes signature-tagged mutagenesis screen identifies novel virulence determinants.  

PubMed

The virulence of bacterial pathogens is a complex process that requires the dynamic expression of many genes for the pathogens to invade and circumvent host defenses, as well as to proliferate in vivo. In this study, we employed a large-scale screen, signature-tagged mutagenesis (STM), to identify Streptococcus pyogenes virulence genes important for pathogenesis within the host. Approximately 1,200 STM mutants were created and screened using the zebrafish infectious disease model. The transposon insertion site was identified for 29 of the 150 mutants that were considered attenuated for virulence. Previously reported streptococcal virulence genes, such as mga, hasA, amrA, smeZ, and two genes in the sil locus, were identified, confirming the utility of the model for revealing genes important for virulence. Multiple genes not previously implicated in virulence were also identified, including genes encoding putative transporters, hypothetical cytosolic proteins, and macrolide efflux pumps. The STM mutant strains display various levels of attenuation, and multiple separate insertions were identified in either the same gene or the same locus, suggesting that these factors are important for this type of acute, invasive infection. We further examined two such genes, silB and silC of a putative quorum-sensing regulon, and determined that they are significant virulence factors in our model of necrotizing fasciitis. sil locus promoter expression was examined under various in vitro conditions, as well as in zebrafish tissues, and was found to be differentially induced. This study was a unique investigation of S. pyogenes factors required for successful invasive infection. PMID:19223485

Kizy, Anne E; Neely, Melody N

2009-02-17

77

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

PubMed Central

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.

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

2011-01-01

78

Growth Phase-Dependent Effect of Clindamycin on Production of Exoproteins by Streptococcus pyogenes?  

PubMed Central

The administration of high-dose clindamycin plus benzylpenicillin has been recommended for the treatment of streptococcal toxic shock-like syndrome caused by Streptococcus pyogenes, and clindamycin has been found to be more effective than beta-lactams in retrospective analyses of human cases. Although therapeutic doses of clindamycin have also been shown to be effective against experimental infections and clindamycin has great efficacy against the production of bacterial exoproteins, we recently reported that the level of production of some exoproteins was unchanged or even increased by a subinhibitory dose of clindamycin when it is added upon the initiation of bacterial culture and the treated cultures were analyzed by two-dimensional gel electrophoresis. In this study we further examined the effect of clindamycin on the production of exoproteins by adding it to Streptococcus pyogenes cultures during various growth phases. We found that the levels of production of some proteins, NAD+ glycohydrolase, streptolysin O, and streptococcal inhibitor of complement, were increased when clindamycin was added at early-log-phase growth, which was the result that was seen when clindamycin was added at the beginning of culture. However, clindamycin inhibited the production of most types of proteins when it was administered to Streptococcus pyogenes cultures at mid-log-phase growth. In csrS- or mga-knockout bacterial strains, the increase in exoproteins seen in parental strains was considerably inhibited. Our study indicates that the in vitro effect of clindamycin on the production of exoproteins greatly depends on the growth phase of bacteria and some regulatory factors of Streptococcus pyogenes that are involved in this phenomenon.

Sawai, Jun; Hasegawa, Tadao; Kamimura, Takuya; Okamoto, Akira; Ohmori, Daisuke; Nosaka, Nobuyuki; Yamada, Keiko; Torii, Keizo; Ohta, Michio

2007-01-01

79

Chemokines are secreted by monocytes following OK432 (lyophilized Streptococcus pyogenes) stimulation  

Microsoft Academic Search

BACKGROUND: OK-432, penicillin-killed Streptococcus pyogenes, is used in treating lymphangiomas and carcinomas. We have studied in vitro the role of mononuclear phagocytes (MNPs), including purified monocytes (MOs), in the immune response to OK-432. MIP-1?\\/? and MCP-1 secretions were assessed in whole blood (WB), peripheral blood mononuclear cells (PBMCs) and purified MOs, after in vitro stimulation with OK-432 with or without

Carla Olsnes; Helen Stavang; Karl Brokstad; Jan Olofsson; Hans J Aarstad

2009-01-01

80

Macrolide Resistance in Streptococcus pyogenes Isolates from Throat Infections in the Region of Aachen, Germany  

Microsoft Academic Search

Macrolide-resistance was assessed in 216 consecutive Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany. Seventeen isolates were resistant to erythromycin: 12 isolates revealed a macrolide (M) phenotype and harbored mefA, and five strains expressed an inducible macrolide-lincosamide- streptogramin B (MLS B) phenotype of which four strains harbored ermA(TR) and one strain contained ermB(AM). Telithromycin (HMR 3647)

C. M. Brandt; M. Honscha; N. D. Truong; R. Holland; B. Hovener; A. Bryskier; R. Lutticken; R. R. Reinert

2001-01-01

81

Aerotolerance and Peroxide Resistance in Peroxidase and PerR Mutants of Streptococcus pyogenes  

Microsoft Academic Search

Survival in aerobic conditions is critical to the pathogenicity of many bacteria. To investigate the means of aerotolerance and resistance to oxidative stress in the catalase-negative organism Streptococcus pyogenes ,w e used a genomics-based approach to identify and inactivate homologues of two peroxidase genes, encoding alkyl hydroperoxidase (ahpC) and glutathione peroxidase (gpoA). Single and double mutants survived as well as

KATHERINE Y. KING; JOSHUA A. HORENSTEIN; MICHAEL G. CAPARON

2000-01-01

82

Replication origin of Streptococcus pyogenes, organization and cloning in heterologous systems  

Microsoft Academic Search

The origin of DNA replication (oriC) of Streptococcus pyogenes, group A streptococci (GAS), has been cloned in Escherichia coli and reintroduced by transformation into other GAS strains. Transformation frequencies into GAS strains with oriC-carrying plasmids occurred with unusually high frequencies. However, the oriC-containing plasmids in the new recipients were found to be unstable and had a tendency to integrate into

Alexander N. Suvorov; Joseph J. Ferretti

2000-01-01

83

Anionic Lipids Enriched at the ExPortal of Streptococcus pyogenes  

Microsoft Academic Search

The ExPortal of Streptococcus pyogenes is a membrane microdomain dedicated to the secretion and folding of proteins. We investigated the lipid composition of the ExPortal by examining the distribution of anionic membrane phospholipids. Staining with 10-N-nonyl-acridine orange revealed a single microdomain enriched with an anionic phospholipid whose staining characteristics and behavior in a cardiolipin-deficient mutant were characteristic of phosphatidylglycerol. Furthermore,

Jason W. Rosch; Fong Fu Hsu; Michael G. Caparon

2007-01-01

84

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

PubMed Central

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.

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

2009-01-01

85

An Association Between Peptidoglycan Synthesis and Organization of the Streptococcus pyogenes ExPortal.  

PubMed

ABSTRACT The ExPortal of Streptococcus pyogenes is a focal microdomain of the cytoplasmic membrane that clusters the translocons of the general secretory pathway with accessory factors to facilitate the maturation of secreted polypeptides. While it is known that the ExPortal is enriched in anionic lipids, the mechanisms that organize the ExPortal are poorly understood. In the present study, we examined the role of the cell wall in organizing and maintaining the ExPortal. Removal of the cell wall resulted in a loss of ExPortal focal integrity accompanied by the circumferential redistribution of ExPortal lipid and protein components. A similar loss occurred upon treatment with gallidermin, a nonpermeabilizing lantibiotic that targets the lipid II precursor of peptidoglycan synthesis, and this treatment disrupted the secretion of several ExPortal substrates. Furthermore, several enzymes involved in the membrane-associated steps of lipid II synthesis, including MraY and MurN, were found to localize to a single discrete focus in the membrane that was coincident with the focal location of the secretory translocons and the anionic lipid microdomain. These data suggest that the ExPortal is associated with the site of peptidoglycan precursor synthesis and that peptidoglycan biogenesis influences ExPortal organization. These data add to an emerging literature indicating that cell wall biogenesis, cell division, and protein secretion are spatially coorganized processes. IMPORTANCE Since Gram-positive bacteria lack a periplasmic space, they lack a protected compartment to spatially coordinate interaction between newly secreted proteins and the factors required to process them. This represents a significant problem for pathogens that depend on the secretion of toxins and cell wall-associated adhesins to cause disease. Streptococci solve this dilemma by restricting secretion and processing factors to a defined region of the membrane. However, the mechanisms that promote restriction are not understood. In this study, we show that restriction of these factors in the pathogen Streptococcus pyogenes is intimately linked with the presence of the cell wall and its synthesis. Furthermore, several cell wall synthesis proteins are also restricted to the site of protein secretion. This study contributes to our understanding of how the Gram-positive cell is organized to coordinate protein secretion and biogenesis with cell wall synthesis and to the ongoing development of antibiotics that target these processes. PMID:24065630

Vega, Luis Alberto; Port, Gary C; Caparon, Michael G

2013-09-24

86

Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen–host interactions  

Microsoft Academic Search

Streptococcus pyogenes (group A streptococcus, GAS) is a very important human pathogen with remarkable adaptation capabilities. Survival within the harsh host surroundings requires sensing potential on the bacterial side, which leads in particular to coordinately regulated virulence factor expression. GAS ‘stand-alone’ response regulators (RRs) and two-component signal transduction systems (TCSs) link the signals from the host environment with adaptive responses

Bernd Kreikemeyer; Kevin S. McIver; Andreas Podbielski

2003-01-01

87

Transcriptional activation of sclA by Mga requires a distal binding site in Streptococcus pyogenes.  

PubMed

Streptococcus pyogenes (the group A streptococcus [GAS]) is a medically significant pathogen of humans, causing a range of diseases from pharyngitis to necrotizing fasciitis. Several important GAS virulence genes are under the control of a pleiotropic regulator called Mga, or the multiple gene regulator of GAS, including the gene encoding the streptococcal collagen-like protein, or sclA. Analysis of the genome sequence upstream of sclA revealed two potential Mga-binding sites with homology to the published Mga-binding element, which were called PsclA-I (distal) and PsclA-II (proximal) based on their location relative to a predicted start of transcription. Primer extension was used to confirm that the Mga-dependent transcriptional start site for sclA was located adjacent to the proximal PsclA-II binding site. By using overlapping PsclA promoter probes and purified Mga-His fusion protein, it was shown by electrophoretic mobility shift assays that, unlike other Mga-regulated promoters, Mga binds only to a distal DNA-binding site (PsclA-I). Binding of Mga to PsclA-I could be competed with cold probes corresponding to known Mga-regulated promoters (Pemm, PscpA, and Pmga) but not with a nonspecific probe or the proximal PsclA-II fragment. With the use of a plasmid-based green fluorescent protein transcriptional reporter system, the full-length PsclA was not sufficient to reproduce normal Mga-regulated activation. However, studies using a single-copy gusA transcriptional reporter system integrated at the native sclA chromosomal locus clearly demonstrated that the distal PsclA-I binding site is required for Mga regulation. Therefore, PsclA represents a new class of Mga-regulated promoters that requires a single distal binding site for activation. PMID:15547255

Almengor, Audry C; McIver, Kevin S

2004-12-01

88

Fulminant necrotizing soft tissue infections due to Streptococcus pyogens  

Microsoft Academic Search

Aim-Background  Necrotizing soft tissue infection (NSTI) is a rapidly progressive soft tissue infection with high morbidity and mortality\\u000a rates. It has an incidence of approximately 1000 cases per year in the United States. Severe invasive group A Streptococcus\\u000a infections associated with bacteraemia and septic shock have occurred with increasing incidence. Early recognition and prompt\\u000a medical and surgical intervention are necessary to

Ch. Kontovounisios; M. Korontzi; V. Armoutidis; T. Papakonstantinou; G. Sgourakis; S. Lanitis

2010-01-01

89

Fluoroquinolone Resistance in Invasive Streptococcus pyogenes Isolates Due to Spontaneous Mutation and Horizontal Gene Transfer  

PubMed Central

Fluoroquinolone resistance in Streptococcus pyogenes has been described only anecdotally. In this study we describe two invasive ciprofloxacin-resistant S. pyogenes isolates (ciprofloxacin MICs, 8 mg/liter), one of which shows evidence of interspecies recombination. The quinolone resistance-determining regions of gyrA and parC were sequenced. In both isolates, there was no evidence for an efflux pump and no mutation in gyrA. Both isolates had an S79F mutation in parC that is known to confer fluoroquinolone resistance. In addition, a D91N mutation in parC, which is not related to fluoroquinolone resistance but is a feature of the parC sequence of Streptococcus dysgalactiae, was found in one isolate. The parC nucleotide sequence of that isolate showed greater diversity than that of S. pyogenes. A GenBank search and phylogenetic analysis suggest that this isolate acquired resistance by horizontal gene transfer from S. dysgalactiae. Statistical testing for recombination confirmed interspecies recombination of a 90-bp sequence containing the S79F mutation from S. dysgalactiae. For the other isolate, we could confirm that it acquired resistance by spontaneous mutation by identifying the susceptible ancestor in an outbreak setting.

Pletz, M. W. R.; McGee, L.; Van Beneden, C. A.; Petit, S.; Bardsley, M.; Barlow, M.; Klugman, K. P.

2006-01-01

90

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

PubMed Central

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.

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

2012-01-01

91

Absorption of kininogen from human plasma by Streptococcus pyogenes is followed by the release of bradykinin.  

PubMed Central

H-kininogen (high-molecular-mass kininogen, HK) is the precursor of the vasoactive peptide hormone bradykinin (BK). Previous work has demonstrated that HK binds to Streptococcus pyogenes through M-proteins, fibrous surface proteins and important virulence factors of these bacteria. Here we find that M-protein-expressing bacteria absorb HK from human plasma. The HK bound to the bacteria was found to be cleaved, and analysis of the degradation pattern suggested that the cleavage of HK at the bacterial surface is associated with the release of BK. Moreover, addition of activated plasma prekallikrein to bacteria preincubated with human plasma, resulted in BK release. This mechanism, by which a potent vasoactive and proinflammatory peptide is generated at the site of infection, should influence the host-parasite relationship during S. pyogenes infections.

Ben Nasr, A; Herwald, H; Sjobring, U; Renne, T; Muller-Esterl, W; Bjorck, L

1997-01-01

92

Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis  

Microsoft Academic Search

Streptococcus pyogenes is the bacterium most frequently isolated from patients with pharyngitis. Although various antibiotics including penicillin are effective, antibiotic treatment failure in cases of streptococcal pharyngitis have been reported. Herein, we investigated mechanisms associated with recurrent streptococcal pharyngitis. Clinically isolated S. pyogenes strains showed serotype-specific features, with emm12 strains most frequently detected and emm6 strains more likely to produce biofilm.

Taiji Ogawa; Yutaka Terao; Hisashi Okuni; Keiko Ninomiya; Hiroshi Sakata; Kazunori Ikebe; Yoshinobu Maeda; Shigetada Kawabata

2011-01-01

93

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

PubMed Central

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.

Mashburn-Warren, Lauren; Morrison, Donald A.

2012-01-01

94

Structural characterization and biological implications of di-zinc binding in the ferroxidase center of Streptococcus pyogenes Dpr.  

PubMed

Dps proteins contain a ferroxidase site that binds and oxidizes iron, thereby preventing hydroxyl radical formation by Fenton reaction. Although the involvement of a di-iron ferroxidase site has been suggested, X-ray crystal structures of various Dps members have shown either one or two iron cations with various occupancies despite the high structural conservation of the site. Similarly, structural studies with zinc, a redox-stable replacement for iron, have shown the binding of either one or two zinc ions. Here, the crystal structure of Streptococcus pyogenes Dpr in complex with zinc reveals the binding of two zinc cations in the ferroxidase center and an additional zinc-binding site at the surface of the protein. The results suggest a structural basis for the protection of Streptococcus pyogenes in zinc stress conditions and provide a clear evidence for a di-zinc and di-iron ferroxidase site in Streptococcus pyogenes Dpr protein. PMID:20599728

Haikarainen, Teemu; Tsou, Chih-Cheng; Wu, Jiunn-Jong; Papageorgiou, Anastassios C

2010-06-19

95

Identification and Cluster Analysis of Streptococcus pyogenes by MALDI-TOF Mass Spectrometry  

PubMed Central

Background Whole-cell matrix–assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been successfully applied for bacterial identification and typing of many pathogens. The fast and reliable qualities of MALDI-TOF MS make it suitable for clinical diagnostics. MALDI-TOF MS for the identification and cluster analysis of Streptococcus pyogenes, however, has not been reported. The goal of our study was to evaluate this approach for the rapid identification and typing of S. pyogenes. Methods 65 S. pyogenes isolates were obtained from the hospital. The samples were prepared and MALDI-TOF MS measurements were conducted as previously reported. Identification of unknown spectra was performed via a pattern recognition algorithm with a reference spectra and a dendrogram was constructed using the statistical toolbox in Matlab 7.1 integrated in the MALDI Biotyper 2.0 software. Results For identification, 61 of 65 S. pyogenes isolates could be identified correctly by MALDI-TOF MS with BioType 2.0 when compared to biochemical identification (API Strep), with an accuracy of 93.85%. In clustering analysis, 44 of 65 isolates were in accordance with those established by M typing, with a matching rate of 67.69%. When only the M type prevalence in China was considered, 41 of 45 isolates were in agreement with M typing, with a matching rate of 91.1%. Conclusions It was here shown that MALDI-TOF MS with Soft Biotype 2.0 and its database could facilitate rapid identification of S. pyogenes. It may present an attractive alternative to traditional biochemical methods of identification. However, for classification, more isolates and advances in the MALDI-TOF MS technology are needed to improve accuracy.

Hao, Huaijie; Kang, Lin; Zheng, Yuling; Jiang, Yongqiang; Jiang, Hua

2012-01-01

96

The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from Streptococcus pyogenes  

PubMed Central

Background 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. Results 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. Conclusions 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.

2009-01-01

97

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

PubMed Central

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.

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

2012-01-01

98

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

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

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

2013-07-25

99

Effect of SpeB and EndoS from Streptococcus pyogenes on Human Immunoglobulins  

PubMed Central

Streptococcus pyogenes secretes a specific immunoglobulin G (IgG)-protease, SpeB, as well as the IgG glycan-hydrolyzing enzyme EndoS. Here we show that SpeB also degrades IgA, IgM, IgD, and IgE. We also show that EndoS only hydrolyzes the glycan moiety on native but not denatured IgG. Thus, SpeB has a broad immunoglobulin-degrading activity, while EndoS is highly specific for IgG.

Collin, Mattias; Olsen, Arne

2001-01-01

100

M Protein GeneTypingofStreptococcus pyogenes by Nonradioactively Labeled Oligonucleotide Probes  

Microsoft Academic Search

A new approach forthetyping ofStreptococcus pyogenes isdescribed. Oligonucleotide probesof30 nucleotides inlength were derived fromcurrently knownsequencesoftheN-terminal regions ofM protein genes(emmgenes). Theoligonucleotides were labeled withdigoxigenin-dUTP andhybridized todot-blotted genomic DNA from116groupA streptococcal strains ofserotypes M-1,M-2,M-3,M-5,M-6,M-12,M-18, M-19,M-24,andM-49.Hybridization reactions were visualized witha chemiluminescent substrate. In comparison withconventional serological typing ofexpressed M proteins, thebinding oftheprobes tothe corresponding emm genesexhibited 100%sensitivity andspecificity. Theresults emphasize thehighdegree of type-specific

ACHIM KAUFHOLD; ANDREAS PODBIELSKI; DWIGHT R. JOHNSON; EDWARD L. KAPLAN; RUDOLF LUJTICKEN

1992-01-01

101

Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins.  

PubMed

Streptococcus pyogenes secretes a specific immunoglobulin G (IgG)-protease, SpeB, as well as the IgG glycan-hydrolyzing enzyme EndoS. Here we show that SpeB also degrades IgA, IgM, IgD, and IgE. We also show that EndoS only hydrolyzes the glycan moiety on native but not denatured IgG. Thus, SpeB has a broad immunoglobulin-degrading activity, while EndoS is highly specific for IgG. PMID:11598100

Collin, M; Olsén, A

2001-11-01

102

Emergence of Ciprofloxacin-Nonsusceptible Streptococcus pyogenes Isolates from Healthy Children and Pediatric Patients in Portugal?  

PubMed Central

We describe 66 ciprofloxacin-nonsusceptible Streptococcus pyogenes isolates recovered from colonized and infected children. The ParC S79A substitution was frequent and associated with the emm6/sequence type 382 (emm6/ST382) lineage. The ParC D83G substitution was detected in two isolates (emm5/ST99 and emm28/ST52 lineages). One isolate (emm89/ST101) had no quinolone resistance-determining region codon substitutions or other resistance mechanisms. Five of 66 isolates were levofloxacin resistant. Although fluoroquinolones are not used in children, they may be putative disseminators of fluoroquinolone-nonsusceptible strains in the community.

Pires, Renato; Ardanuy, Carmen; Rolo, Dora; Morais, Ana; Brito-Avo, Antonio; Goncalo-Marques, Jose; Linares, Josefina; Santos-Sanches, Ilda

2010-01-01

103

Emergence of ciprofloxacin-nonsusceptible Streptococcus pyogenes isolates from healthy children and pediatric patients in Portugal.  

PubMed

We describe 66 ciprofloxacin-nonsusceptible Streptococcus pyogenes isolates recovered from colonized and infected children. The ParC S79A substitution was frequent and associated with the emm6/sequence type 382 (emm6/ST382) lineage. The ParC D83G substitution was detected in two isolates (emm5/ST99 and emm28/ST52 lineages). One isolate (emm89/ST101) had no quinolone resistance-determining region codon substitutions or other resistance mechanisms. Five of 66 isolates were levofloxacin resistant. Although fluoroquinolones are not used in children, they may be putative disseminators of fluoroquinolone-nonsusceptible strains in the community. PMID:20350943

Pires, Renato; Ardanuy, Carmen; Rolo, Dora; Morais, Ana; Brito-Avô, António; Gonçalo-Marques, José; Lińares, Josefina; Santos-Sanches, Ilda

2010-03-29

104

A new closed-tube multiplex real-time PCR to detect eleven superantigens of Streptococcus pyogenes identifies a strain without superantigen activity.  

PubMed

Superantigens (SAgs) are very potent microbial toxins that are involved in severe diseases such as necrotizing fasciitis and toxic shock syndrome. There are currently 11 different SAgs that have been identified from Streptococcus pyogenes. In the present study, two sets of multiplex PCRs were developed for detection of these 11 SAg genes. The first group comprises spea1-3+5, spec, speg, spej, spek, and spel. The second group consists of spea1-4, speh, spei, spem, ssa, and smez. The presence of Streptococcus pyogenes SAg genes can be immediately identified using a real-time method with SYBR-Green, thus providing an excellent tool in clinical diagnostics. After testing more than 300 clinical isolates, we identified one strain without any SAg gene. This finding contrasts with previous reports describing SAg genes located on every Streptococcus pyogenes genome. This SAg gene-negative strain also did not show any mitogenic activity. It is hypothesized that clinical isolates from patients may overrepresent bacterial strains with pathogenic factors, such as SAgs. PMID:17481952

Lintges, Maria; Arlt, Sabine; Uciechowski, Peter; Plümäkers, Birgit; Reinert, Ralf R; Al-Lahham, Adnan; Lütticken, Rudolf; Rink, Lothar

2007-05-03

105

Evolution of transcription regulatory genes is linked to niche specialization in the bacterial pathogen Streptococcus pyogenes.  

PubMed

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of approximately 25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown. PMID:15937178

Bessen, Debra E; Manoharan, Anand; Luo, Feng; Wertz, John E; Robinson, D Ashley

2005-06-01

106

Evolution of Transcription Regulatory Genes Is Linked to Niche Specialization in the Bacterial Pathogen Streptococcus pyogenes  

PubMed Central

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of ?25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown.

Bessen, Debra E.; Manoharan, Anand; Luo, Feng; Wertz, John E.; Robinson, D. Ashley

2005-01-01

107

Unraveling the Regulatory Network in Streptococcus pyogenes: the Global Response Regulator CovR Represses rivR Directly  

Microsoft Academic Search

The response regulator CovR acts as a master regulator of virulence in Streptococcus pyogenes by repressing transcription of approximately 15% of the group A streptococcus genome directly or indirectly. We demonstrate that phosphorylated CovR represses transcription of rivR directly by binding to conserved sequences located downstream from the promoter to block procession of RNA polymerase. This establishes the first link

Samantha A. Roberts; Gordon G. Churchward; June R. Scott

2007-01-01

108

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

PubMed Central

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.

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

109

Telithromycin and Quinupristin-Dalfopristin Resistance in Clinical Isolates of Streptococcus pyogenes: SMART Program 2001 Data  

PubMed Central

This study evaluated the current status of antimicrobial resistance in clinical isolates of Streptococcus pyogenes in Taiwan as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. In 2001, 419 different isolates of S. pyogenes, including 275 from respiratory secretions, 87 from wound pus, and 31 from blood, were collected from nine hospitals in different parts of Taiwan. MICs of 23 antimicrobial agents were determined at a central location by the agar dilution method. All of the isolates were susceptible to penicillin (MIC at which 90% of the isolates were inhibited [MIC90], ?0.03 ?g/ml), cefotaxime (MIC90, ?0.03 ?g/ml), cefepime (MIC90, 0.06 ?g/ml), meropenem (MIC90, ?0.03 ?g/ml), moxifloxacin (MIC90, 0.25 ?g/ml), vancomycin (MIC90, 0.5 ?g/ml), and linezolid (MIC90, 1 ?g/ml). Overall, 78% of isolates were not susceptible to erythromycin (54% were intermediate, and 24% were resistant), and 5% were not susceptible to clindamycin. Of the 101 erythromycin-resistant isolates, 80.2% exhibited the M phenotype (mefA gene positive), 18.9% exhibited the cMLS (constitutive resistance to macrolides-lincosamides-streptogramin B [MLS]) phenotype (ermB gene positive), and 1% exhibited the iMLS (inducible resistance to MLS) phenotype (ermB gene positive). Fluoroquinolones (sitafloxacin > moxifloxacin > ciprofloxacin = levofloxacin = gatifloxacin > gemifloxacin) demonstrated potent activity against nearly all of the isolates of S. pyogenes tested. Thirty-two isolates (8%) were not susceptible to quinupristin-dalfopristin. Seventeen percent of isolates had telithromycin MICs of ?1 ?g/ml, and all of these isolates exhibited erythromycin MICs of ?32 ?g/ml. The high prevalence of resistance to telithromycin (which is not available in Taiwan) limits its potential use in the treatment of S. pyogenes infections, particularly in areas with high rates of macrolide resistance.

Hsueh, Po-Ren; Teng, Lee-Jene; Lee, Chun-Ming; Huang, Wen-Kuei; Wu, Tsu-Lan; Wan, Jen-Hsien; Yang, Dine; Shyr, Jainn-Ming; Chuang, Yin-Ching; Yan, Jing-Jou; Lu, Jang-Jih; Wu, Jiunn-Jong; Ko, Wen-Chien; Chang, Feng-Yee; Yang, Yi-Chueh; Lau, Yeu-Jun; Liu, Yung-Ching; Leu, Hsieh-Shong; Liu, Cheng-Yi; Luh, Kwen-Tay

2003-01-01

110

Long-term survival of Streptococcus pyogenes in rich media is pH-dependent  

PubMed Central

The mechanisms that allow Streptococcus pyogenes to survive and persist in the human host, often in spite of antibiotic therapy, remain poorly characterized. Therefore, the determination of culture conditions for long-term studies is crucial to advancement in this field. Stationary cultures of S. pyogenes strain NZ131 and its spontaneous small-colony variant OK171 were found to survive in rich medium for less than 2 weeks, and this inability to survive resulted from the acidification of the medium to below pH 5.5, which the cells did not tolerate for longer than 6–7 days. The growth of NZ131 resulted in acidification of the culture to below pH 5.5 by the onset of stationary phase, and the loss of viability occurred in a linear fashion. These results were also found to be true for M49 strain CS101 and for M1 strain SF370. The S. pyogenes strains could be protected from killing by the addition of a buffer that stabilized the pH of the medium at pH 6.5, ensuring bacterial survival to at least 70 days. By contrast, increasing the glucose added to the medium accelerated the loss of culture viability in strain NZ131 but not OK171, suggesting that the small-colony variant is altered in glucose uptake or metabolism. Similarly, acidification of the medium prior to inoculation or at the middle of exponential phase resulted in growth inhibition of all strains. These results suggest that control of the pH is crucial for establishing long-term cultures of S. pyogenes.

McShan, William M.

2012-01-01

111

Genomic Localization of a T Serotype Locus to a Recombinatorial Zone Encoding Extracellular Matrix-Binding Proteins in Streptococcus pyogenes  

PubMed Central

Streptococcus pyogenes is an important bacterial pathogen afflicting humans. A striking feature is its extraordinary biological diversity, evident in the wide range of diseases it can cause and the antigenic heterogeneity present on its surface. The T antigens form the basis of a major serological typing scheme that is often used as an alternative or supplement to M typing. Unlike M typing, the genetic basis for T typing is poorly understood. In this report, the tee6 gene is localized to a position ?3.3 kb downstream from prtF1 (or sfbI), which encodes the Fn-binding protein, protein F, a key virulence factor. Comparison of this portion of the genome with those of four additional strains reveals the presence of genes encoding a collagen-binding protein (Cpa) and a second Fn-binding protein (PrtF2 or PfbpI). This chromosomal region—here designated the FCT region—is ?11 to 16 kb in length and is flanked at both ends by long stretches of highly conserved sequence. For each of the five strains, the FCT region contains a unique combination of semiconserved loci, indicative of extensive intergenomic recombination. The data provide evidence that the highly recombinatorial FCT region of the S. pyogenes genome is under strong selection for change in response to the host environment.

Bessen, Debra E.; Kalia, Awdhesh

2002-01-01

112

A genetic exploration reveals novel Streptococcus pyogenes virulence factors important for in vivo survival and biofilm formation  

Microsoft Academic Search

Streptococcus pyogenes is an important human pathogen that can respond and adapt to changing environments. Although in vitro analyses have proven invaluable in determining specific streptococcal virulence factors, such studies are limited in their ability to provide a natural environment in which the invading pathogen responds directly, as well as indirectly, to the host conditions and defense systems. The goal

Anne E Kizy

2008-01-01

113

Survey of emm Gene Sequences from Pharyngeal Streptococcus pyogenes Isolates Collected in Spain and Their Relationship with Erythromycin Susceptibility  

Microsoft Academic Search

We conducted a nationwide survey of the variable 5 emm (M protein gene) sequences from 614 pharyngeal Streptococcus pyogenes isolates susceptible (299 isolates) and resistant (315 isolates) to erythromycin that were isolated in Spain from 1996 to 1999. Almost 98% of these isolates had emm sequences in agreement with previously recorded M antigen association. We only identified a new 5

Sebastian Albertí; Lorenzo Aguilar; Emilia Cercenado; Miguel Gobernado; Adela García-Perea; Gregorio Maranon

2003-01-01

114

Draft genome sequences of two Streptococcus pyogenes strains involved in abnormal sharp raised scarlet fever in China, 2011.  

PubMed

A scarlet fever outbreak caused by Streptococcus pyogenes occurred in China in 2011. To determine the genomic features of the outbreak strains, we deciphered genomes of two strains isolated from the regions with the highest incidence rates. The sequences will provide valuable information for comprehensive study of mechanisms related to this outbreak. PMID:23045496

You, Yuanhai; Yang, Xianwei; Song, Yanyan; Yan, Xiaomei; Yuan, Yanting; Li, Dongfang; Yan, Yanfeng; Wang, Haibin; Tao, Xiaoxia; Li, Leilei; Jiang, Xihong; Zhou, Hao; Xiao, Di; Jin, Lianmei; Feng, Zijian; Yang, Ruifu; Luo, Fengji; Cui, Yujun; Zhang, Jianzhong

2012-11-01

115

An Iron-Binding Protein, Dpr, Decreases Hydrogen Peroxide Stress and Protects Streptococcus pyogenes against Multiple Stresses  

Microsoft Academic Search

Streptococcus pyogenes does not produce catalase, but it can grow in aerobic environments and survive in the presence of peroxide. One of the stress proteins of this organism, peroxide resistance protein (Dpr), has been studied to examine its role in resistance to hydrogen peroxide, but the protective mechanism of Dpr is not clear. The aim of this study was to

Chih-Cheng Tsou; Chuan Chiang-Ni; Yee-Shin Lin; Woei-Jer Chuang; M.-T. Lin; C.-C. Liu; J.-J. Wu

2008-01-01

116

Draft Genome Sequences of Two Streptococcus pyogenes Strains Involved in Abnormal Sharp Raised Scarlet Fever in China, 2011  

PubMed Central

A scarlet fever outbreak caused by Streptococcus pyogenes occurred in China in 2011. To determine the genomic features of the outbreak strains, we deciphered genomes of two strains isolated from the regions with the highest incidence rates. The sequences will provide valuable information for comprehensive study of mechanisms related to this outbreak.

You, Yuanhai; Yang, Xianwei; Song, Yanyan; Yan, Xiaomei; Yuan, Yanting; Li, Dongfang; Yan, Yanfeng; Wang, Haibin; Tao, Xiaoxia; Li, Leilei; Jiang, Xihong; Zhou, Hao; Xiao, Di; Jin, Lianmei; Feng, Zijian; Yang, Ruifu; Luo, Fengji

2012-01-01

117

Rapid Development of Brain Abscess Caused by Streptococcus Pyogenes Following Penetrating Skull Injury via the Ethmoidal Sinus and Lamina Cribrosa  

PubMed Central

Objective Streptococcus pyogenes is a beta-hemolytic bacterium that belongs to Lancefield serogroup A, also known as group A streptococci (GAS). There have been five reported case in terms of PubMed-based search but no reported case of brain abscess caused by Streptococcus pyogenes as a result of penetrating skull injury. We present a patient who suffered from penetrating skull injury that resulted in a brain abscess caused by Streptococcus pyogenes. Methods The patient was a 12-year-old boy who fell down from his bicycle while cycling and ran into a tree. A wooden stick penetrated his skin below the right lower eyelid and advanced to the cranium. He lost consciousness on the fifth day of the incident and his body temperature was measured as 40?. While being admitted to our hospital, a cranial computed tomography revealed a frontal cystic mass with a perilesional hypodense zone of edema. There was no capsule formation around the lesion after intravenous contrast injection. Paranasal CT showed a bone defect located between the ethmoidal sinus and lamina cribrosa. Results Bifrontal craniotomy was performed. The abscess located at the left frontal lobe was drained and the bone defect was repaired. Conclusion Any penetrating lesion showing a connection between the lamina cribrosa and ethmoidal sinus may result in brain abscess caused by Streptococcus pyogenes. These patients should be treated urgently to repair the defect and drain the abscess with appropriate antibiotic therapy started due to the fulminant course of the brain abscess caused by this microorganism.

Aydin, Gerilmez; Comert, Serhat; Altinors, Nur

2010-01-01

118

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

Microsoft Academic Search

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 naďve approach that examines the preferential nucleotide usage along the chromosome, namely the usage of

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

2009-01-01

119

Characterization of macrolide efflux pump mef subclasses detected in clinical isolates of Streptococcus pyogenes isolated between 1999 and 2005.  

PubMed

The macrolide efflux mechanism of resistance, mef, was characterized in community-acquired respiratory tract infections with Streptococcus pyogenes. Fifty-four (4.6%) M phenotype isolates were screen tested as negative for mef(A). Of these 54 isolates, 5 (0.4%), 27 (2.3%), and 1 (0.1%) were considered to be mef(I) positive, a novel mosaic variant of mef, or a novel subclass of mef, respectively. This study shows (i) the definitive presence of mef(E) in S. pyogenes and its global distribution, (ii) the presence of a mosaic variant of mef composed of mef(A) and mef(E), (iii) the previously undescribed presence of mef(I) in S. pyogenes, and (iv) the presence of a novel subclass of mef in S. pyogenes. PMID:19258262

Blackman Northwood, J; Del Grosso, M; Cossins, L R; Coley, M D; Creti, R; Pantosti, A; Farrell, D J

2009-03-02

120

Salivaricin G32, a Homolog of the Prototype Streptococcus pyogenes Nisin-Like Lantibiotic SA-FF22, Produced by the Commensal Species Streptococcus salivarius  

PubMed Central

Salivaricin G32, a 2667?Da novel member of the SA-FF22 cluster of lantibiotics, has been purified and characterized from Streptococcus salivarius strain G32. The inhibitory peptide differs from the Streptococcus pyogenes—produced SA-FF22 in the absence of lysine in position 2. The salivaricin G32 locus was widely distributed in BLIS-producing S. salivarius, with 6 (23%) of 26 strains PCR-positive for the structural gene, slnA. As for most other lantibiotics produced by S. salivarius, the salivaricin G32 locus can be megaplasmid encoded. Another member of the SA-FF22 family was detected in two Streptococcus dysgalactiae of bovine origin, an observation supportive of widespread distribution of this lantibiotic within the genus Streptococcus. Since the inhibitory spectrum of salivaricin G32 includes Streptococcus pyogenes, its production by S. salivarius, either as a member of the normal oral microflora or as a commercial probiotic, could serve to enhance protection of the human host against S. pyogenes infection.

Wescombe, Philip A.; Dyet, Kristin H.; Dierksen, Karen P.; Power, Daniel A.; Jack, Ralph W.; Burton, Jeremy P.; Inglis, Megan A.; Wescombe, Anna L.; Tagg, John R.

2012-01-01

121

Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection  

PubMed Central

Streptococcus pyogenes is a leading cause of pharyngeal infection, with an estimated 616 million cases per year. The human nasopharynx represents the major reservoir for all S. pyogenes infection, including severe invasive disease. To investigate bacterial and host factors that influence S. pyogenes infection, we have devised an improved murine model of nasopharyngeal colonization, with an optimized dosing volume to avoid fulminant infections and a sensitive host strain. In addition we have utilized a refined technique for longitudinal monitoring of bacterial burden that is non-invasive thereby reducing the numbers of animals required. The model was used to demonstrate that the two component regulatory system, CovR/S, is required for optimum infection and transmission from the nasopharynx. There is a fitness cost conferred by covR/S mutation that is specific to the nasopharynx. This may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite possessing a selective advantage in invasive infection.

Alam, Faraz M.; Turner, Claire E.; Smith, Ken; Wiles, Siouxsie; Sriskandan, Shiranee

2013-01-01

122

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

PubMed

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 µg/ml) and one isolate was resistant to tetracycline (MIC= 16 µg/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

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

2013-04-01

123

Purification and Characterization of Streptin, a Type A1 Lantibiotic Produced by Streptococcus pyogenes  

PubMed Central

Approximately 10% of Streptococcus pyogenes strains inhibit the growth of all nine indicators in a standardized streptococcal bacteriocin typing scheme. The present study has shown that this inhibitory profile, referred to as bacteriocin producer (P)-type 777 activity, is due to the type A1 lantibiotic streptin. Two major forms of streptin were purified to homogeneity from 95% acidified (pH 2) methanol extracts of S. pyogenes M25 cells by using a series of reversed-phase chromatographic separations. The fully processed form of streptin (streptin 1) is a 23-amino-acid peptide with a mass of 2,424 Da. The 2,821-Mr form of the peptide (streptin 2) has three additional amino acids (TPY) at the N terminus. Strain M25 extracts also contained small quantities of the streptin 1 and streptin 2 peptides in various stages of dehydration. Streptin 1 and streptin 2 were each capable of specifically inducing streptin production when added to strain M25 cultures. The streptin gene cluster resembled that of other type A1 lantibiotics but appeared to lack a streptin-specific proteinase gene. Although the streptin structural gene (srtA) was widespread within S. pyogenes, being detected in 40 of 58 strains, each representing a different M serotype, only 10 of these srtA-positive strains produced active streptin. The failure of some strains to express streptin was attributed to an ?4.5-kb deletion in their streptin loci, encompassing genes putatively encoding proteins involved in streptin processing (srtB and srtC) and transport (srtT). In other strains, srtA transcription appeared to be defective. No direct association could be detected between the production of streptin and the production of the lantibiotic-like hemolysin streptolysin S in strain M25.

Wescombe, Philip A.; Tagg, John R.

2003-01-01

124

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

PubMed

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

Ludlam, H; Cookson, B

1986-08-01

125

Expression, purification and crystallization of the C-terminal LRR domain of Streptococcus pyogenes protein 0843.  

PubMed

Streptococcus pyogenes protein 0843 (Spy0843) is a recently identified protein with a potential adhesin function. Sequence analysis has shown that Spy0843 contains two leucine-rich repeat (LRR) domains that mediate interactions with the gp340 receptor. Here, the C-terminal LRR domain was overexpressed in Escherichia coli, purified and crystallized in the presence of 1.7-1.8?M ammonium sulfate pH 7.4 as precipitant. Data were collected from a single crystal to 1.59?Ĺ resolution at 100?K at a synchrotron-radiation source. The crystal was found to belong to space group I41, with unit-cell parameters a = b = 121.4, c = 51.5?Ĺ and one molecule in the asymmetric unit. Elucidation of the crystal structure will provide insights into the interactions of Spy0843 with the gp340 receptor and a better understanding of the role of Spy0843 in streptococcal infections. PMID:23695577

Haikarainen, Teemu; Loimaranta, Vuokko; Prieto-Lopez, Carlos; Battula, Pradeep; Finne, Jukka; Papageorgiou, Anastassios C

2013-04-30

126

SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines  

PubMed Central

Background CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP–10/CXCL10 and I–TAC/CXCL11, are antibacterial for Streptococcus pyogenes. Methodology/Principal Findings SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GRO?/CXCL1, GRO?/CXCL2, GRO?/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3?/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3?/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. Conclusions/Significance SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium.

Egesten, Arne; Olin, Anders I.; Linge, Helena M.; Yadav, Manisha; Morgelin, Matthias; Karlsson, Anna; Collin, Mattias

2009-01-01

127

Identification of pel, a Streptococcus pyogenes Locus That Affects both Surface and Secreted Proteins  

PubMed Central

A Tn917 insertion mutant of an M49 serotype, opacity factor-positive Streptococcus pyogenes, was isolated. It had the following phenotypes: decreased ?-hemolysis mediated by streptolysin S, reduction in the activity of a secreted cysteine protease and streptokinase, and an altered immunoglobulin and fibrinogen-binding phenotype. The site of insertion of Tn917 into the chromosome and the surrounding sequence, the pel region (pleiotropic effect locus), was determined. Phage A25 transduction confirmed that the pleiotropic changes in phenotype could be cotransduced with Tn917. The pel region was cloned and sequenced, and the transposon was found to be inserted upstream of a single open reading frame which led to a failure to transcribe a 500-base mRNA. The loss of this transcript decreased the transcription of emm and speB genes and reduced the secretion of streptokinase. Enhanced Pel expression from a nisin-inducible plasmid resulted in increased message levels for emm in a wild-type organism. Characterization of the pel mutant provides evidence for the coordinated regulation of secreted and surface proteins and suggests the existence of a new global regulatory factor in S. pyogenes.

Li, Zhuqing; Sledjeski, Darren D.; Kreikemeyer, Bernd; Podbielski, Andreas; Boyle, Michael D. P.

1999-01-01

128

Inactivated and live, attenuated influenza vaccines protect mice against influenza:Streptococcus pyogenes super-infections  

PubMed Central

Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with S. pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-? which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue to levels that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.

Chaussee, Michael S.; Sandbulte, Heather R.; Schuneman, Margaret J.; DePaula, Frank P.; Addengast, Leslie A.; Schlenker, Evelyn H.; Huber, Victor C.

2011-01-01

129

Intramolecular Isopeptide Bonds Give Thermodynamic and Proteolytic Stability to the Major Pilin Protein of Streptococcus pyogenes*  

PubMed Central

The pili expressed by Streptococcus pyogenes and certain other Gram-positive bacterial pathogens are based on a polymeric backbone in which individual pilin subunits are joined end-to-end by covalent isopeptide bonds through the action of sortase enzymes. The crystal structure of the major pilin of S. pyogenes, Spy0128, revealed that each domain of the two domain protein contained an intramolecular isopeptide bond cross-link joining a Lys side chain to an Asn side chain. In the present work, mutagenesis was used to create mutant proteins that lacked either one isopeptide bond (E117A, N168A, and E258A mutants) or both isopeptide bonds (E117A/E258A). Both the thermal stability and proteolytic stability of Spy0128 were severely compromised by loss of the isopeptide bonds. Unfolding experiments, monitored by circular dichroism, revealed a transition temperature Tm of 85 °C for the wild type protein. In contrast, mutants with only one isopeptide bond showed biphasic unfolding, with the domain lacking an isopeptide bond having a Tm that was ?30 °C lower than the unaltered domain. High resolution crystal structures of the E117A and N168A mutants showed that the loss of an isopeptide bond did not change the overall pilin structure but caused local disturbance of the protein core that was greater for E117A than for N168A. These effects on stability appear also to be important for pilus assembly.

Kang, Hae Joo; Baker, Edward N.

2009-01-01

130

Oral Erythromycin Prophylaxis against Streptococcus pyogenes Infection in Penicillin-Allergic Military Recruits: A Randomized Clinical Trial. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

Historically, military recruits have required benzathine penicillin G to prevent epidemics of Streptococcus pyogenes. In this randomized clinical trial, low-dose oral erythromycin was evaluated as an alternative for prophylaxis against group A,6-hemolytic...

J. Fujikawa J. P. Struewing K. C. Hyames E. L. Kaplan A. K. Tupponce

1992-01-01

131

Structure and Kinetic Investigation of Streptococcus pyogenes Family GH38 ?-Mannosidase  

PubMed Central

Background The enzymatic hydrolysis of ??mannosides is catalyzed by glycoside hydrolases (GH), termed ??mannosidases. These enzymes are found in different GH sequence–based families. Considerable research has probed the role of higher eukaryotic “GH38” ??mannosides that play a key role in the modification and diversification of hybrid N-glycans; processes with strong cellular links to cancer and autoimmune disease. The most extensively studied of these enzymes is the Drosophila GH38 ??mannosidase II, which has been shown to be a retaining ??mannosidase that targets both ??1,3 and ??1,6 mannosyl linkages, an activity that enables the enzyme to process GlcNAc(Man)5(GlcNAc)2 hybrid N-glycans to GlcNAc(Man)3(GlcNAc)2. Far less well understood is the observation that many bacterial species, predominantly but not exclusively pathogens and symbionts, also possess putative GH38 ??mannosidases whose activity and specificity is unknown. Methodology/Principal Findings Here we show that the Streptococcus pyogenes (M1 GAS SF370) GH38 enzyme (Spy1604; hereafter SpGH38) is an ??mannosidase with specificity for ??1,3 mannosidic linkages. The 3D X-ray structure of SpGH38, obtained in native form at 1.9 Ĺ resolution and in complex with the inhibitor swainsonine (Ki 18 µM) at 2.6 Ĺ, reveals a canonical GH38 five-domain structure in which the catalytic “–1” subsite shows high similarity with the Drosophila enzyme, including the catalytic Zn2+ ion. In contrast, the “leaving group” subsites of SpGH38 display considerable differences to the higher eukaryotic GH38s; features that contribute to their apparent specificity. Conclusions/Significance Although the in vivo function of this streptococcal GH38 ??mannosidase remains unknown, it is shown to be an ??mannosidase active on N-glycans. SpGH38 lies on an operon that also contains the GH84 hexosaminidase (Spy1600) and an additional putative glycosidase. The activity of SpGH38, together with its genomic context, strongly hints at a function in the degradation of host N- or possibly O-glycans. The absence of any classical signal peptide further suggests that SpGH38 may be intracellular, perhaps functioning in the subsequent degradation of extracellular host glycans following their initial digestion by secreted glycosidases.

Suits, Michael D. L.; Zhu, Yanping; Taylor, Edward J.; Walton, Julia; Zechel, David L.; Gilbert, Harry J.; Davies, Gideon J.

2010-01-01

132

Role of Serine/Threonine Phosphatase (SP-STP) in Streptococcus pyogenes Physiology and Virulence*  

PubMed Central

Reversible phosphorylation is the key mechanism regulating several cellular events in prokaryotes and eukaryotes. In prokaryotes, signal transduction is perceived to occur primarily via the two-component signaling system involving histidine kinases and cognate response regulators. Although an alternative regulatory pathway controlled by the eukaryote-type serine/threonine kinase (Streptococcus pyogenes serine/threonine kinase; SP-STK) has been shown to modulate bacterial growth, division, adherence, invasion, and virulence in group A Streptococcus (GAS; S. pyogenes), the precise role of the co-transcribing serine/threonine phosphatase (SP-STP) has remained enigmatic. In this context, this is the first report describing the construction and characterization of non-polar SP-STP mutants in two different strains of Type M1 GAS. The STP knock-out mutants displayed increased bacterial chain lengths in conjunction with thickened cell walls, significantly reduced capsule and hemolysin production, and restoration of the phenotypes postcomplementation. The present study also reveals important contribution of cognately regulated-reversible phosphorylation by SP-STK/SP-STP on two major response regulators of two-component systems, WalRK and CovRS. We also demonstrate a distinct role of SP-STP in terms of expression of surface proteins and SpeB in a strain-specific manner. Further, the attenuation of virulence in the absence of STP and its restoration only in the complemented strains that were generated by the use of a low copy plasmid and not by a high copy one emphasize not only the essential role of STP in virulence but also highlight the tightly regulated SP-STP/SP-STK-mediated cognate functions. SP-STP thus is an important regulator of GAS virulence and plays a critical role in GAS pathogenesis.

Agarwal, Shivani; Agarwal, Shivangi; Pancholi, Preeti; Pancholi, Vijay

2011-01-01

133

Strains of Streptococcus pyogenes from Severe Invasive Infections Bind HEp2 and HaCaT Cells More Avidly than Strains from Uncomplicated Infections  

PubMed Central

Epidemiologically unrelated Streptococcus pyogenes strains isolated from blood, throat, and skin were assayed for adherence to HEp2 and HaCaT cells. Invasive isolates showed significantly higher avidity for these cell lines than isolates from skin and throat. In general, S. pyogenes showed greater binding to HaCaT cells than to HEp2 cells.

Edwards, Mandy L; Fagan, Peter K.; Smith-Vaughan, Heidi; Currie, Bart J.; Sriprakash, Kadaba S.

2003-01-01

134

Inactivation of DltA Modulates Virulence Factor Expression in Streptococcus pyogenes  

PubMed Central

Background D-alanylated lipoteichoic acid is a virtually ubiquitous component of Gram-positive cell walls. Mutations in the dltABCD operon of numerous species exhibit pleiotropic effects, including reduced virulence, which has been attributed to increased binding of cationic antimicrobial peptides to the more negatively charged cell surface. In this study, we have further investigated the effects that mutating dltA has on virulence factor expression in Streptococcus pyogenes. Methodology/Principal Findings Isogenic ?dltA mutants had previously been created in two distinct M1T1 isolates of S. pyogenes. Immunoblots, flow cytometry, and immunofluorescence were used to quantitate M protein levels in these strains, as well as to assess their ability to bind complement. Bacteria were tested for their ability to interact with human PMN and to grow in whole human blood. Message levels for emm, sic, and various regulatory elements were assessed by quantitative RT-PCR. Cell walls of ?dltA mutants contained much less M protein than cell walls of parent strains and this correlated with reduced levels of emm transcripts, increased deposition of complement, increased association of bacteria with polymorphonuclear leukocytes, and reduced bacterial growth in whole human blood. Transcription of at least one other gene of the mga regulon, sic, which encodes a protein that inactivates antimicrobial peptides, was also dramatically reduced in ?dltA mutants. Concomitantly, ccpA and rofA were unaffected, while rgg and arcA were up-regulated. Conclusions/Significance This study has identified a novel mechanism for the reduced virulence of dltA mutants of Streptococcus pyogenes in which gene regulatory networks somehow sense and respond to the loss of DltA and lack of D-alanine esterification of lipoteichoic acid. The mechanism remains to be determined, but the data indicate that the status of D-alanine-lipoteichoic acid can significantly influence the expression of at least some streptococcal virulence factors and provide further impetus to targeting the dlt operon of Gram-positive pathogens in the search for novel antimicrobial compounds.

Cox, Kathleen H.; Ruiz-Bustos, Eduardo; Courtney, Harry S.; Dale, James B.; Pence, Morgan A.; Nizet, Victor; Aziz, Ramy K.; Gerling, Ivan; Price, Susan M.; Hasty, David L.

2009-01-01

135

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

PubMed Central

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.

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

2012-01-01

136

Characterization of Macrolide Efflux Pump mef Subclasses Detected in Clinical Isolates of Streptococcus pyogenes Isolated between 1999 and 2005  

Microsoft Academic Search

The macrolide efflux mechanism of resistance, mef, was characterized in community-acquired respiratory tract infections with Streptococcus pyogenes. Fifty-four (4.6%) M phenotype isolates were screen tested as negative for mef(A). Of these 54 isolates, 5 (0.4%), 27 (2.3%), and 1 (0.1%) were considered to be mef(I) positive, a novel mosaic variant of mef, or a novel subclass of mef, respectively. This

J. Blackman Northwood; M. Del Grosso; L. R. Cossins; M. D. Coley; R. Creti; A. Pantosti; D. J. Farrell

2009-01-01

137

Epidemiology and Molecular Characterization of Streptococcus pyogenes Recovered from Scarlet Fever Patients in Central Taiwan from 1996 to 1999  

Microsoft Academic Search

One hundred seventy-nine Streptococcus pyogenes isolates recovered from scarlet fever patients from 1996 to 1999 in central Taiwan were characterized by emm, Vir, and pulsed-field gel electrophoresis (PFGE) typing methods. The protocols for Vir and PFGE typing were standardized. A database of the DNA fingerprints for the isolates was established. Nine emm or emm-like genes, 19 Vir patterns, and 26

Chien-Shun Chiou; Tsai-Ling Liao; Tzu-Hui Wang; Hsiu-Li Chang; Jui-Cheng Liao; Chun-Chin Li

2004-01-01

138

Hydrogen Peroxide Production in Streptococcus pyogenes: Involvement of Lactate Oxidase and Coupling with Aerobic Utilization of Lactate  

Microsoft Academic Search

Streptococcus pyogenes strains can be divided into two classes, one capable and the other incapable of producing H2O2 (M. Saito, S. Ohga, M. Endoh, H. Nakayama, Y. Mizunoe, T. Hara, and S. Yoshida, Micro- biology 147:2469-2477, 2001). In the present study, this dichotomy was shown to parallel the presence or absence of H2O2-producing lactate oxidase activity in permeabilized cells. Both

Masanori Seki; Ken-ichiro Iida; Mitsumasa Saito; Hiroaki Nakayama; Shin-ichi Yoshida

2004-01-01

139

Phenotypes and Genotypes of Erythromycin-Resistant Streptococcus pyogenes Strains in Italy and Heterogeneity of Inducibly Resistant Strains  

Microsoft Academic Search

A total of 387 clinical strains of erythromycin-resistant (MIC, >1 mg\\/ml) Streptococcus pyogenes, all isolated in Italian laboratories from 1995 to 1998, were examined. By the erythromycin-clindamycin double-disk test, 203 (52.5%) strains were assigned to the recently described M phenotype, 120 (31.0%) were assigned to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS) phenotype, and 64 (16.5%) were assigned

ELEONORA GIOVANETTI; MARIA PIA MONTANARI; MARINA MINGOIA; PIETRO EMANUELE VARALDO

1999-01-01

140

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

Microsoft Academic Search

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 µg\\/ml to>3000 µg\\/ml for E. coli. An extract of transformed cells, particularly a high-salt ribosomal wash, contained an enzyme

Alexander N. Suvorov; Bob van Gemen; Peter H. van Knippenberg

1988-01-01

141

Genetic Elements Carrying erm(B) in Streptococcus pyogenes and Association with tet(M) Tetracycline Resistance Gene  

Microsoft Academic Search

This study was directed at characterizing the genetic elements carrying the methylase gene erm(B), encoding ribosome modification-mediated resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics, in Streptococcus pyogenes. In this species, erm(B) is responsible for MLS resistance in constitutively resistant isolates (cMLS phenotype) and in a subset (iMLS-A) of inducibly resistant isolates. A total of 125 erm(B)-positive strains were

Andrea Brenciani; Alessandro Bacciaglia; Manuela Vecchi; Luca A. Vitali; Pietro E. Varaldo; Eleonora Giovanetti

2007-01-01

142

MtsABC Is Important for Manganese and Iron Transport, Oxidative Stress Resistance, and Virulence of Streptococcus pyogenes  

Microsoft Academic Search

MtsABC is a Streptococcus pyogenes ABC transporter which was previously shown to be involved in iron and zinc accumulation. In this study, we showed that an mtsABC mutant has impaired growth, particularly in a metal-depleted medium and an aerobic environment. In metal-depleted medium, growth was restored by the addition of 10 M MnCl2, whereas other metals had modest or no

Robert Janulczyk; Susanna Ricci; Lars Bjorck

2003-01-01

143

Synergistic effect of green tea extract and probiotics on the pathogenic bacteria, Staphylococcus aureus and Streptococcus pyogenes  

Microsoft Academic Search

The aim of this study was to assess the effect of a commercial green tea extract (TEAVIGO™) on the microbial growth of three\\u000a probiotic strains (Lactobacillus and Bifidobacterium), as well as three pathogenic bacteria. MIC and co-culture studies were performed. The MICs of the green tea extract against\\u000a Staphylococcus aureus and Streptococcus pyogenes (100 ?g ml?1) were considerably lower than those against

Ping Su; Anders Henriksson; Christina Nilsson; Hazel Mitchell

2008-01-01

144

Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes  

Microsoft Academic Search

Adhesion of the serotype M1 Streptococcus pyogenes strain SF370 to human tonsil explants and cultured keratinocytes requires extended polymeric surface structures called pili.\\u000a In this important human pathogen, pili are assembled from three protein subunits: Spy0125, Spy0128 and Spy0130 through the\\u000a action of sortase enzymes. For this study, the structural properties of these pili proteins have been investigated in solution.

Alexandra S. Solovyova; Jonathan A. Pointon; Paul R. Race; Wendy D. Smith; Michael A. Kehoe; Mark J. Banfield

2010-01-01

145

Streptococcus pyogenes SpyCEP Influences Host-Pathogen Interactions during Infection in a Murine Air Pouch Model  

Microsoft Academic Search

Streptococcus pyogenes is a major human pathogen worldwide, responsible for both local and systemic infections. These bacteria express the subtilisin-like protease SpyCEP which cleaves human IL-8 and related chemokines. We show that localization of SpyCEP is growth-phase and strain dependent. Significant shedding was observed only in a strain naturally overexpressing SpyCEP, and shedding was not dependent on SpyCEP autoproteolytic activity.

Nico Chiappini; Anja Seubert; John L. Telford; Guido Grandi; Davide Serruto; Immaculada Margarit; Robert Janulczyk

2012-01-01

146

The RofA Binding Site in Streptococcus pyogenes Is Utilized in Multiple Transcriptional Pathways  

PubMed Central

Understanding the regulation of adhesins defines a pathogenic bacterium's interaction with the local environment within the host. In certain strains of Streptococcus pyogenes, transcription of prtF, the gene which encodes the fibronectin-binding adhesin protein F, is activated by RofA under anaerobic conditions. RofA binds specifically to DNA in its target promoters and autoregulates its own expression. In this study, we have used DNase I protection assays to further investigate the interaction of RofA with its target promoters. In the region between rofA and the gene which encodes protein F (prtF), RofA binds to two distinct sites: a smaller site (17 bp) adjacent to the rofA promoter, and a larger site (40 bp) adjacent to the prtF promoter. Analysis of fusions to a novel reporter gene whose product consists of the fusion of the N-terminal secretion domain of protein F with the C-terminal enzymatic domain of the enterococcal alkaline phosphatase (PhoZ) revealed that the small RofA binding site had no direct role in control of prtF transcription but contributed to regulation of rofA. Comparison in several strains representing different patterns of prtF expression indicated that the larger site was required for activation of rofA and of prtF in all strains by both RofA-dependent and -independent pathways. Thus, it would appear that a common recognition sequence provides separate entries to a final common pathway in S. pyogenes virulence gene expression. The identification of multiple RofA-like proteins and promoters with RofA binding sites implies the existence of a widespread interacting regulatory network.

Granok, Alexander B.; Parsonage, Derek; Ross, R. Paul; Caparon, Michael G.

2000-01-01

147

The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes.  

PubMed

Streptococcus pyogenes (GAS) is a human pathogen that causes pharyngitis and invasive diseases such as toxic shock syndrome and sepsis. The upper respiratory tract is the primary reservoir from which GAS can infect new hosts and cause disease. The factors involved in colonisation are incompletely known however. Previous evidence in oral streptococci has shown that the AgI/II family proteins are involved. We hypothesized that the AspA member of this family might be involved in GAS colonization. We describe a novel mouse model of GAS colonization of the nasopharynx and lower respiratory tract to elucidate these interactions. We used two clinical M serotypes expressing AspA, and their aspA gene deletant isogenic mutants in experiments using adherence assays to respiratory epithelium, macrophage phagocytosis and neutrophil killing assays and in vivo models of respiratory tract colonisation and infection. We demonstrated the requirement for AspA in colonization of the respiratory tract. AspA mutants were cleared from the respiratory tract and were deficient in adherence to epithelial cells, and susceptible to phagocytosis. Expression of AspA in the surrogate host Lactococcus lactis protected bacteria from phagocytosis. Our results suggest that AspA has an essential role in respiratory infection, and may function as a novel anti-phagocytic factor. PMID:23638083

Franklin, Linda; Nobbs, Angela H; Bricio-Moreno, Laura; Wright, Christopher J; Maddocks, Sarah E; Sahota, Jaspreet Singh; Ralph, Joe; O'Connor, Matthew; Jenkinson, Howard F; Kadioglu, Aras

2013-04-30

148

A Naturally Occurring Rgg Variant in Serotype M3 Streptococcus pyogenes Does Not Activate speB Expression Due to Altered Specificity of DNA Binding?  

PubMed Central

The transcriptional regulator Rgg of Streptococcus pyogenes is essential for expression of the secreted cysteine protease SpeB. Although all isolates of S. pyogenes possess the speB gene, not all of them produce the protein in vitro. In a murine model of infection, the absence of SpeB production is associated with invasive disease. We speculated that naturally occurring mutations in rgg, which would also abrogate SpeB production, may be present in invasive isolates of S. pyogenes. Examination of the inferred Rgg sequences available in public databases revealed that the rgg gene in strain MGAS315 (a serotype M3 strain associated with invasive disease) encodes a proline at amino acid position 103 (Rgg103P); in contrast, all other strains encode a serine at this position (Rgg103S). A caseinolytic assay and Western blotting indicated that strain MGAS315 does not produce SpeB in vitro. Gene-swapping experiments showed that the rgg gene of MGAS315 is solely responsible for the lack of SpeB expression. In contrast to Rgg103S, Rgg103P does not bind to the speB promoter in gel shift assays, which correlates with a lack of speB expression. Despite its inability to activate speB expression, Rgg103P retains the ability to bind to DNA upstream of norA and to influence its expression. Overall, this study illustrates how variation at the rgg locus may contribute to the phenotypic diversity of S. pyogenes.

Kappeler, Kyle V.; Anbalagan, Srivishnupriya; Dmitriev, Alexander V.; McDowell, Emily J.; Neely, Melody N.; Chaussee, Michael S.

2009-01-01

149

An Association Between Peptidoglycan Synthesis and Organization of the Streptococcus pyogenes ExPortal  

PubMed Central

ABSTRACT The ExPortal of Streptococcus pyogenes is a focal microdomain of the cytoplasmic membrane that clusters the translocons of the general secretory pathway with accessory factors to facilitate the maturation of secreted polypeptides. While it is known that the ExPortal is enriched in anionic lipids, the mechanisms that organize the ExPortal are poorly understood. In the present study, we examined the role of the cell wall in organizing and maintaining the ExPortal. Removal of the cell wall resulted in a loss of ExPortal focal integrity accompanied by the circumferential redistribution of ExPortal lipid and protein components. A similar loss occurred upon treatment with gallidermin, a nonpermeabilizing lantibiotic that targets the lipid II precursor of peptidoglycan synthesis, and this treatment disrupted the secretion of several ExPortal substrates. Furthermore, several enzymes involved in the membrane-associated steps of lipid II synthesis, including MraY and MurN, were found to localize to a single discrete focus in the membrane that was coincident with the focal location of the secretory translocons and the anionic lipid microdomain. These data suggest that the ExPortal is associated with the site of peptidoglycan precursor synthesis and that peptidoglycan biogenesis influences ExPortal organization. These data add to an emerging literature indicating that cell wall biogenesis, cell division, and protein secretion are spatially coorganized processes.

Vega, Luis Alberto; Port, Gary C.; Caparon, Michael G.

2013-01-01

150

Heparin-inhibitable basement membrane-binding protein of Streptococcus pyogenes.  

PubMed Central

Solubilized surface proteins of Streptococcus pyogenes serotype M6 were found by indirect immunofluorescence assays to bind selectively to proteoglycan-containing regions of basement membranes of kidney and cardiac muscle in vitro. Epithelial, endothelial, and interstitial cells were unstained. Binding of streptococcal protein to basement membranes was competitively inhibited by heparin and, to a lesser extent, by heparan sulfate. Weak inhibition was also observed with other glycosaminoglycans, including dermatan sulfate, chondroitin sulfate, and hyaluronic acid. Type IV collagen, gelatin, serum fibronectin, glucuronic acid, and a selection of monosaccharides had no significant effects on binding. The heparin-inhibitable basement membrane-binding protein was purified by affinity chromatography on heparin-Sepharose 6-B. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and urea dissociated the affinity-purified protein into two polypeptides of 9,000 and 15,000 mrs. Chemical analyses revealed that the purified protein was devoid of cysteine, amino and neutral sugars, and phosphate. Thus, the polypeptides are not glycosylated or complexed with trace amounts of lipoteichoic acid or polysaccharide. Binding of purified protein to tissue was determined by direct radioassay and indirect immunofluorescence and was inhibitable by heparin. Although the in vivo effects of this streptococcal component remain to be determined, its deposition on basement membranes in vitro supports the hypothesis that it contributes to the pathogenesis of poststreptococcal glomerulonephritis or acute rheumatic fever. Images

Bergey, E J; Stinson, M W

1988-01-01

151

Isolation and immunochemical characterization of carbohydrate antigens prepared from group A Streptococcus pyogenes.  

PubMed

Group A carbohydrate antigens were prepared from isolated cell walls or whole cells of Streptococcus pyogenes strain Sv (group A, M type 3). Cell walls were lysate by the enzymatic action of M1 endo-N-acetylmuramidase. The cell wall lysate was concentrated and chromatographed on a Sephadex G-100 column. Two fractions reactive with group A antisera were obtained. These were composed of N-acetylglucosamine, rhamnose, and peptidoglycan components such as glutamic acid, lysine, alanine, N-acetylmuramic acid and N-acetylglucosamine. For comparison, hot TCA extract of the cell walls (TCAgA) or Rantz and Randall extract of the whole cells (RRgA) was purified chromatographically. The latter two also contained rhamnose and glucosamine, and were reactive with group A antisera. The molecular weights of M1gA antigens were larger than those of TCAgA and RRgA. Hapten inhibition study indicated that N-acetylglucosamine was the most potent inhibitor. PMID:6419494

Hamada, S; Okahashi, N; Yamamoto, T; Morisaki, I; Michalek, S M; McGhee, J R

1983-11-01

152

Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes.  

PubMed

Bacteria encounter oxidative stress by exposure to reactive oxygen species (ROS) present in the aerobic environment and during immune responses. In Streptococcus pyogenes, Dpr has been identified as a stress protein conferring resistance to hydrogen peroxide and multiple other stresses. The expression of Dpr is under perR (peroxide stress response regulator) control. However, the exact molecular mechanism of PerR regulation of Dpr is not clear. In this study, a perR deletion mutant was constructed by double cross-over mutagenesis. The profile of Dpr expression, performed by Western blot assay, revealed growth-phase dependency under normal culture conditions. Dpr expression decreased under iron-restricted conditions, whereas iron, zinc, nickel, and hydrogen peroxide induced its expression. The perR mutant does not induce Dpr as well when exposed to environmental signals. PerR binds the promoter region of dpr. Increased iron and hydrogen peroxide concentrations decreased PerR binding to the promoter region of dpr, suggesting that regulation of Dpr by environmental signals is mediated by PerR directly. PMID:19879189

Tsou, Chih-Cheng; Chiang-Ni, Chuan; Lin, Yee-Shin; Chuang, Woei-Jer; Lin, Ming-T; Liu, Ching-Chuan; Wu, Jiunn-Jong

2009-10-29

153

The Crystal Structure of Streptococcus pyogenes Uridine Phosphorylase Reveals a Distinct Subfamily of Nucleoside Phosphorylases†‡  

PubMed Central

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 Ĺ 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 substrate specificity is similar to that of EcUP, while EcUP is about sevenfold more efficient than SpUP. Biochemical studies on active site mutant SpUP showed that mutations of His169 reduced activity, while mutation of Lys162 abolished all activity, suggesting that 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.

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

2011-01-01

154

Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection  

PubMed Central

Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection. Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different signaling pathways leading to IFN-beta production. Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88. Furthermore, IFN-beta production by macrophages was dependent on the endosomal delivery of streptococcal DNA, while in cDCs streptococcal RNA was identified as the IFN-beta inducer. Despite a role of MyD88 in both cell types, the known IFN-inducing TLRs were individually not required for generation of the IFN-beta response. These results demonstrate that the innate immune system employs several strategies to efficiently recognize S. pyogenes, a pathogenic bacterium that succeeded in avoiding recognition by the standard arsenal of TLRs.

Gratz, Nina; Hartweger, Harald; Matt, Ulrich; Kratochvill, Franz; Janos, Marton; Sigel, Stefanie; Drobits, Barbara; Li, Xiao-Dong; Knapp, Sylvia; Kovarik, Pavel

2011-01-01

155

Virulence of two Streptococcus pyogenes strains (types M1 and M3) associated with toxic-shock-like syndrome depends on an intact mry-like gene.  

PubMed Central

The major virulence factor of Streptococcus pyogenes, the M protein, is positively regulated at the transcriptional level by mry in the M type 6 strain studied. We show here that in two S. pyogenes strains isolated from cases of toxic-shock-like syndrome, a type M1 strain and a type M3 strain, an mry-like gene is also required for resistance to phagocytosis. Images

Perez-Casal, J F; Dillon, H F; Husmann, L K; Graham, B; Scott, J R

1993-01-01

156

Population Genetics and Linkage Analysis of Loci within the FCT Region of Streptococcus pyogenes? †  

PubMed Central

The FCT regions of Streptococcus pyogenes strains encode a variety of cell wall-anchored surface proteins that bind the extracellular matrix of the human host and/or give rise to pilus-like appendages. Strong linkage is evident between transcription-regulatory loci positioned within the FCT and emm regions and the emm pattern genotype marker for preferred infection of the throat or skin. These findings provide a basis for the hypothesis that FCT region gene products contribute to tissue-specific infection. In an initial series of steps to address this possibility, the FCT regions of 13 strains underwent comparative sequence analysis, the gene content of the FCT region was characterized for 113 strains via PCR, and genetic linkage was assessed. A history of extensive recombination within FCT regions was evident. The emm pattern D-defined skin specialist strains were highly homogenous in their FCT region gene contents, whereas the emm pattern A-C-defined throat specialist strains displayed a greater variety of forms. Most pattern A-C strains harbored prtF1 (75%) but lacked cpa (75%). In contrast, the majority of emm pattern D strains had cpa (92%) but lacked prtF1 (79%). Models based on FCT and emm region genotypes revealed the most parsimonious pathways of evolution. Using niche-determining candidate genes to infer phylogeny, emm pattern E strains—the so-called generalists, which lack a strong tissue site preference—occupied a transition zone separating most throat specialists from skin specialists. Overall, population genetic analysis supports the possibility that the FCT region gives rise to surface proteins that are largely necessary, but not always sufficient, to confer tissue site preference for infection.

Kratovac, Zerina; Manoharan, Anand; Luo, Feng; Lizano, Sergio; Bessen, Debra E.

2007-01-01

157

Population genetics and linkage analysis of loci within the FCT region of Streptococcus pyogenes.  

PubMed

The FCT regions of Streptococcus pyogenes strains encode a variety of cell wall-anchored surface proteins that bind the extracellular matrix of the human host and/or give rise to pilus-like appendages. Strong linkage is evident between transcription-regulatory loci positioned within the FCT and emm regions and the emm pattern genotype marker for preferred infection of the throat or skin. These findings provide a basis for the hypothesis that FCT region gene products contribute to tissue-specific infection. In an initial series of steps to address this possibility, the FCT regions of 13 strains underwent comparative sequence analysis, the gene content of the FCT region was characterized for 113 strains via PCR, and genetic linkage was assessed. A history of extensive recombination within FCT regions was evident. The emm pattern D-defined skin specialist strains were highly homogenous in their FCT region gene contents, whereas the emm pattern A-C-defined throat specialist strains displayed a greater variety of forms. Most pattern A-C strains harbored prtF1 (75%) but lacked cpa (75%). In contrast, the majority of emm pattern D strains had cpa (92%) but lacked prtF1 (79%). Models based on FCT and emm region genotypes revealed the most parsimonious pathways of evolution. Using niche-determining candidate genes to infer phylogeny, emm pattern E strains--the so-called generalists, which lack a strong tissue site preference--occupied a transition zone separating most throat specialists from skin specialists. Overall, population genetic analysis supports the possibility that the FCT region gives rise to surface proteins that are largely necessary, but not always sufficient, to confer tissue site preference for infection. PMID:17028269

Kratovac, Zerina; Manoharan, Anand; Luo, Feng; Lizano, Sergio; Bessen, Debra E

2006-10-06

158

Adaptive Evolution of the Streptococcus pyogenes Regulatory Aldolase LacD.1  

PubMed Central

In the human-pathogenic bacterium Streptococcus pyogenes, the tagatose bisphosphate aldolase LacD.1 likely originated through a gene duplication event and was adapted to a role as a metabolic sensor for regulation of virulence gene transcription. Although LacD.1 retains enzymatic activity, its ancestral metabolic function resides in the LacD.2 aldolase, which is required for the catabolism of galactose. In this study, we compared these paralogous proteins to identify characteristics correlated with divergence and novel function. Surprisingly, despite the fact that these proteins have identical active sites and 82% similarity in amino acid sequence, LacD.1 was less efficient at cleaving both fructose and tagatose bisphosphates. Analysis of kinetic properties revealed that LacD.1's adaptation was associated with a decrease in kcat and an increase in Km. Construction and analysis of enzyme chimeras indicated that non-active-site residues previously associated with the variable activities of human aldolase isoenzymes modulated LacD.1's affinity for substrate. Mutant LacD.1 proteins engineered to have LacD.2-like levels of enzymatic efficiency lost the ability to function as regulators, suggesting that an alteration in efficiency was required for adaptation. In competition under growth conditions that mimic a deep-tissue environment, LacD.1 conferred a significant gain in fitness that was associated with its regulatory activity. Taken together, these data suggest that LacD.1's adaptation represents a form of neofunctionalization in which duplication facilitated the gain of regulatory function important for growth in tissue and pathogenesis.

Cusumano, Zachary

2013-01-01

159

Chemokines are secreted by monocytes following OK-432 (lyophilized Streptococcus pyogenes) stimulation  

PubMed Central

Background OK-432, penicillin-killed Streptococcus pyogenes, is used in treating lymphangiomas and carcinomas. We have studied in vitro the role of mononuclear phagocytes (MNPs), including purified monocytes (MOs), in the immune response to OK-432. MIP-1?/? and MCP-1 secretions were assessed in whole blood (WB), peripheral blood mononuclear cells (PBMCs) and purified MOs, after in vitro stimulation with OK-432 with or without adherence for 24 hours. Results OK-432 stimulated MNPs to secrete MCP-1 and MIP-1?/? in healthy individuals and in head and neck squamous cell carcinoma (HNSCC) patients, except for OK-432 stimulation of WB giving a minimal MIP-1?/? response. Upon culture on low-attachment wells, a spontaneous chemokine secretion was observed, with an unchanged secretion following OK-432 stimulation. Inhibition of Syk kinase and/or PI-3 kinase did not significantly change the chemokine response to OK-432, except for MIP-1? production being increased upon Syk inhibitor addition and an increased MCP-1 response upon addition of both inhibitors. Adhesion may possibly involve ?1 and/or ?3 integrins, not ?2, whereas ?1–3 integrins may act as co-stimulatory receptors for OK-432. Based on direct blockage of CD36 or CD18 by antibodies, MCP-1 production may be mediated by CD18 while MIP-1? and MCP-1 production may occur upon binding to CD36. Conclusion Adherent human MOs produce MCP-1 and MIP-1?/? upon stimulation with OK-432. CD36 modulates MIP-1? and MCP-1 response. Thus, to some extent OK-432 acts as a substance whereby only MOs adhered to surfaces secrete MCP-1 and MIP-1?/?, in part explaining why OK-432 is suited as a biological response modifying drug.

Olsnes, Carla; Stavang, Helen; Brokstad, Karl; Olofsson, Jan; Aarstad, Hans J

2009-01-01

160

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

PubMed Central

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.

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

2012-01-01

161

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

SciTech Connect

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.

Tran, Timothy H.; Christoffersen, S.; Allan, Paula W.; Parker, William B.; Piskur, Jure; Serra, I.; Terreni, M.; Ealick, Steven E. (Cornell); (Pavia); (Lund); (Southern Research)

2011-09-20

162

Differences in the epidemiology between paediatric and adult invasive Streptococcus pyogenes infections.  

PubMed

SUMMARY In order to investigate for possible differences between paediatric and adult invasive Streptococcus pyogenes (iGAS) infections, a total of 142 cases were identified in 17 Greek hospitals during 2003-2007, of which 96 were children and 46 adults. Bacteraemia, soft tissue infections, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis were the main clinical presentations (67·6%, 45·1%, 13·4%, and 12·0% of cases, respectively). Bacteraemia and lymphadenitis were significantly more frequent in children (P = 0·019 and 0·021, respectively), whereas STSS was more frequent in adults (P = 0·017). The main predisposing factors in children were varicella and streptococcal pharyngotonsillitis (25% and 19·8%, respectively), as opposed to malignancy, intravenous drug abuse and diabetes mellitus in adults (19·6%, 15·2% and 10·9%, respectively). Of the two dominant emm-types, 1 and 12 (28·2% and 8·5%, respectively), the proportion of emm-type 12 remained stable during the study period, whereas emm-type 1 rates fluctuated considerably. Strains of emm-type 1 from children were associated with erythromycin susceptibility, STSS and intensive-care-unit admission, whereas emm-type 12 isolates from adults were associated with erythromycin and clindamycin resistance. Finally, specific emm-types were detected exclusively in adults or in children. In conclusion, several clinical and epidemiological differences were detected, that could prove useful in designing age-focused strategies for prevention and treatment of iGAS infections. PMID:23746128

Zachariadou, L; Stathi, A; Tassios, P T; Pangalis, A; Legakis, N J; Papaparaskevas, J

2013-06-01

163

Streptococcus pyogenes Infection in Mouse Skin Leads to a Time-Dependent Up-Regulation of Protein H Expression  

PubMed Central

Streptococcus pyogenes protein H (sph) is an immunoglobulin-binding protein present in the Mga regulon of certain M1 serotype isolates. Although sph is present in many strains, it is frequently not expressed. In this paper we show that protein H was highly expressed after bacteria were injected into the skin of mice and were recovered from the blood, kidney, or spleen at various times postinfection. The percentage of protein H-positive colonies increased with time, reaching 100% in the spleen and kidney within 24 to 72 h postinfection. The up-regulation of sph expression was also observed in a mga mutant.

Smith, Tara C.; Sledjeski, Darren D.; Boyle, Michael D. P.

2003-01-01

164

EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG  

PubMed Central

Streptococcus pyogenes is an important human pathogen that selectively interacts with proteins involved in the humoral defense system, such as immunoglobulins and complement factors. In this report we show that S.pyogenes has the ability to hydrolyze the chitobiose core of the asparagine-linked glycan on immuno globulin G (IgG) when bacteria are grown in the presence of human plasma. This activity is associated with the secretion of a novel 108 kDa protein denoted EndoS. EndoS has endoglycosidase activity on purified soluble IgG as well as IgG bound to the bacterial surface. EndoS is required for the activity on IgG, as an isogenic EndoS mutant could not hydrolyze the glycan on IgG. In addition, we show that the secreted streptococcal cysteine proteinase SpeB cleaves IgG in the hinge region in a papain-like manner. This is the first example of an endoglycosidase produced by a bacterial pathogen that selectively hydrolyzes human IgG, and reveals a novel mechanism which may contribute to S.pyogenes pathogenesis.

Collin, Mattias; Olsen, Arne

2001-01-01

165

MicroRNA fragments derived from Streptococcus pyogenes enable activation of neutrophil phagocytosis: in vitro study.  

PubMed

MicroRNAs are single-stranded RNAs that regulate gene expression by forming imperfect base pairs, which have also been speculated to play regulatory roles in gene expression of Streptococcus pyogenes itself. We hypothesized that bacterial microRNAs cause molecular interference in host, when there is high homology to human microRNAs. Total RNA from cultured S. pyogenes strain SSI-1 was isolated and the cDNA fragments were then inserted into vector plasmid and transformed to competent cells, after which genomic sequence analyses were performed. Cell transfection, evaluation of mRNA transcription, measurement of inflammatory mediators, and assessment of surviving bacteria with murine splenocytes were also performed. Three microRNAs were selected from about 600 candidates according to their homology with human genome DNA. In the quantitative method, transcription of nasopharyngeal cells with microRNA was significantly lower in 2 of 11 targets, and greater in 10 of 11 targets. The ELISA findings revealed that transcription of MIP-2 was significantly greater with miR-SSI1-221 and miR-SSI1-281. Furthermore, strain SSI-1 had significantly higher survival in the supernatant of the control as compared to the miR-SSI1-221 and miR-SSI1-281 transfected cells. In conclusion, microRNA fragments derived from S. pyogenes have a high homology to the human genome and contribute to enhancement of the host immune system. PMID:23220108

Ogawa, Taiji; Terao, Yutaka; Honda-Ogawa, Mariko; Hashimoto, Sakae; Ikebe, Kazunori; Maeda, Yoshinobu; Kawabata, Shigetada

2012-12-06

166

Recurrent fatal necrotizing fasciitis due to Streptococcus pyogenes in a child with hereditary sensory and automic neuropathy type IV.  

PubMed

Although necrotizing fasciitis (NF) is a rapidly progressive infection, recurrent NF is very rare. Herein we report a rare case of recurrent NF due to Streptococcus pyogenes. A 12-year-old female with hereditary sensory and autonomic neuropathy (HSAN) type IV presented with fever and swelling on her left knee. NF was diagnosed and she was treated successfully. Two years later she was readmitted with NF of the right knee and limb. Despite treatment, progressive tissue necrosis developed and proximal femur amputation was performed. Eight months following the second attack she was readmitted with NF of her left knee and her entire leg. Despite a wide surgical debridement and antibiotic treatment, the clinical status of the patient failed to improve and she subsequently died. Although many conditions have been reported to be predisposing factors for NF, this is the first report of an association between HSAN type IV and recurrent NF due to S. pyogenes. We recommend antibiotic prophylaxis for patients with NF due to S. pyogenes, especially for those with predisposing factors. PMID:21519130

Kuzdan, Canan; Soysal, Ahmet; Altinkanat, Gül?en; Aksu, Burak; Söyletir, Güner; Bakir, Mustafa

2011-01-01

167

EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG.  

PubMed

Streptococcus pyogenes is an important human pathogen that selectively interacts with proteins involved in the humoral defense system, such as immunoglobulins and complement factors. In this report we show that S.pyogenes has the ability to hydrolyze the chitobiose core of the asparagine-linked glycan on immuno globulin G (IgG) when bacteria are grown in the presence of human plasma. This activity is associated with the secretion of a novel 108 kDa protein denoted EndoS. EndoS has endoglycosidase activity on purified soluble IgG as well as IgG bound to the bacterial surface. EndoS is required for the activity on IgG, as an isogenic EndoS mutant could not hydrolyze the glycan on IgG. In addition, we show that the secreted streptococcal cysteine proteinase SpeB cleaves IgG in the hinge region in a papain-like manner. This is the first example of an endoglycosidase produced by a bacterial pathogen that selectively hydrolyzes human IgG, and reveals a novel mechanism which may contribute to S.pyogenes pathogenesis. PMID:11406581

Collin, M; Olsén, A

2001-06-15

168

Prevalence and Clonal Characterization of Streptococcus pyogenes Clinical Isolates with Reduced Fluoroquinolone Susceptibility in Spain ?  

PubMed Central

The aim of this study was to determine the prevalence and characteristics of non-fluoroquinolone (FQ)-susceptible Streptococcus pyogenes isolates and to study their mechanisms of resistance. We performed a prospective prevalence study with 468 isolates collected from 2005 to 2007 and a retrospective study that was based on the examination of existing data collected from 1999 to 2008. The retrospective study included data for isolates with high-level resistance (HR) to ciprofloxacin (MIC ? 32 ?g/ml) (HR isolates) and isolates with the same emm types as those reported in the literature with low-level resistance (LR) to ciprofloxacin (MICs, 2 to 8 ?g/ml) (LR isolates, n = 205). Genetic characterization of the isolates was performed by means of emm typing and multilocus sequence typing. The prevalence of LR ranged from 1.9% in 2005 to 30.8% in 2007. This increase was mainly due to the circulation of an emm6 subtype (emm6.4) that represented 77.1% of the LR isolates in 2007. Notably, another emm6 subtype, also detected in 2007 (emm6.37), showed coresistance to 14- and 15-membered macrolides mediated by the mefA gene. Only three HR isolates were detected (isolates emm68.1/ST247/T3,13,B3264, emm77/ST399/T28, and emm28/ST52/T28), and all were identified in the retrospective study. Overall, the 673 isolates represented 25 emm types. All LR isolates were clustered into two emm types: emm6 (six emm6 subtypes) and emm75. All the 156 emm6 isolates had LR, harbored the Ser79/Ala mutation in the parC gene product, and had the same sequence type (ST), ST382. Most (21/33) of the emm75 isolates had LR, showed the Ser79/Phe plus Asp91/Asn double mutation in the parC gene product, and were ST150. The Asp91/Asn mutation by itself did not confer resistance to FQs.

Montes, Milagrosa; Tamayo, Esther; Orden, Beatriz; Larruskain, Julian; Perez-Trallero, Emilio

2010-01-01

169

Prevalence and clonal characterization of Streptococcus pyogenes clinical isolates with reduced fluoroquinolone susceptibility in Spain.  

PubMed

The aim of this study was to determine the prevalence and characteristics of non-fluoroquinolone (FQ)-susceptible Streptococcus pyogenes isolates and to study their mechanisms of resistance. We performed a prospective prevalence study with 468 isolates collected from 2005 to 2007 and a retrospective study that was based on the examination of existing data collected from 1999 to 2008. The retrospective study included data for isolates with high-level resistance (HR) to ciprofloxacin (MIC >or= 32 microg/ml) (HR isolates) and isolates with the same emm types as those reported in the literature with low-level resistance (LR) to ciprofloxacin (MICs, 2 to 8 microg/ml) (LR isolates, n = 205). Genetic characterization of the isolates was performed by means of emm typing and multilocus sequence typing. The prevalence of LR ranged from 1.9% in 2005 to 30.8% in 2007. This increase was mainly due to the circulation of an emm6 subtype (emm6.4) that represented 77.1% of the LR isolates in 2007. Notably, another emm6 subtype, also detected in 2007 (emm6.37), showed coresistance to 14- and 15-membered macrolides mediated by the mefA gene. Only three HR isolates were detected (isolates emm68.1/ST247/T3,13,B3264, emm77/ST399/T28, and emm28/ST52/T28), and all were identified in the retrospective study. Overall, the 673 isolates represented 25 emm types. All LR isolates were clustered into two emm types: emm6 (six emm6 subtypes) and emm75. All the 156 emm6 isolates had LR, harbored the Ser79/Ala mutation in the parC gene product, and had the same sequence type (ST), ST382. Most (21/33) of the emm75 isolates had LR, showed the Ser79/Phe plus Asp91/Asn double mutation in the parC gene product, and were ST150. The Asp91/Asn mutation by itself did not confer resistance to FQs. PMID:19805559

Montes, Milagrosa; Tamayo, Esther; Orden, Beatriz; Larruskain, Julián; Perez-Trallero, Emilio

2009-10-05

170

tRNA Modification by GidA\\/MnmE Is Necessary for Streptococcus pyogenes Virulence: a New Strategy To Make Live Attenuated Strains  

Microsoft Academic Search

Studies directed at vaccine development and mucosal immunity against Streptococcus pyogenes would benefit from the availability of live attenuated strains. Our approach for production of candidate live attenuated strains was to identify mutations that did not alter growth in vitro and did not alter the overall complement of virulence factors produced but did result in reduced levels of expression of

Kyu Hong Cho; Michael G. Caparon

2008-01-01

171

Activity of Retapamulin against Streptococcus pyogenes and Staphylococcus aureus Evaluated by Agar Dilution, Microdilution, E-Test, and Disk Diffusion Methodologies  

Microsoft Academic Search

The in vitro activity of retapamulin against 106 Staphylococcus aureus isolates and 109 Streptococcus pyogenes isolates was evaluated by the agar dilution, broth microdilution, E-test, and disk diffusion methodologies. Where possible, the tests were performed by using the CLSI methodology. The results of agar dilution, broth microdilution, and E-test (all with incubation in ambient air) for S. aureus yielded similar

Glenn A. Pankuch; Gengrong Lin; Dianne B. Hoellman; Caryn E. Good; Michael R. Jacobs; Peter C. Appelbaum

2006-01-01

172

Impact of the SpeB Protease on Binding of the Complement Regulatory Proteins Factor H and Factor H-Like Protein 1 by Streptococcus pyogenes  

Microsoft Academic Search

Microbial pathogens often exploit human complement regulatory proteins such as factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an FH and FHL-1 binding protein expressed on the sur- face of the human pathogenic bacterium Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft- tissue infections. Fba has been shown to contribute to phagocytosis

Lin Wei; Vinod Pandiripally; Eugene Gregory; Micaya Clymer; David Cue

2005-01-01

173

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

Microsoft Academic Search

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

Kishore Viswanathan; Kathleen M. Frey; Eric W. Scocchera; Brooke D. Martin; P. Whitney Swain III; Jeremy B. Alverson; Nigel D. Priestley; Amy C. Anderson; Dennis L. Wright

2012-01-01

174

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

PubMed Central

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 naďve 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.

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

2009-01-01

175

Crystal structures of Streptococcus pyogenes Dpr reveal a dodecameric iron-binding protein with a ferroxidase site.  

PubMed

DNA-binding protein from starved cells (Dps)-like proteins are key factors involved in oxidative stress protection in bacteria. They bind and oxidize iron, thus preventing the formation of harmful reactive oxygen species that can damage biomolecules, particularly DNA. Dps-like proteins are composed of 12 identical subunits assembled in a spherical structure with a hollow central cavity. The iron oxidation occurs at 12 intersubunit sites located at dimer interfaces. Streptococcus pyogenes Dps-like peroxide resistance protein (Dpr) has been previously found to protect the catalase-lacking S. pyogenes bacterium from oxidative stress. We have determined the crystal structure of S. pyogenes Dpr, the second Dpr structure from a streptococcal bacterium, in iron-free and iron-bound forms at 2.0- and 1.93-A resolution, respectively. The iron binds to well-conserved sites at dimer interfaces and is coordinated directly to Asp77 and Glu81 from one monomer, His50 from a twofold symmetry-related monomer, a glycerol molecule, and a water molecule. Upon iron binding, Asp77 and Glu81 change conformation. Site-directed mutagenesis of active-site residues His50, His62, Asp66, Asp77, and Glu81 to Ala revealed a dramatic decrease in iron incorporation. A short helix at the N-terminal was found in a different position compared with other Dps-like proteins. Two types of pores were identified in the dodecamer. Although the N-terminal pore was found to be similar to that of other Dps-like proteins, the C-terminal pore was found to be blocked by bulky Tyr residues instead of small residues present in other Dps-like proteins. PMID:19727858

Haikarainen, Teemu; Tsou, Chih-Cheng; Wu, Jiunn-Jong; Papageorgiou, Anastassios C

2009-09-02

176

Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their ?-domains.  

PubMed

Cluster 1 streptokinases (SK1) from Streptococcus pyogenes (GAS) show substantially higher human plasminogen (hPg) activation activities and tighter hPg binding affinities than cluster 2b streptokinases (SK2b) in solution. The extent to which the different domains of SK are responsible for these differences is unknown. We exchanged each of the three known SK domains (?, ?, and ?) between SK1 and SK2b and assessed the function of the resulting variants. Our results show that primary structural differences in the ?-domains dictate these functional differences. This first report on the primary structure-functional relationship between naturally occurring SK1 and SK2b sheds new light on the mechanism of hPg activation by SK, a critical virulence determinant in this species of human pathogenic bacteria. PMID:23474243

Zhang, Yueling; Liang, Zhong; Glinton, Kristofor; Ploplis, Victoria A; Castellino, Francis J

2013-03-07

177

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

PubMed Central

The tRNA-specific adenosine deaminase from the pathogenic bacteria Streptococcus pyogenes (spTAD) has been overexpressed in Escherichia coli and crystallized in the presence of Zn2+ ion at 295?K using ammonium sulfate as a precipitant. Flash-cooled crystals of spTAD diffracted to 2.0?Ĺ using 30%(v/v) glycerol as a cryoprotectant. X-ray diffraction data have been collected to 2.0?Ĺ using synchrotron radiation. The crystal belongs to the tetragonal space group P42212, with unit-cell parameters a = b = 81.042, c = 81.270?Ĺ. The asymmetric unit contains one subunit of spTAD, with a corresponding crystal volume per protein weight (V M) of 3.3?Ĺ3?Da?1 and a solvent content of 62.7%.

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

2005-01-01

178

Illustration of a Common Framework for Relating Multiple Typing Methods by Application to Macrolide-Resistant Streptococcus pyogenes  

PubMed Central

The studies that correlate the results obtained by different typing methodologies rely solely on qualitative comparisons of the groups defined by each methodology. We propose a framework of measures for the quantitative assessment of correspondences between different typing methods as a first step to the global mapping of type equivalences. A collection of 325 macrolide-resistant Streptococcus pyogenes isolates associated with pharyngitis cases in Portugal was used to benchmark the proposed measures. All isolates were characterized by macrolide resistance phenotyping, T serotyping, emm sequence typing, and pulsed-field gel electrophoresis (PFGE), using SmaI or Cfr9I and SfiI. A subset of 41 isolates, representing each PFGE cluster, was also characterized by multilocus sequence typing (MLST). The application of Adjusted Rand and Wallace indices allowed the evaluation of the strength and the directionality of the correspondences between the various typing methods and showed that if PFGE or MLST data are available one can confidently predict the emm type (Wallace coefficients of 0.952 for both methods). In contrast, emm typing was a poor predictor of PFGE cluster or MLST sequence type (Wallace coefficients of 0.803 and 0.655, respectively). This was confirmed by the analysis of the larger data set available from http://spyogenes.mlst.net and underscores the necessity of performing PFGE or MLST to unambiguously define clones in S. pyogenes.

Carrico, J. A.; Silva-Costa, C.; Melo-Cristino, J.; Pinto, F. R.; de Lencastre, H.; Almeida, J. S.; Ramirez, M.

2006-01-01

179

Illustration of a common framework for relating multiple typing methods by application to macrolide-resistant Streptococcus pyogenes.  

PubMed

The studies that correlate the results obtained by different typing methodologies rely solely on qualitative comparisons of the groups defined by each methodology. We propose a framework of measures for the quantitative assessment of correspondences between different typing methods as a first step to the global mapping of type equivalences. A collection of 325 macrolide-resistant Streptococcus pyogenes isolates associated with pharyngitis cases in Portugal was used to benchmark the proposed measures. All isolates were characterized by macrolide resistance phenotyping, T serotyping, emm sequence typing, and pulsed-field gel electrophoresis (PFGE), using SmaI or Cfr9I and SfiI. A subset of 41 isolates, representing each PFGE cluster, was also characterized by multilocus sequence typing (MLST). The application of Adjusted Rand and Wallace indices allowed the evaluation of the strength and the directionality of the correspondences between the various typing methods and showed that if PFGE or MLST data are available one can confidently predict the emm type (Wallace coefficients of 0.952 for both methods). In contrast, emm typing was a poor predictor of PFGE cluster or MLST sequence type (Wallace coefficients of 0.803 and 0.655, respectively). This was confirmed by the analysis of the larger data set available from http://spyogenes.mlst.net and underscores the necessity of performing PFGE or MLST to unambiguously define clones in S. pyogenes. PMID:16825375

Carriço, J A; Silva-Costa, C; Melo-Cristino, J; Pinto, F R; de Lencastre, H; Almeida, J S; Ramirez, M

2006-07-01

180

Streptococcus pyogenes SpyCEP Influences Host-Pathogen Interactions during Infection in a Murine Air Pouch Model  

PubMed Central

Streptococcus pyogenes is a major human pathogen worldwide, responsible for both local and systemic infections. These bacteria express the subtilisin-like protease SpyCEP which cleaves human IL-8 and related chemokines. We show that localization of SpyCEP is growth-phase and strain dependent. Significant shedding was observed only in a strain naturally overexpressing SpyCEP, and shedding was not dependent on SpyCEP autoproteolytic activity. Surface-bound SpyCEP in two different strains was capable of cleaving IL-8. To investigate SpyCEP action in vivo, we adapted the mouse air pouch model of infection for parallel quantification of bacterial growth, host immune cell recruitment and chemokine levels in situ. In response to infection, the predominant cells recruited were neutrophils, monocytes and eosinophils. Concomitantly, the chemokines KC, LIX, and MIP-2 in situ were drastically increased in mice infected with the SpyCEP knockout strain, and growth of this mutant strain was reduced compared to the wild type. SpyCEP has been described as a potential vaccine candidate against S. pyogenes, and we showed that surface-associated SpyCEP was recognized by specific antibodies. In vitro, such antibodies also counteracted the inhibitory effects of SpyCEP on chemokine mediated PMN recruitment. Thus, ?-SpyCEP antibodies may benefit the host both directly by enabling opsonophagocytosis, and indirectly, by neutralizing an important virulence factor. The animal model we employed shows promise for broad application in the study of bacterial pathogenesis.

Chiappini, Nico; Seubert, Anja; Telford, John L.; Grandi, Guido; Serruto, Davide; Margarit, Immaculada; Janulczyk, Robert

2012-01-01

181

Streptococcus pyogenes pharyngitis: characterization of strains by multilocus enzyme genotype, M and T protein serotype, and pyrogenic exotoxin gene probing.  

PubMed Central

Multilocus enzyme electrophoresis, serological characterization of M and T proteins, and probing for pyrogenic exotoxin A and C genes were used to investigate the bacteriologic epidemiology of strains of Streptococcus pyogenes recovered primarily from patients with recurrent pharyngitis. A total of 164 strains recovered from individuals living in nine states of the United States was analyzed. Two-thirds of the patients in our sample were infected with the homologous strain following antibiotic therapy and presumably represented treatment failures, whereas the other one-third of the patients were infected with a heterologous strain after therapy and probably represented reinfections. Multilocus enzyme electrophoresis was as efficacious in strain discrimination as serologic typing techniques were and, in addition, successfully characterized all organisms that were serologically nontypeable. Two clones of S. pyogenes responsible for most of the episodes of toxic shock-like syndrome in the United States are geographically widespread, but they vary by locality in the frequency of their occurrence. Compared with a sample of strains cultured from patients whose pharyngeal infections were eliminated by antimicrobial therapy, these two clones were statistically overrepresented among organisms that cause recurrent pharyngitis.

Musser, J M; Gray, B M; Schlievert, P M; Pichichero, M E

1992-01-01

182

Activities of a New Fluoroketolide, HMR 3787, and Its (Des)-Fluor Derivative RU 64399 Compared to Those of Telithromycin, Erythromycin A, Azithromycin, Clarithromycin, and Clindamycin against Macrolide-Susceptible or -Resistant Streptococcus pneumoniae and S. pyogenes  

PubMed Central

Activities of HMR 3787 and RU 64399 were compared to those of three macrolides, telithromycin, and clindamycin against 175 Streptococcus pneumoniae isolates and 121 Streptococcus pyogenes isolates. HMR3787 and telithromycin were the most active compounds tested against pneumococci. Telithromycin and RU 64399 were equally active against macrolide-susceptible (MICs, 0.008 to 0.06 ?g/ml) and -resistant S. pyogenes isolates, but HMR 3787 had lower MICs for ermB strains.

Nagai, Kensuke; Davies, Todd A.; Ednie, Lois M.; Bryskier, Andre; Palavecino, Elizabeth; Jacobs, Michael R.; Appelbaum, Peter C.

2001-01-01

183

Mutational loss of sensitivity to mutacin GS-5 in Streptococcus pyogenes: characterization of a mutant deficient in receptor protein.  

PubMed Central

By means of a stepwise selection procedure, mutants capable of growing in the presence of relatively high multiplicities of a bacteriocin from Streptococcus mutans GS-5 were obtained from a sensitivie strain of Streptococcus pyogenes. Mutacin-neutralizing activity of cell extracts containing receptor protein was examined in one variant that adsorbed 1/6 the amount of bacteriocin adsorbed by the parent strain under conditions equivalent to "saturation." Partially purified receptor protein from both parent and mutant cells neutralized an equivalent amount of bacteriocin on a weight-to-weight basis, indicating that in vitro there was no significant difference in affinity for the mutacin between the respective receptor fractions. Cell extracts from the mutant, solubilized by treatment with trichloroacetic acid, neither neutralized mutacin activity nor interfered with receptor protein-mediated mutacin neutralization in vitro. The mutant phenotype may thus represent a cell surface density of receptor protein which results in the adsorption of sublethal amounts of mutacin. The mutant retained its sensitivity to other mutacins, e.g., those produced by strains LM-7 and BHT of S. mutans, and did not differ from wild-type cells with respect to either detergent sensitivity (sodium lauryl sulfate and Triton X-100) or to inhibition by penicillin, rifampin, bacitracin, erythromycin, and tetracycline.

Franker, C K

1980-01-01

184

Effects of the ERES Pathogenicity Region Regulator Ralp3 on Streptococcus pyogenes Serotype M49 Virulence Factor Expression  

PubMed Central

Streptococcus pyogenes (group A streptococcus [GAS]) is a highly virulent Gram-positive bacterium. For successful infection, GAS expresses many virulence factors, which are clustered together with transcriptional regulators in distinct genomic regions. Ralp3 is a central regulator of the ERES region. In this study, we investigated the role of Ralp3 in GAS M49 pathogenesis. The inactivation of Ralp3 resulted in reduced attachment to and internalization into human keratinocytes. The ?ralp3 mutant failed to survive in human blood and serum, and the hyaluronic acid capsule was slightly decreased. In addition, the mutant showed a lower binding capacity to human plasminogen, and the SpeB activity was significantly decreased. Complementation of the ?ralp3 mutant restored the wild-type phenotype. The transcriptome and quantitative reverse transcription-PCR analysis of the serotype M49 GAS strain and its isogenic ?ralp3 mutant identified 16 genes as upregulated, and 43 genes were found to be downregulated. Among the downregulated genes, there were open reading frames encoding proteins involved in metabolism (e.g., both lac operons and the fru operon), genes encoding lantibiotics (e.g., the putative salivaricin operon), and ORFs encoding virulence factors (such as the whole Mga core regulon and further genes under Mga control). In summary, the ERES region regulator Ralp3 is an important serotype-specific transcriptional regulator for virulence and metabolic control.

Siemens, Nikolai; Fiedler, Tomas; Normann, Jana; Klein, Johannes; Munch, Richard; Patenge, Nadja

2012-01-01

185

Localization by site-directed mutagenesis of the site in human complement factor H that binds to Streptococcus pyogenes M protein.  

PubMed Central

M-protein receptors located on Streptococcus pyogenes cells are known to bind human plasma protein factor H. Human factor H is composed of 20 short consensus repeat (SCR) domains containing approximately 60 amino acids each. Factor H controls the activation of the alternative pathway of complement in plasma. We have scanned the entire human factor H molecule by site-directed deletion mutagenesis, expressed the recombinant proteins in insect cells using the baculovirus system, and measured the binding of different purified mutant proteins to three strains of S. pyogenes. These studies have revealed that recombinant factor H lacking SCR domains 6 to 10 does not bind to wild-type M+ S. pyogenes JRS4. Experiments performed with S. pyogenes JRS251, in which both C-repeat domains of M protein were deleted, demonstrated that all of the factor H mutant proteins bound weakly to these cells except those lacking the SCR region from domains 6 to 10. Neither human factor H nor any of the recombinant proteins bound to the M- strain JRS145. Our results indicate that the only binding site on human factor H that interacts with streptococcus M protein is located in SCR domains 6 to 10 of factor H and that regions of M protein outside the C-repeat domains are involved in binding factor H.

Sharma, A K; Pangburn, M K

1997-01-01

186

Different Forms of Streptolysin O Produced byStreptococcus pyogenes and byEscherichia coliExpressing Recombinant Toxin: Cleavage by Streptococcal Cysteine Protease  

Microsoft Academic Search

To resolve apparent discrepancies in the literature, N-terminal sequences of the active high- and low- molecular-weight (high- and low-Mr) forms of native streptolysin O (nSLO) purified from Streptococcus pyogenes culture supernatants and of the similar-size high- and low-Mr forms of recombinant SLO (rSLO) found in the periplasm ofEscherichia coliexpressing a clonedslogene were determined. The high-Mrforms of nSLO and rSLO are

MICHAEL PINKNEY; VIVEK KAPUR; JENNY SMITH; U. WELLER; MICHAEL PALMER; MICHAEL GLANVILLE; MARTINA MESSNER; JAMES M. MUSSER

1995-01-01

187

The transcriptional terminator sequences downstream of the covR gene terminate covR\\/S operon transcription to generate covR monocistronic transcripts in Streptococcus pyogenes  

Microsoft Academic Search

CovR\\/S is an important two component regulatory system, which regulates about 15% of the gene expression in Streptococcus pyogenes. The covR\\/S locus was identified as an operon generating an RNA transcript around 2.5-kb in size. In this study, we found the covR\\/S operon produced three RNA transcripts (around 2.5-, 1.0-, and 0.8-kb in size). Using RNA transcriptional terminator sequence prediction

Chuan Chiang-Ni; Chih-Cheng Tsou; Yee-Shin Lin; Woei-Jer Chuang; Ming-T. Lin; Ching-Chuan Liu; Jiunn-Jong Wu

2008-01-01

188

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

PubMed

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

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

2012-03-22

189

RscA, a Member of the MDR1 Family of Transporters, Is Repressed by CovR and Required for Growth of Streptococcus pyogenes under Heat Stress†  

PubMed Central

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°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°C but not at pH 6.0. Thus, for GAS to grow at 40°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.

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

2006-01-01

190

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

PubMed

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

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

2006-01-01

191

Mode of Expression and Functional Characterization of FCT-3 Pilus Region-Encoded Proteins in Streptococcus pyogenes Serotype M49? †  

PubMed Central

The human pathogen Streptococcus pyogenes (group A streptococcus [GAS]) pilus components, suggested to play a role in pathogenesis, are encoded in the variable FCT (fibronectin- and collagen-binding T-antigen) region. We investigated the functions of sortase A (SrtA), sortase C2 (SrtC2), and the FctA protein of the most prevalent type 3 FCT region from a serotype M49 strain. Although it is considered a housekeeping sortase, SrtA's activity is involved in pilus formation in addition to its essentiality for GAS extracellular matrix protein binding, host cell adherence/internalization, survival in human blood, and biofilm formation. SrtC2 activity is crucial for pilus formation but dispensable for the other phenotypes tested in vitro. FctA is the major pilus backbone protein, simultaneously acting as the M49 T antigen, and requires SrtC2 and LepA, a signal peptidase I homologue, for monomeric surface expression and polymerization, respectively. Collagen-binding protein Cpa expression supports pilus formation at the pilus base. Immunofluorescence microscopy and fluorescence-activated cell sorting analysis revealed several unexpected expression patterns, as follows: (i) the monomeric pilus protein FctA was found exclusively at the old poles of GAS cells, (ii) FctA protein expression increased with lower temperatures, and (iii) FctA protein expression was restricted to 20 to 50% of a given GAS M49 population, suggesting regulation by a bistability mode. Notably, disruption of pilus assembly by sortase deletion rendered GAS serotype M49 significantly more aggressive in a dermonecrotic mouse infection model, indicating that sortase activity and, consequently, pilus expression allow a subpopulation of this GAS serotype to be less aggressive. Thus, pilus expression may not be a virulence attribute of GAS per se.

Nakata, Masanobu; Koller, Thomas; Moritz, Karin; Ribardo, Deborah; Jonas, Ludwig; McIver, Kevin S.; Sumitomo, Tomoko; Terao, Yutaka; Kawabata, Shigetada; Podbielski, Andreas; Kreikemeyer, Bernd

2009-01-01

192

Generation and Surface Localization of Intact M Protein in Streptococcus pyogenes Are Dependent on sagA  

PubMed Central

The M protein is an important surface-located virulence factor of Streptococcus pyogenes, the group A streptococcus (GAS). Expression of M protein is primarily controlled by Mga, a transcriptional activator protein. A recent report suggested that the sag locus, which includes nine genes necessary and sufficient for production of streptolysin S, another GAS virulence factor, is also needed for transcription of emm, encoding the M protein (Z. Li, D. D. Sledjeski, B. Kreikemeyer, A. Podbielski, and M. D. Boyle, J. Bacteriol. 181:6019–6027, 1999). To investigate this in more detail, we constructed an insertion-deletion mutation in sagA, the first gene in the sag locus, in the M6 strain JRS4. The resulting strain, JRS470, produced no detectable streptolysin S and showed a drastic reduction in cell surface-associated M protein, as measured by cell aggregation and Western blot analysis. However, transcription of the emm gene was unaffected by the sagA mutation. Detailed analysis with monoclonal antibodies and an antipeptide antibody showed that the M protein in the sagA mutant strain was truncated so that it lacks the C-repeat region and the C-terminal domain required for anchoring it to the cell surface. This truncated M protein was largely found, as expected, in the culture supernatant. Lack of surface-located M protein made the sagA mutant strain susceptible to phagocytosis. Thus, although sagA does not affect transcription of the M6 protein gene, it is needed for the surface localization of this important virulence factor.

Biswas, Indranil; Germon, Pierre; McDade, Kathleen; Scott, June R.

2001-01-01

193

A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft-tissue infection induced by Streptococcus pyogenes.  

PubMed

Staphylococcus aureus and group A Streptococcus pyogenes (GAS) express superantigen (SAg) exotoxin proteins capable of inducing lethal shock. To induce toxicity, SAgs must bind not only to the major histocompatibility complex II molecule of antigen-presenting cells and the variable ? chain of the T-cell receptor but also to the dimer interface of the T-cell costimulatory receptor CD28. Here, we show that the CD28-mimetic peptide AB103 (originally designated "p2TA") protects mice from lethal challenge with streptococcal exotoxin A, as well as from lethal GAS bacterial infection in a murine model of necrotizing soft-tissue infection. Administration of a single dose of AB103 increased survival when given up to 5 hours after infection, reduced inflammatory cytokine expression and bacterial burden at the site of infection, and improved muscle inflammation in a dose-dependent manner, without compromising cellular and humoral immunity. Thus, AB103 merits further investigation as a potential therapeutic in SAg-mediated necrotizing soft-tissue infection. PMID:23493729

Ramachandran, Girish; Tulapurkar, Mohan E; Harris, Kristina M; Arad, Gila; Shirvan, Anat; Shemesh, Ronen; Detolla, Louis J; Benazzi, Cinzia; Opal, Steven M; Kaempfer, Raymond; Cross, Alan S

2013-03-14

194

Characterisation of the main clones of Streptococcus pyogenes carrying the ermA (subclass TR) gene in Spain.  

PubMed

Seventy-four Streptococcus pyogenes isolates showing the macrolide-lincosamide-streptogramin B (MLS(B)) resistance phenotype carrying the ermA gene (72 of which showed the inducible resistance phenotype) were obtained between 1999 and 2004. Seven different sequence types (STs) and emm types were detected: emm22/ST46 (n=33); emm77/ST63 (n=22); emm73/ST331 (n=10); emm94/ST89 (n=6); and one isolate each of emm28/ST52, emm11/ST403 and emm4/ST38. All ST46 isolates were susceptible to tetracycline and almost all reacted against the T12 type (all agglutinated into the T-pattern 3/12/13/B3264). Resistance to tetracycline was observed in all ST63 (tetO+) and ST89 (tetM+) isolates. Most of the ST63 isolates reacted against the T28 type (all agglutinated into the T-pattern 9/13/28). The 74 isolates were grouped into eight pulsed-field gel electrophoresis pulsotypes (one cluster for each emm/ST type, except for emm77/ST63). PMID:17000084

Montes, Milagrosa; Orden, Beatriz; Tamayo, Esther; Alos, Juan-Ignacio; Pérez-Trallero, Emilio

2006-09-26

195

[Resistance to macrolides in the species Streptococcus pyogenes in the Czech Republic in 1996-2003].  

PubMed

The study of the prevalence of erythromycin resistance in 22 169 S. pyogenes strains in the Czech Republic in 1996-2003 on the background of rough data on the nationwide consumption of macrolide antibiotics confirmed that the exponential growth of resistance observed in 1998-2001 copied with a delay the rise in macrolide antibiotic consumption recorded in 1992-1995. The highest frequency of erythromycin resistance was found in 2001 (16.5%) with a subsequent decrease to 14.5% in 2002 and to 9.1% in 2003. The drop in resistance followed the stagnation in macrolide consumption and its decrease by 17% in 2002. Upward and downward trends in macrolide resistance in different regions and age groups copied the nationwide trends with some quantitative differences that could not be analyzed in view of the lack of detailed data on antibiotic consumption. A 99.5% concordance was found between the results of the phenotypic method and those of detection of genes coding for constitutive, inducible and efflux resistance to macrolide-lincosamide-streptograminB (MLSB) antibiotics. In 2001 when the highest erythromycin resistance was recorded in the Czech Republic, most of the tested strains (91.2%) showed resistance to all MLSB antibiotics, with macrolide efflux (susceptibility to lincosamides and 16-membered macrolides was conserved) being implicated in resistance of 8.8% of the strains only. In 2003, the number of erythromycin resistant strains decreased and the resistance mechanism was ascribed to macrolide efflux in 26.8% of them. Almost all of the strains with constitutive or induced MLSB resistance are also resistant to either tetracycline or bacitracin or both. In the light of S. pyogenes resistance to bacitracin, the bacitracin disk is not usable in preliminary identification any more. PMID:15633541

Urbásková, P; Jakub?, V

2004-11-01

196

Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of SpyCEP, a candidate antigen for a vaccine against Streptococcus pyogenes.  

PubMed

Streptococcus pyogenes (Group A streptococcus; GAS) is an important human pathogen against which an effective vaccine does not yet exist. The S. pyogenes protein SpyCEP (S. pyogenes cell-envelope proteinase) is a surface-exposed subtilisin-like serine protease of 1647 amino acids. In addition to its auto-protease activity, SpyCEP is capable of cleaving interleukin 8 and related chemokines, contributing to GAS immune-evasion strategies. SpyCEP is immunogenic and confers protection in animal models of GAS infections. In order to structurally characterize this promising vaccine candidate, several SpyCEP protein-expression constructs were designed, cloned, produced in Escherichia coli, purified by affinity chromatography and subjected to crystallization trials. Crystals of a selenomethionyl form of a near-full-length SpyCEP ectodomain were obtained. The crystals diffracted X-rays to 3.3?Ĺ resolution and belonged to space group C2, with unit-cell parameters a = 139.2, b = 120.4, c = 104.3?Ĺ, ? = 111°. PMID:24100558

Abate, Francesca; Malito, Enrico; Falugi, Fabiana; Margarit Y Ros, Immaculada; Bottomley, Matthew James

2013-09-28

197

Serotype- and strain- dependent contribution of the sensor kinase CovS of the CovRS two-component system to Streptococcus pyogenes pathogenesis  

PubMed Central

Background The Streptococcus pyogenes (group A streptococci, GAS) two-component signal transduction system CovRS has been described to be important for pathogenesis of this exclusively human bacterial species. If this system acts uniquely in all serotypes is currently unclear. Presence of serotype- or strain-dependent regulatory circuits and polarity is an emerging scheme in Streptococcus pyogenes pathogenesis. Thus, the contribution of the sensor kinase (CovS) of the global regulatory two-component signal transduction system CovRS on pathogenesis of several M serotypes was investigated. Results CovS mutation uniformly repressed capsule expression and hampered keratinocyte adherence in all tested serotypes. However, a serotype- and even strain-dependent contribution on survival in whole human blood and biofilm formation was noted, respectively. Conclusions These data provide new information on the action of the CovS sensor kinase and revealed that its activity on capsule expression and keratinocyte adherence is uniform across serotypes, whereas the influence on biofilm formation and blood survival is serotype or even strain dependent. This adds the CovRS system to a growing list of serotype-specific acting regulatory loci in S. pyogenes.

2010-01-01

198

The ancillary protein 1 of Streptococcus pyogenes FCT-1 pili mediates cell adhesion and biofilm formation through heterophilic as well as homophilic interactions  

PubMed Central

Summary Gram-positive pili are known to play a role in bacterial adhesion to epithelial cells and in the formation of biofilm microbial communities. In the present study we undertook the functional characterization of the pilus ancillary protein 1 (AP1_M6) from Streptococcus pyogenes isolates expressing the FCT-1 pilus variant, known to be strong biofilm formers. Cell binding and biofilm formation assays using S. pyogenes in-frame deletion mutants, Lactococcus expressing heterologous FCT-1 pili and purified recombinant AP1_M6, indicated that this pilin is a strong cell adhesin that is also involved in bacterial biofilm formation. Moreover, we show that AP1_M6 establishes homophilic interactions that mediate inter-bacterial contact, possibly promoting bacterial colonization of target epithelial cells in the form of three-dimensional microcolonies. Finally, AP1_M6 knockout mutants were less virulent in mice, indicating that this protein is also implicated in GAS systemic infection.

Becherelli, Marco; Manetti, Andrea G O; Buccato, Scilla; Viciani, Elisa; Ciucchi, Laura; Mollica, Giulia; Grandi, Guido; Margarit, Imma

2012-01-01

199

Ig-binding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system.  

PubMed

Streptococcus pyogenes, an important human pathogen, expresses several proteins that interact with the immune system of the host. Among the proteins isolated from different bacterial strains are antiphagocytic M proteins, Ig Fc-binding proteins and exotoxins that act as superantigens. Here we report a novel interaction between S. pyogenes and the human immune system, the ability of most S. pyogenes strains to bind human C4BP (C4b-binding protein), a 570-kDa serum protein that inhibits the classical pathway of complement activation. Molecular analysis of three different streptococcal strains demonstrated that C4BP binds to protein Arp or protein Sir, two Ig-binding cell surface molecules that are members of the M protein family. These bacterial proteins have separate high affinity binding sites for Ig and for C4BP, as demonstrated by inhibition tests and binding assays with purified components. A single streptococcal cell surface molecule, Arp or Sir, therefore combines the abilities to bind Ig and C4BP, two high m.w. components of the immune system. Two bacterial strains expressing Arp or Sir were shown to selectively bind C4BP in whole human serum, suggesting that S. pyogenes also binds C4BP in the infected host. When bound to streptococcal cells, C4BP retained its ability to act as a cofactor in the degradation of C4b by factor I. These results indicate that many strains of S. pyogenes interfere with the classical pathway of complement activation by binding C4BP to the bacterial cell surface. PMID:7995956

Thern, A; Stenberg, L; Dahlbäck, B; Lindahl, G

1995-01-01

200

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

PubMed Central

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.

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

2012-01-01

201

An iron-binding protein, Dpr, decreases hydrogen peroxide stress and protects Streptococcus pyogenes against multiple stresses.  

PubMed

Streptococcus pyogenes does not produce catalase, but it can grow in aerobic environments and survive in the presence of peroxide. One of the stress proteins of this organism, peroxide resistance protein (Dpr), has been studied to examine its role in resistance to hydrogen peroxide, but the protective mechanism of Dpr is not clear. The aim of this study was to characterize the dpr gene and its role in dealing with different stresses. A dpr deletion mutant was constructed by double-crossover mutagenesis. The dpr mutant was more sensitive to H(2)O(2), and complementation could partially restore the defect in the mutant. Pretreatment with the iron chelator deferoxamine mesylate rescued the survival activity of the mutant under oxidative stress conditions. The dpr mutant also showed a low survival rate in the long-term stationary phase, when it was treated with extreme acids, and under alkaline pH conditions compared to the wild-type strain. The growth of the dpr mutant was slower than that of the wild-type strain in iron-limiting conditions. The dpr mutant showed high sensitivity to iron and zinc but not to manganese, copper, nickel, and calcium. Recombinant Dpr protein was purified and showed iron-binding activity, whereas no DNA-binding activity was found. These data indicate that an iron-binding protein, Dpr, provides protection from hydrogen peroxide stress by preventing the Fenton reaction, and Dpr was identified as a novel stress protein that protects against several stresses in group A streptococci. PMID:18541662

Tsou, Chih-Cheng; Chiang-Ni, Chuan; Lin, Yee-Shin; Chuang, Woei-Jer; Lin, Ming-T; Liu, Ching-Chuan; Wu, Jiunn-Jong

2008-06-09

202

Role of RopB in Growth Phase Expression of the SpeB Cysteine Protease of Streptococcus pyogenes  

PubMed Central

The Rgg family of transcription regulators is widely distributed among gram-positive bacteria; however, how the members of this family control transcription is poorly understood. In the pathogen Streptococcus pyogenes, the Rgg family member RopB is required for transcription of the gene that encodes the secreted SpeB cysteine protease. Expression of the protease follows distinct kinetics that involves control of transcription in response to the growth phase. In this study, the contribution of RopB to growth phase control was examined. The gene encoding the protease (speB) and ropB are transcribed divergently from a 940-bp intergenic region. Primer extension analyses, in conjunction with reporter fusion studies, revealed that the major region controlling the transcription of both speB and ropB is adjacent to ropB and that the promoters for the two genes likely overlap. Furthermore, it was found that RopB is a DNA-binding protein that specifically binds to sequences in this control region. The interrelationship between ropB and speB expression was further reflected in the observation that transcription of ropB itself is subject to growth phase control. However, while expression of ropB from a promoter expressed during the early logarithmic phase of growth could complement a ropB deletion mutant, ectopic expression of ropB did not uncouple the expression of speB from its growth phase signal. These data implicate other factors in growth phase control and suggest that regulation of ropB expression itself is not the central mechanism of control.

Neely, Melody N.; Lyon, William R.; Runft, Donna L.; Caparon, Michael

2003-01-01

203

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

PubMed

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

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

2012-08-20

204

Heterologous Expression of Ralp3 in Streptococcus pyogenes M2 and M6 Strains Affects the Virulence Characteristics  

PubMed Central

Background Ralp3 is a transcriptional regulator present in a serotype specific fashion on the chromosome of the human pathogen Streptococcus pyogenes (group A streptococci, GAS). In serotypes harbouring the ralp3 gene either positive or negative effects on important metabolic and virulence genes involved in colonization and immune evasion in the human host were observed. A previous study revealed that deletion of ralp3 in a GAS M49 serotype significantly attenuated many virulence traits and caused metabolic disadvantages. This leads to two questions: (i) which kind of consequences could Ralp3 expression have in GAS serotypes naturally lacking this gene, and (ii) is Ralp3 actively lost during evolution in these serotypes. Methodology/Principal Findings We investigated the role of Ralp3 in GAS M2 and M6 pathogenesis. Both serotypes lack ralp3 on their chromosome. The heterologous expression of ralp3 in both serotypes resulted in reduced attachment to and internalization into the majority of tested epithelial cells. Both ralp3 expression strains showed a decreased ability to survive in human blood and exclusively M2::ralp3 showed decreased survival in human serum. Both mutants secreted more active SpeB in the supernatant, resulting in a higher activity compared to wild type strains. The respective M2 and M6 wild type strains outcompeted the ralp3 expression strains in direct metabolic competition assays. The phenotypic changes observed in the M2:ralp3 and M6:ralp3 were verified on the transcriptional level. Consistent with the virulence data, tested genes showed transcript level changes in the same direction. Conclusions/Significance Together these data suggest that Ralp3 can take over transcriptional control of virulence genes in serotypes lacking the ralp3 gene. Those serotypes most likely lost Ralp3 during evolution since obviously expression of this gene is disadvantageous for metabolism and pathogenesis.

Siemens, Nikolai; Kreikemeyer, Bernd

2013-01-01

205

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

PubMed Central

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.

2012-01-01

206

High-resolution crystal structure of Streptococcus pyogenes ?-NAD(+) glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface.  

PubMed

One of the virulence factors produced by Streptococcus pyogenes is ?-NAD(+) glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38-451) and the full-length IFS (residues 1-161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPNct-IFS complex, which consists of the SPN C-terminal domain (SPNct; residues 193-451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70?Ĺ resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPNct and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope. PMID:24121349

Yoon, Ji Young; An, Doo Ri; Yoon, Hye Jin; Kim, Hyoun Sook; Lee, Sang Jae; Im, Ha Na; Jang, Jun Young; Suh, Se Won

2013-09-29

207

High-resolution crystal structure of Streptococcus pyogenes ?-NAD+ glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface  

PubMed Central

One of the virulence factors produced by Streptococcus pyogenes is ?-NAD+ glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPNct–IFS complex, which consists of the SPN C-terminal domain (SPNct; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70?Ĺ resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPNct and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.

Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin; Kim, Hyoun Sook; Lee, Sang Jae; Im, Ha Na; Jang, Jun Young; Suh, Se Won

2013-01-01

208

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

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.

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

2010-01-01

209

Resistance to bacitracin in Streptococcus pyogenes from oropharyngeal colonization and noninvasive infections in Portugal was caused by two clones of distinct virulence genotypes.  

PubMed

During 2000-2007 in Lisbon, we identified 45 bacitracin-resistant Streptococcus pyogenes isolates among 1629 isolates: 24 from oropharyngeal healthy carriers (out of 1026), 21 from patients with noninvasive infections (out of 559) and zero from invasive infections (out of 44). Forty-four of those isolates, mainly of colonization, are low-level bacitracin-resistant members of the cMLS(B)-macrolide-resistant and tetracycline-susceptible emm28/ST52 clone previously detected in Europe, but only among clinical samples. One high-level bacitracin-resistant isolate, associated with a tonsillitis/pharyngitis episode, is cMLS(B)-macrolide-resistant and tetracycline-resistant member of the emm74/ST120 lineage, which was not previously known to include bacitracin-resistant isolates. The bcrABDR operon encoding an ATP-binding cassette transporter in Enterococcus faecalis was not detected among these bacitracin-resistant S. pyogenes strains. Virulence profiling indicated that genes coding for exotoxins and superantigens seem to be clone specific. This study provides an increased knowledge about specific bacitracin-resistant S. pyogenes strains, which may be useful in future investigations aiming to understand the mechanism(s) leading to bacitracin resistance and the cause(s) for differences in colonization and/or dissemination potential. PMID:19486163

Pires, Renato; Rolo, Dora; Mato, Rosario; Feio de Almeida, Joăo; Johansson, Christina; Henriques-Normark, Birgitta; Morais, Ana; Brito-Avô, António; Gonçalo-Marques, José; Santos-Sanches, Ilda

2009-05-06

210

An insert in the covS gene distinguishes a pharyngeal and a blood isolate of Streptococcus pyogenes found in the same individual  

PubMed Central

Expression of the extensive arsenal of virulence factors by Streptococcus pyogenes is controlled by many regulators, of which CovRS is one of the best characterized and can influence ?15?% of the genome. Animal models have established that mutants of covRS arise spontaneously in vivo resulting in highly invasive organisms. We analysed a pharyngeal and a blood isolate of S. pyogenes recovered from the same individual 13?days apart. The two isolates varied in many phenotypic properties including SpeB production, which were reflected in transcriptomic analyses. PFGE, multilocus sequence typing and partial sequencing of some key genes failed to show any differences except for an 11 bp insert in the covS gene in the blood isolate which caused a premature termination of transcription. Complementation of a fully functional covS gene into the blood isolate resulted in high expression of CovS and expression of speB. These results, showing a pharyngeal and a blood isolate from a single individual differing by a simple insertion, provide evidence for the model that regulatory gene mutations allow S. pyogenes to invade different niches in the body.

Garcia, Alan F.; Abe, Lucienne M.; Erdem, Guliz; Cortez, Chari L.; Kurahara, David; Yamaga, Karen

2010-01-01

211

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

PubMed Central

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.

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

2011-01-01

212

Inflammatory Bowel Disease and Streptococcus bovis  

Microsoft Academic Search

Evidence suggests a trend for a higher fecal carriage rate of Streptococcus bovis in adult patients with inflammatory bowel disease (IBD). This study defines the fecal carriage rate of S. bovis among children with IBD compared to controls. Subjects with IBD were prospectively enrolled from the patient population of a pediatric gastroenterology practice. Stool samples from IBD patients as well

Jonathan E. Teitelbaum; Maria Triantafyllopoulou

2006-01-01

213

Changing epidemiology of Streptococcus pyogenes emm types and associated invasive and noninvasive infections in Southern Taiwan.  

PubMed

A total of 242 isolates were recovered from 76 patients with invasive diseases, 89 with scarlet fever, and 77 with pharyngitis. The most frequent emm types were types 12 (43.4%), 4 (18.2%), and 1 (16.9%). emm12 reemerged in 2005 and peaked in 2007. emm11 was recovered only from patients with invasive disease. PMID:19515840

Su, Yu-Fang; Wang, Shih-Min; Lin, Ya-Lan; Chuang, Woei-Jer; Lin, Yee-Shin; Wu, Jiunn-Jong; Lin, Ming T; Liu, Ching-Chuan

2009-06-10

214

Changing Epidemiology of Streptococcus pyogenes emm Types and Associated Invasive and Noninvasive Infections in Southern Taiwan?  

PubMed Central

A total of 242 isolates were recovered from 76 patients with invasive diseases, 89 with scarlet fever, and 77 with pharyngitis. The most frequent emm types were types 12 (43.4%), 4 (18.2%), and 1 (16.9%). emm12 reemerged in 2005 and peaked in 2007. emm11 was recovered only from patients with invasive disease.

Su, Yu-Fang; Wang, Shih-Min; Lin, Ya-Lan; Chuang, Woei-Jer; Lin, Yee-Shin; Wu, Jiunn-Jong; Lin, Ming T.; Liu, Ching-Chuan

2009-01-01

215

Complete Genome Sequence of emm1 Streptococcus pyogenes A20, a Strain with an Intact Two-Component System, CovRS, Isolated from a Patient with Necrotizing Fasciitis  

PubMed Central

Here, we announce the complete sequence of Streptococcus pyogenes A20. This strain was isolated from a patient with necrotizing fasciitis. Given that A20 harbors an intact two-component system, CovRS, the discovery of its genome sequence provides more insight into the pathogenesis of a pandemic emm1 strain.

Zheng, Po-Xing; Chung, Kun-Ta; Chiang-Ni, Chuan; Wang, Shu-Ying; Tsai, Pei-Jane; Chuang, Woei-Jer; Lin, Yee-Shin; Liu, Ching-Chuan

2013-01-01

216

Rise and Persistence of Global M1T1 Clone of Streptococcus pyogenes  

Microsoft Academic Search

The resurgence of severe invasive group A streptococcal (GAS) infections in the 1980s is a typical example of the reemergence of an infectious disease. We found that this resurgence is a consequence of the diversification of particular strains of the bacteria. Among these strains is a highly virulent subclone of serotype M1T1 that has exhibited unusual epidemiologic features and virulence,

Ramy K. Aziz; Malak Kotb

2008-01-01

217

Environmental Acidification Drives S. pyogenes Pilus Expression and Microcolony Formation on Epithelial Cells in a FCT-Dependent Manner  

Microsoft Academic Search

Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen responsible for a diverse variety of diseases, including pharyngitis, skin infections, invasive necrotizing fasciitis and autoimmune sequelae. We have recently shown that GAS cell adhesion and biofilm formation is associated with the presence of pili on the surface of these bacteria. GAS pilus proteins are encoded in the FCT

Andrea G. O. Manetti; Thomas Köller; Marco Becherelli; Scilla Buccato; Bernd Kreikemeyer; Andreas Podbielski; Guido Grandi; Immaculada Margarit

2010-01-01

218

Rise and Persistence of Global M1T1 Clone of Streptococcus pyogenes  

PubMed Central

The resurgence of severe invasive group A streptococcal infections in the 1980s is a typical example of the reemergence of an infectious disease. We found that this resurgence is a consequence of the diversification of particular strains of the bacteria. Among these strains is a highly virulent subclone of serotype M1T1 that has exhibited unusual epidemiologic features and virulence, unlike all other streptococcal strains. This clonal strain, commonly isolated from both noninvasive and invasive infection cases, is most frequently associated with severe invasive diseases. Because of its unusual prevalence, global spread, and increased virulence, we investigated the unique features that likely confer its unusual properties. In doing so, we found that the increased virulence of this clonal strain can be attributed to its diversification through phage mobilization and its ability to sense and adapt to different host environments; accordingly, the fittest members of this diverse bacterial community are selected to survive and invade host tissue.

Kotb, Malak

2008-01-01

219

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

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.

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

2011-01-01

220

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

PubMed

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

Alotaibi, Hend M

2009-06-01

221

Description of macrolide-resistant and potential virulent clones of Streptococcus pyogenes causing asymptomatic colonization during 2000-2006 in the Lisbon area.  

PubMed

The asymptomatic oropharyngeal colonization rate by Streptococcus pyogenes was 10.7% in children (901 among 8,405 children 0-16 years old) and 3.3% in adults (37 among 1,126 households of children) in the Lisbon area during 2000-2006. Macrolide-resistant S. pyogenes from children (n = 149) was variable with time: 9.8-10.7% in 2000-2002, 28.1% in 2003, 19.6-2.7% in 2004-2005 and 14.6% in 2006. Eight lineages (97.3% of isolates) were identified based on at least 80% similarity of PFGE patterns, T types, emm types and multilocus sequence types (ST). The elevated frequency of macrolide resistance was associated with M phenotype lineages I (emm12/ST36) and V (emm4, emm75/ST39 and a novel emmstMrp6 type) and with one cMLS(B) lineage IV (emm28/ST52) known to be associated with upper respiratory tract and invasive infections. Significant associations (p < 0.05) between emm type/virulence genotype were found, such as emm1/speA (+) ssa (-), emm4/ssa (+) prtF1 (+), emm12/speA (-) ssa (-). The high prevalence (>20%) of speC, prtF1 or ssa was probably caused either by clonal dissemination (speC), or to horizontal gene transfer events (prtF1 and ssa). This report contributes to a better understanding of the molecular epidemiology and evolution of macrolide-resistant S. pyogenes causing symptom-free oropharyngeal colonization. These colonizing strains carry macrolide resistance and virulence genes capable of being transferred to other bacterial species sharing the same niche. PMID:22012657

Pires, R; Rolo, D; Morais, A; Brito-Avô, A; Johansson, C; Henriques-Normark, B; Gonçalo-Marques, J; Santos-Sanches, I

2011-10-21

222

The transcriptional terminator sequences downstream of the covR gene terminate covR/S operon transcription to generate covR monocistronic transcripts in Streptococcus pyogenes.  

PubMed

CovR/S is an important two component regulatory system, which regulates about 15% of the gene expression in Streptococcus pyogenes. The covR/S locus was identified as an operon generating an RNA transcript around 2.5-kb in size. In this study, we found the covR/S operon produced three RNA transcripts (around 2.5-, 1.0-, and 0.8-kb in size). Using RNA transcriptional terminator sequence prediction and transcriptional terminator analysis, we identified two atypical rho-independent terminator sequences downstream of the covR gene and showed these terminator sequences terminate RNA transcription efficiently. These results indicate that covR/S operon generates covR/S transcript and monocistronic covR transcripts. PMID:18824088

Chiang-Ni, Chuan; Tsou, Chih-Cheng; Lin, Yee-Shin; Chuang, Woei-Jer; Lin, Ming-T; Liu, Ching-Chuan; Wu, Jiunn-Jong

2008-09-11

223

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

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.

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

1996-01-01

224

Regulation of SpeB in Streptococcus pyogenes by pH and NaCl: a Model for In Vivo Gene Expression†  

PubMed Central

For a pathogen such as Streptococcus pyogenes, ecological success is determined by its ability to sense the environment and mount an appropriate adaptive transcriptional response. Thus, determining conditions for analyses of gene expression in vitro that are representative of the in vivo environment is critical for understanding the contributions of transcriptional response pathways to pathogenesis. In this study, we determined that the gene encoding the SpeB cysteine protease is up-regulated over the course of infection in a murine soft-tissue model. Conditions were identified, including growth phase, acidic pH, and an NaCl concentration of <0.1 M, that were required for expression of speB in vitro. Analysis of global expression profiles in response to these conditions in vitro identified a set of coregulated genes whose expression patterns showed a significant correlation with that of speB when examined during infection of murine soft tissues. This analysis revealed that a culture medium that promotes high levels of SpeB expression in vitro produced an expression profile that showed significant correlation to the profile observed in vivo. Taken together, these studies establish culture conditions that mimic in vivo expression patterns; that growth phase, pH, and NaCl may mimic relevant cues sensed by S. pyogenes during infection; and that identification of other environmental cues that alter expression of speB in vitro may provide insight into the signals that direct global patterns of gene expression in vivo.

Loughman, Jennifer A.; Caparon, Michael

2006-01-01

225

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

PubMed Central

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.

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

2012-01-01

226

In vitro activity of several antimicrobial agents against 1003 isolates of Streptococcus pyogenes collected from Western Canada  

Microsoft Academic Search

Streptococcuspyogenes is a common pathogen which may be associated with significant morbidity and mortality. Recent information is not readily available, in Canada, regarding the susceptibility of clinical isolates to penicillin, extended spectrum and\\/or newer agents. We collected and tested 1003 isolates of S. pyogenes to seven antimicrobial agents and found the following susceptibility rates: azithromycin 97%, ceftriaxone 100%, ciprofloxacin 99.4%,

J. M Blondeau; D Church; Y Yaschuk; J Bjarnason

1999-01-01

227

Recovery of Streptococcus iniae from Diseased Fish Previously Vaccinated with a Streptococcus Vaccine  

PubMed Central

Streptococcus iniae was recovered from diseased rainbow trout (Oncorhynchus mykiss, Walbaum) previously vaccinated against streptococcosis. PCR and serological methods indicate the presence of a new serotype in the diseased fish.

Bachrach, Gilad; Zlotkin, Amir; Hurvitz, Avshalom; Evans, Donald L.; Eldar, Avi

2001-01-01

228

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

PubMed Central

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.

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

2011-01-01

229

SpyA is a membrane-bound ADP-ribosyltransferase of Streptococcus pyogenes which modifies a streptococcal peptide, SpyB  

PubMed Central

Summary All sequenced genomes of Streptococcus pyogenes (Group A Streptococcus, GAS) encode a protein, SpyA, with homology to C3-like ADP-ribosyltransferase toxins. SpyA is a novel virulence factor which plays a role in pathogenesis in a mouse model of soft-tissue infection. In this study we demonstrate that SpyA is a surface-exposed membrane protein which is anchored to the streptococcal membrane by an N-terminal transmembrane sequence. We identified a small gene upstream of spyA, designated spyB, which encodes a peptide of 35 amino acids, and is co-transcribed with spyA. Expression of spyBA is strongly influenced by translational coupling: mutational inactivation of spyB translation completely abolishes translation of spyA. spyB expression increases with increasing cell density and reaches its maximum at late exponential growth phase. The SpyB N-terminus is predicted to fold into an amphipathic ?-helix, a structural motif that targets a protein to the cytoplasmic membrane. Consistent with the prediction, we found that a SpyB fusion with peptide affinity tags is located in the streptococcal membrane. An ADP-ribosylation assay with recombinant SpyA demonstrated that SpyA modifies SpyB. Thus, our study suggests that ADP-ribosylation of SpyB may be an important function of SpyA.

Korotkova, Natalia; Hoff, Jessica S.; Becker, Devon M.; Quinn, John Kyle Heggen; Icenogle, Laura M.; Moseley, Steve L.

2012-01-01

230

The ribonucleases J1 and J2 are essential for growth and have independent roles in mRNA decay in Streptococcus pyogenes.  

PubMed

The paralogous ribonucleases J1 and J2, recently identified in Bacillus subtilis, have both endoribonucleolytic and 5'-to-3' exoribonucleolytic activities and participate in degradation and regulatory processing of mRNA. RNases J1 and J2 have partially overlapping target specificities, but only RNase J1 is essential for B. subtilis growth. Because mRNA decay is important in regulation of virulence factors of Streptococcus pyogenes (the group A streptococcus, GAS), we investigated the role of these newly described RNases in GAS. We found that conditional mutants for both RNases J1 and J2 require induction for growth, so we conclude that, unlike the case in B. subtilis, both of these RNases are essential for GAS growth, and therefore their functions are not redundant. We compared decay of representatives of the two classes of messages we had previously identified: Class I, which decay rapidly in exponential and stationary phase of growth (hasA and gyrA), and Class II, which are stable in stationary phase and exhibit a biphasic decay curve in exponential phase (sagA and sda). We report that RNases J1 and J2 affect the rate of decay of Class I messages and the length of the first phase in decay of Class II messages. PMID:20025665

Bugrysheva, Julia V; Scott, June R

2009-12-16

231

Recurrent pyogenic cholangitis  

Microsoft Academic Search

Background: Recurrent pyogenic cholangitis is a complex biliary tract disease characterized by intrahepatic pigment stones, endemic to Southeast Asia and seen with increasing frequency in the United States. The purpose of this study was to review the management of this disorder in a county hospital.Methods: A retrospective review of 45 patients with recurrent pyogenic cholangitis evaluated between 1984 and 1995.

HobartW Harris; ZindabaL Kumwenda; Shyr-Ming Sheen-Chen; Amish Shah; WilliamP Schecter

1998-01-01

232

EndoS from Streptococcus pyogenes is hydrolyzed by the cysteine proteinase SpeB and requires glutamic acid 235 and tryptophans for IgG glycan-hydrolyzing activity  

Microsoft Academic Search

BACKGROUND: The endoglycosidase EndoS and the cysteine proteinase SpeB from the human pathogen Streptococcus pyogenes are functionally related in that they both hydrolyze IgG leading to impairment of opsonizing antibodies and thus enhance bacterial survival in human blood. In this study, we further investigated the relationship between EndoS and SpeB by examining their in vitro temporal production and stability and

Maria Allhorn; Arne Olsén; Mattias Collin

2008-01-01

233

Animal Models of Streptococcus pneumoniae Disease  

PubMed Central

Summary: Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.

Chiavolini, Damiana; Pozzi, Gianni; Ricci, Susanna

2008-01-01

234

Streptococcus pyogenes c-di-AMP Phosphodiesterase, GdpP, Influences SpeB Processing and Virulence  

PubMed Central

Small cyclic nucleotide derivatives are employed as second messengers by both prokaryotes and eukaryotes to regulate diverse cellular processes responding to various signals. In bacteria, c-di-AMP has been discovered most recently, and some Gram-positive pathogens including S. pyogenes use this cyclic nucleotide derivative as a second messenger instead of c-di-GMP, a well-studied important bacterial second messenger. GdpP, c-di-AMP phosphodiesterase, is responsible for degrading c-di-AMP inside cells, and the cellular role of GdpP in S. pyogenes has not been examined yet. To test the cellular role of GdpP, we created a strain with a nonpolar inframe deletion of the gdpP gene, and examined the properties of the strain including virulence. From this study, we demonstrated that GdpP influences the biogenesis of SpeB, the major secreted cysteine protease, at a post-translational level, susceptibility to the beta lactam antibiotic ampicillin, and is necessary for full virulence in a murine subcutaneous infection model.

Cho, Kyu Hong; Kang, Song Ok

2013-01-01

235

Streptococcus pyogenes Ser/Thr Kinase-regulated Cell Wall Hydrolase Is a Cell Division Plane-recognizing and Chain-forming Virulence Factor*  

PubMed Central

Cell division and cell wall synthesis are closely linked complex phenomena and play a crucial role in the maintenance and regulation of bacterial virulence. Eukaryotic-type Ser/Thr kinases reported in prokaryotes, including that in group A Streptococcus (GAS) (Streptococcus pyogenes Ser/Thr kinase (SP-STK)), regulate cell division, growth, and virulence. The mechanism of this regulation is, however, unknown. In this study, we demonstrated that SP-STK-controlled cell division is mediated under the positive regulation of secretory protein that possesses a cysteine and histidine-dependent aminohydrolases/peptidases (CHAP) domain with functionally active cell wall hydrolase activity (henceforth named as CdhA (CHAP-domain-containing and chain-forming cell wall hydrolase). Deletion of the CdhA-encoding gene resulted in severe cell division and growth defects in GAS mutants. The mutant expressing the truncated CdhA (devoid of the CHAP domain), although displayed no such defects, it became attenuated for virulence in mice and highly susceptible to cell wall-acting antibiotics, as observed for the mutant lacking CdhA. When CdhA was overexpressed in the wild-type GAS as well as in heterologous strains, Escherichia coli and Staphylococcus aureus, we observed a distinct increase in bacterial chain length. Our data reveal that CdhA is a multifunctional protein with a major function of the N-terminal region as a cell division plane-recognizing domain and that of the C-terminal CHAP domain as a virulence-regulating domain. CdhA is thus an important therapeutic target.

Pancholi, Vijay; Boel, Gregory; Jin, Hong

2010-01-01

236

Purification, crystallization and preliminary X-ray analysis of native and selenomethionine class I tagatose-1,6-bisphosphate aldolase from Streptococcus pyogenes.  

PubMed

Tagatose-1,6-bisphosphate aldolase (EC 4.1.2.40) is situated at the branching of the tagatose-6-phosphate and Embden-Meyerhof-Parnas (glycolysis) metabolic pathways, where it catalyzes the reversible cleavage of tagatose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. The recombinant protein from Streptococcus pyogenes was overexpressed in Escherichia coli in its native and selenomethionine-derivative forms and purified using ion-exchange and hydrophobic interaction chromatography. Orthorhombic crystals suitable for structural analysis were obtained by the hanging-drop vapour-diffusion method for both isoforms. The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 63.7, b = 108.1, c = 238.7 A for the native form and a = 64.1, b = 108.3, c = 239.8 A for the selenomethionine derivative. The asymmetric unit contains four protomers, corresponding to a crystal volume per protein weight (V(M)) of 2.8 A(3) Da(-1) and a solvent content of 56% by volume. PMID:14993682

Liotard, Brigitte; Sygusch, Jurgen

2004-02-25

237

MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin-mediated translocation system genes.  

PubMed

As a prerequisite for colonization or causing local infections, Streptococcus pyogenes (group A streptococci, GAS) need to specifically adhere to eukaryotic cell surfaces. Predominantly responsible adhesin genes are contained in a genotype-specific pattern within the FCT region of the GAS genome. In this study, MsmR, belonging to AraC/XylS type transcriptional regulators, was identified in the FCT region as a positive regulator of the major fibronectin-binding adhesin protein F2 in a serotype M49 strain. Compared with the wild-type strain, the msmR mutant showed reduced binding to immobilized fibronectin and decreased adherence to and internalization into human pharyngeal epithelial cells. These results suggested that altered levels of fibronectin-binding proteins in the mutant affect eukaryotic cell attachment and internalization. Complete transcriptome and reporter fusion assay data revealed that MsmR positively regulates FCT region genes including Nra and cytolysin-mediated translocation system genes. Consistent with the genetic data, the mutant showed attenuated streptolysin O activity and eukaryotic cell cytotoxity. Direct binding of recombinant MsmR to nga, nra/cpa and prtF2 promoter regions was confirmed by EMSA assays. As prior analysis demonstrated the Nra regulator negatively affects gene expression from the FCT region, MsmR and Nra appear to adversely control crucial virulence factor expression in GAS and thus contribute to a fine-tuned balance between local destructive process and metastatic spreading of the bacteria. PMID:16045622

Nakata, Masanobu; Podbielski, Andreas; Kreikemeyer, Bernd

2005-08-01

238

Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media  

PubMed Central

Background The oral probiotic Streptococcus salivarius K12 has been shown clearly to antagonize the growth of Streptococcus pyogenes, the most important bacterial cause of pharyngeal infections in humans, by releasing two bacteriocins named salivaricin A2 and salivaricin B. Unpublished observations indicate that it can also antagonize the growth of other bacteria involved in acute otitis media. Because of its ability to colonize the oral cavity and its safety profile, we have tested its efficacy in reducing the incidence of streptococcal pharyngitis and/or tonsillitis and episodes of acute otitis media. Methods We enrolled 82 children, including 65 with and 17 without a recent diagnosis of recurrent oral streptococcal pathology. Of those with recurrent pathology, 45 were treated daily for 90 days with an oral slow-release tablet containing five billion colony-forming units of S. salivarius K12 (Bactoblis®), and the remaining 20 served as an untreated control group. The 17 children without a recent diagnosis of recurrent oral pathology were used as an additional control group. After 90 days of treatment, a 6-month follow-up period without treatment was included to evaluate a possible persistent protective role for the previously administered product. Results The 41 children who completed the 90-day course of Bactoblis showed a reduction in their episodes of streptococcal pharyngeal infection (about 90%) and/or acute otitis media (about 40%), calculated by comparing infection rates in the previous year. The 90-day treatment also reduced the reported incidence of pharyngeal and ear infections by about 65% in the 6-month follow-up period during which the product was not administered. Subjects tolerated the product well, with no side effects or dropouts reported. Conclusion Prophylactic administration of S. salivarius K12 to children with a history of recurrent oral streptococcal pathology reduced episodes of streptococcal pharyngeal infections and/or tonsillitis as well as episodes of acute otitis media.

Di Pierro, Francesco; Donato, Guido; Fomia, Federico; Adami, Teresa; Careddu, Domenico; Cassandro, Claudia; Albera, Roberto

2012-01-01

239

Involvement of Lsp, a member of the LraI-lipoprotein family in Streptococcus pyogenes, in eukaryotic cell adhesion and internalization.  

PubMed

Three open reading frames (ORFs) were identified by a genome walking strategy in the genomes of serotype M49 group A streptococcal (GAS) strains CS101 and 591. These ORFs were located between the mga core regulon and the dipeptide permease operon. The deduced amino acid (aa) sequences contained signature sequences indicative of a lipoprotein (306 aa), an intracellular protein (823 aa), and a secreted peptide (66 aa), respectively. ORF1 (named Lsp for lipoprotein of Streptococcus pyogenes) and ORF2 exhibited a high degree of homology to the lmb/ORF2 genes of S. agalactiae (B. Spellerberg et al., Infect. Immun. 67:871-878, 1999). The three ORFs were found to be present in each of the 27 GAS serotype strains tested. Transcription analysis revealed a polycistronic lsp/ORF2 and a monocistronic ORF3 message that were detected primarily at the transition from exponential to stationary growth phase. lsp and ORF2 mutants, ORF2- and ORF3-luciferase reporter fusions, and antiserum against recombinant Lsp were produced to examine the biological role of these genes. Although high Zn(2+) and Cu(2+) ion concentrations decreased lsp operon expression, Lsp did not transport divalent cations as described for other LraI-type operons. The lsp mutant had reduced fibronectin binding. Although no direct binding of Lsp to fibronectin could be demonstrated, the lsp mutant showed decreased transcription of prtF2 encoding the fibronectin-binding protein F2. Both the lsp and ORF2 mutants showed decreased laminin binding. Adherence to and internalization into A549 epithelial cells of both mutants was reduced without a detectable effect on eukaryotic cell viability. The transcription of a number of virulence factors was altered in the lsp mutants and ORF2 mutants. The changes in laminin binding and eukaryotic cell internalization could be explained by changes in transcription of speB (cysteine protease) and/or the global regulators mga, csrRS, and nra. PMID:12183530

Elsner, Andrea; Kreikemeyer, Bernd; Braun-Kiewnick, Andrea; Spellerberg, Barbara; Buttaro, Bettina A; Podbielski, Andreas

2002-09-01

240

Involvement of Lsp, a Member of the LraI-Lipoprotein Family in Streptococcus pyogenes, in Eukaryotic Cell Adhesion and Internalization  

PubMed Central

Three open reading frames (ORFs) were identified by a genome walking strategy in the genomes of serotype M49 group A streptococcal (GAS) strains CS101 and 591. These ORFs were located between the mga core regulon and the dipeptide permease operon. The deduced amino acid (aa) sequences contained signature sequences indicative of a lipoprotein (306 aa), an intracellular protein (823 aa), and a secreted peptide (66 aa), respectively. ORF1 (named Lsp for lipoprotein of Streptococcus pyogenes) and ORF2 exhibited a high degree of homology to the lmb/ORF2 genes of S. agalactiae (B. Spellerberg et al., Infect. Immun. 67:871-878, 1999). The three ORFs were found to be present in each of the 27 GAS serotype strains tested. Transcription analysis revealed a polycistronic lsp/ORF2 and a monocistronic ORF3 message that were detected primarily at the transition from exponential to stationary growth phase. lsp and ORF2 mutants, ORF2- and ORF3-luciferase reporter fusions, and antiserum against recombinant Lsp were produced to examine the biological role of these genes. Although high Zn2+ and Cu2+ ion concentrations decreased lsp operon expression, Lsp did not transport divalent cations as described for other LraI-type operons. The lsp mutant had reduced fibronectin binding. Although no direct binding of Lsp to fibronectin could be demonstrated, the lsp mutant showed decreased transcription of prtF2 encoding the fibronectin-binding protein F2. Both the lsp and ORF2 mutants showed decreased laminin binding. Adherence to and internalization into A549 epithelial cells of both mutants was reduced without a detectable effect on eukaryotic cell viability. The transcription of a number of virulence factors was altered in the lsp mutants and ORF2 mutants. The changes in laminin binding and eukaryotic cell internalization could be explained by changes in transcription of speB (cysteine protease) and/or the global regulators mga, csrRS, and nra.

Elsner, Andrea; Kreikemeyer, Bernd; Braun-Kiewnick, Andrea; Spellerberg, Barbara; Buttaro, Bettina A.; Podbielski, Andreas

2002-01-01

241

Serine/Threonine Phosphatase (SP-STP), Secreted from Streptococcus pyogenes, Is a Pro-apoptotic Protein*  

PubMed Central

This investigation illustrates an important property of eukaryote-type serine/threonine phosphatase (SP-STP) of group A Streptococcus (GAS) in causing programmed cell death of human pharyngeal cells. The secretory nature of SP-STP, its elevated expression in the intracellular GAS, and the ability of wild-type GAS but not the GAS mutant devoid of SP-STP to cause apoptosis of the host cell both in vitro and in vivo suggest that GAS deploys SP-STP as an important virulence determinant to exploit host cell machinery for its own advantage during infection. The exogenously added SP-STP is able to enter the cytoplasm and subsequently traverses into the nucleus in a temporal fashion to cause apoptosis of the pharyngeal cells. The programmed cell death induced by SP-STP, which requires active transcription and de novo protein synthesis, is also caspase-dependent. Furthermore, the entry of SP-STP into the cytoplasm is dependent on its secondary structure as the catalytically inactive SP-STP with an altered structure is unable to internalize and cause apoptosis. The ectopically expressed wild-type SP-STP was found to be in the nucleus and conferred apoptosis of Detroit 562 pharyngeal cells. However, the catalytically inactive SP-STP was unable to cause apoptosis even when intracellularly expressed. The ability of SP-STP to activate pro-apoptotic signaling cascades both in the cytoplasm and in the nucleus resulted in mitochondrial dysfunctioning and perturbation in the phosphorylation status of histones in the nucleus. SP-STP thus not only functions as a virulence regulator but also as an important factor responsible for host-related pathogenesis.

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

2012-01-01

242

Mouse skin passage of a Streptococcus pyogenes Tn917 mutant of sagA/pel restores virulence, beta-hemolysis and sagA/pel expression without altering the position or sequence of the transposon  

PubMed Central

Background Streptolysin S (SLS), the oxygen-stable hemolysin of Streptococcus pyogenes, has recently been shown to be encoded by the sagA/pel gene. Mutants lacking expression of this gene were less virulent in a dermonecrotic mouse infection model. Inactivation of the sagA/pel gene affect the expression of a variety of virulence factors in addition to the hemolysin. Insertion of a Tn917 transposon into the promoter region of the sagA/pel gene of S. pyogenes isolate CS101 eliminated expression of SLS, as well as decreased expression of the streptococcal pyrogenic exotoxin B, streptokinase and M protein. Results In this study a mouse skin air sac model was utilized to analyze the effect of biological pressures on expression of SLS and other sagA/pel regulated gene products. The insertion delayed the lethal effect of S. pyogenes in a mouse skin infection model. Despite this, bacteria could be cultured from the kidneys 72 hours post infection. These kidney-recovered isolates were ?-hemolytic despite the transposon being present in its original location and had equivalent virulence to the wild type isolate when re-injected into naive mice. Northern blot analysis of the kidney-recovered isolates confirmed that transcription of sagA/pel was restored; however the expression of all sagA/pel regulated genes was not restored to wild type levels. Conclusions These results show that biological pressure present in the mouse can select for variants with altered expression of key virulence factor genes in S. pyogenes.

Eberhard, Thomas H; Sledjeski, Darren D; Boyle, Michael DP

2001-01-01

243

The molecular basis of Streptococcus equi infection and disease.  

PubMed

Streptococcus equi is the aetiological agent of strangles, one of the most prevalent diseases of the horse. The animal suffering and economic burden associated with this disease necessitate effective treatment. Current antibiotic therapy is often ineffective and thus recent attention has focused on vaccine development. A systematic understanding of S. equi virulence, leading to the identification of targets to which protective immunity can be directed, is a prerequisite of the development of such a vaccine. Here, the virulence factors of S. equi are reviewed. PMID:11932201

Harrington, Dean J; Sutcliffe, Iain C; Chanter, Neil

2002-04-01

244

A novel double-tryptophan peptide pheromone is conserved in mutans and pyogenic Streptococci and Controls Competence in Streptococcus mutans via an Rgg regulator  

PubMed Central

Summary All streptococcal genomes encode the alternative sigma factor SigX and 21 SigX-dependent proteins required for genetic transformation, yet no pyogenic streptococci are known to develop competence. Resolving this paradox may depend on understanding the regulation of sigX. We report the identification of a regulatory circuit linked to the sigX genes of both mutans and pyogenic streptococci that uses a novel small, double-tryptophan-containing competence-inducing peptide (CIP) pheromone. In both groups, the CIP gene, which we designate comS, and sigX have identical, noncanonical promoters consisting of 9-bp inverted repeats separated from a ?10 hexamer by 19 bp. comS is adjacent to a gene encoding a putative transcription factor of the Rgg family and is regulated by its product, which we designate ComR. Deletion of comR or comS in S. mutans abolished transformability, as did deletion of the oligopeptide permease subunit oppD, suggesting that CIP is imported. Providing S. mutans with synthetic fragments of CIP revealed that seven C-terminal residues, including the WW motif, cause robust induction of both sigX and the competent state. We propose that this circuit is the proximal regulator of sigX in S. mutans, and we infer that it controls competence in a parallel way in all pyogenic streptococci.

Mashburn-Warren, Lauren; Morrison, Donald A.; Federle, Michael J.

2010-01-01

245

The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region.  

PubMed

Many Streptococcus pyogenes (group A streptococcus [GAS]) virulence factor- and transcriptional regulator-encoding genes cluster together in discrete genomic regions. Nra is a central regulator of the FCT region. Previous studies exclusively described Nra as a transcriptional repressor of adhesin and toxin genes. Here transcriptome and proteome analysis of a serotype M49 GAS strain and an isogenic Nra mutant of this strain revealed the complete Nra regulon profile. Nra is active in all growth phases tested, with the largest regulon in the transition phase. Almost exclusively, virulence factor-encoding genes are repressed by Nra; these genes include the GAS pilus operon, the capsule synthesis operon, the cytolysin-mediated translocation system genes, all Mga region core virulence genes, and genes encoding other regulators, like the Ihk/Irr system, Rgg, and two additional RofA-like protein family regulators. Surprisingly, our experiments revealed that Nra additionally acts as a positive regulator, mostly for genes encoding proteins and enzymes with metabolic functions. Epidemiological investigations revealed strong genetic linkage of one particular Nra-repressed regulator, Ralp3 (SPy0735), with a gene encoding Epf (extracellular protein factor from Streptococcus suis). In a serotype-specific fashion, this ralp3 epf gene block is integrated, most likely via transposition, into the eno sagA virulence gene block, which is present in all GAS serotypes. In GAS serotypes M1, M4, M12, M28, and M49 this novel discrete genetic region is therefore designated the eno ralp3 epf sagA (ERES) pathogenicity region. Functional experiments showed that Epf is a novel GAS plasminogen-binding protein and revealed that Ralp3 activity counteracts Nra and MsmR regulatory activity. In addition to the Mga and FCT regions, the ERES region is the third discrete chromosomal pathogenicity region. All of these regions are transcriptionally linked, adding another level of complexity to the known GAS growth phase-dependent regulatory network. PMID:17893125

Kreikemeyer, Bernd; Nakata, Masanobu; Köller, Thomas; Hildisch, Hendrikje; Kourakos, Vassilios; Standar, Kerstin; Kawabata, Shigetada; Glocker, Michael O; Podbielski, Andreas

2007-09-24

246

Pyogenic sacroiliitis  

SciTech Connect

Seven definite and three probable cases of pyogenic sacroiliitis are presented and compared to 72 cases found in the English literature. Patients may present with a subacute localized or an acute systemic illness. Six of our patients were parenteral drug abusers. Sacroiliac uptake of gallium 67 citrate and/or technetium 99m pyrophosphate suggested the diagnosis which was confirmed by fluoroscopically controlled joint aspiration when blood cultures were sterile. Gram-negative organisms, group B streptococci and a Staphylococcus were isolated. Antibiotic treatment for four to six weeks was uniformly successful. Surgery should be reserved for abscess or sequestrum formation, neither of which were encountered in this series.

Gordon, G.; Kabins, S.A.

1980-07-01

247

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

PubMed Central

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.

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

2013-01-01

248

StreptInCor: a candidate vaccine epitope against S. pyogenes infections induces protection in outbred mice.  

PubMed

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

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

2013-04-08

249

Bacteriological study of pyogenic meningitis with special reference to latex agglutination.  

PubMed

Bacterial meningitis is an important and frequent devastating disease. The present study was carried out to determine the prevalence of pyogenic meningitis in our hospital in children and to find out the sensitivity of Gram stain, CRP and latex agglutination tests for the diagnosis of pyogenic meningitis from CSF sample. Out of 150 CSF samples studied, 40 were diagnosed as pyogenic meningitis. H. influenzae was the commonest organism (22.5%), followed by Streptococcus pneumoniae 15%, Staphylococcus aureus--10%, Acinetobacter species and coagulase negative Stapylococci 7.5% each, E-coli 5%, and a case each of Klebsiella species, Group B streptococci, Proteus, Pseudomonas and Enterococci. The sensitivity of Gram stain and Latex agglutination test was 90% and that of CRP test was 62.5%. As most of the cases included in our study were treated earlier, the culture positivity was only 62.5%. Hence, Gram stain and/or latex agglutination tests, if done properly are most rapid and reliable tests for the diagnosis of pyogenic meningitis. PMID:17474275

Viswanath, G; Praveen; Hanumanthappa, A R; Chandrappa, N R; Mahesh, C Baragundi

2007-01-01

250

Nucleic acids and proteins from Streptococcus groups A and B  

US Patent & Trademark Office Database

The invention provides proteins from group B streptococcus (Streptococcus agalactiae) and group A streptococcus (Streptococcus pyogenes), including amino acid sequences and the corresponding nucleotide sequences. Data are given to show that the proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics. The proteins are also targets for antibiotics.

Telford; John (Monteriggioni, IT); Masignani; Vega (Siena, IT); Scarselli; Maria (Siena, IT); Grandi; Guido (Segrate, IT); Tettelin; Herve (Rockville, MD); Fraser; Claire (Clarksville, MD)

2013-04-30

251

Complement-mediated Opsonization of Invasive Group A Streptococcus pyogenes Strain AP53 Is Regulated by the Bacterial Two-component Cluster of Virulence Responder/Sensor (CovRS) System.  

PubMed

Group A Streptococcus pyogenes (GAS) strain AP53 is a primary isolate from a patient with necrotizing fasciitis. These AP53 cells contain an inactivating mutation in the sensor component of the cluster of virulence (cov) responder (R)/sensor (S) two-component gene regulatory system (covRS), which enhances the virulence of the primary strain, AP53/covR(+)S(-). However, specific mechanisms by which the covRS system regulates the survival of GAS in humans are incomplete. Here, we show a key role for covRS in the regulation of opsonophagocytosis of AP53 by human neutrophils. AP53/covR(+)S(-) cells displayed potent binding of host complement inhibitors of C3 convertase, viz. Factor H (FH) and C4-binding protein (C4BP), which concomitantly led to minimal C3b deposition on AP53 cells, further showing that these plasma protein inhibitors are active on GAS cells. This resulted in weak killing of the bacteria by human neutrophils and a corresponding high death rate of mice after injection of these cells. After targeted allelic alteration of covS(-) to wild-type covS (covS(+)), a dramatic loss of FH and C4BP binding to the AP53/covR(+)S(+) cells was observed. This resulted in elevated C3b deposition on AP53/covR(+)S(+) cells, a high level of opsonophagocytosis by human neutrophils, and a very low death rate of mice infected with AP53/covR(+)S(+). We show that covRS is a critical transcriptional regulator of genes directing AP53 killing by neutrophils and regulates the levels of the receptors for FH and C4BP, which we identify as the products of the fba and enn genes, respectively. PMID:23928307

Agrahari, Garima; Liang, Zhong; Mayfield, Jeffrey A; Balsara, Rashna D; Ploplis, Victoria A; Castellino, Francis J

2013-08-08

252

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

PubMed Central

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%.

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

253

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

PubMed

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

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; Chae, Sung-Hwa; Seo, Jung Soo

2013-10-03

254

Streptococcus-Zebrafish Model of Bacterial Pathogenesis  

PubMed Central

Due to its small size, rapid generation time, powerful genetic systems, and genomic resources, the zebrafish has emerged as an important model of vertebrate development and human disease. Its well-developed adaptive and innate cellular immune systems make the zebrafish an ideal model for the study of infectious diseases. With a natural and important pathogen of fish, Streptococcus iniae, we have established a streptococcus- zebrafish model of bacterial pathogenesis. Following injection into the dorsal muscle, zebrafish developed a lethal infection, with a 50% lethal dose of 103 CFU, and died within 2 to 3 days. The pathogenesis of infection resembled that of S. iniae in farmed fish populations and that of several important human streptococcal diseases and was characterized by an initial focal necrotic lesion that rapidly progressed to invasion of the pathogen into all major organ systems, including the brain. Zebrafish were also susceptible to infection by the human pathogen Streptococcus pyogenes. However, disease was characterized by a marked absence of inflammation, large numbers of extracellular streptococci in the dorsal muscle, and extensive myonecrosis that occurred far in advance of any systemic invasion. The genetic systems available for streptococci, including a novel method of mutagenesis which targets genes whose products are exported, were used to identify several mutants attenuated for virulence in zebrafish. This combination of a genetically amenable pathogen with a well-defined vertebrate host makes the streptococcus-zebrafish model of bacterial pathogenesis a powerful model for analysis of infectious disease.

Neely, Melody N.; Pfeifer, John D.; Caparon, Michael

2002-01-01

255

Pyogenic Liver Abscess with a Focus on Klebsiella pneumoniae as a Primary Pathogen: An Emerging Disease with Unique Clinical Characteristics  

Microsoft Academic Search

OBJECTIVES:Pyogenic liver abscess is a common intraabdominal infection. Historically, Escherichia coli (E. coli) has been the predominant causative agent. Klebsiella liver abscess (KLA) was first reported in Taiwan and has surpassed E. coli as the number one isolate from patients with hepatic abscesses in that country and reports from other countries, including the United States, have increased. We examined the

Edith R. Lederman; Nancy F. Crum

2005-01-01

256

Mosaic Prophages with Horizontally Acquired Genes Account for the Emergence and Diversification of the Globally Disseminated M1T1 Clone of Streptococcus pyogenes  

Microsoft Academic Search

The recrudescence of severe invasive group A streptococcal (GAS) diseases has been associated with rela- tively few strains, including the M1T1 subclone that has shown an unprecedented global spread and prevalence and high virulence in susceptible hosts. To understand its unusual epidemiology, we aimed to identify unique genomic features that differentiate it from the fully sequenced M1 SF370 strain. We

Ramy K. Aziz; Robert A. Edwards; William W. Taylor; Donald E. Low; Allison McGeer; Malak Kotb

2005-01-01

257

Mosaic Prophages with Horizontally Acquired Genes Account for the Emergence and Diversification of the Globally Disseminated M1T1 Clone of Streptococcus pyogenes  

PubMed Central

The recrudescence of severe invasive group A streptococcal (GAS) diseases has been associated with relatively few strains, including the M1T1 subclone that has shown an unprecedented global spread and prevalence and high virulence in susceptible hosts. To understand its unusual epidemiology, we aimed to identify unique genomic features that differentiate it from the fully sequenced M1 SF370 strain. We constructed DNA microarrays from an M1T1 shotgun library and, using differential hybridization, we found that both M1 strains are 95% identical and that the 5% unique M1T1 clone sequences more closely resemble sequences found in the M3 strain, which is also associated with severe disease. Careful analysis of these unique sequences revealed three unique prophages that we named M1T1.X, M1T1.Y, and M1T1.Z. While M1T1.Y is similar to phage 370.3 of the M1-SF370 strain, M1T1.X and M1T1.Z are novel and encode the toxins SpeA2 and Sda1, respectively. The genomes of these prophages are highly mosaic, with different segments being related to distinct streptococcal phages, suggesting that GAS phages continue to exchange genetic material. Bioinformatic and phylogenetic analyses revealed a highly conserved open reading frame (ORF) adjacent to the toxins in 18 of the 21 toxin-carrying GAS prophages. We named this ORF paratox, determined its allelic distribution among different phages, and found linkage disequilibrium between particular paratox alleles and specific toxin genes, suggesting that they may move as a single cassette. Based on the conservation of paratox and other genes flanking the toxins, we propose a recombination-based model for toxin dissemination among prophages. We also provide evidence that a minor population of the M1T1 clonal isolates have exchanged their virulence module on phage M1T1.Y, replacing it with a different module identical to that found on a related M3 phage. Taken together, the data demonstrate that mosaicism of the GAS prophages has contributed to the emergence and diversification of the M1T1 subclone.

Aziz, Ramy K.; Edwards, Robert A.; Taylor, William W.; Low, Donald E.; McGeer, Allison; Kotb, Malak

2005-01-01

258

Colonization with antibiotic-resistant Streptococcus pneumoniae in children with sickle cell disease  

Microsoft Academic Search

OBJECTIVE: Because of a susceptibility to severe pneumococcal infection, children with sickle cell disease (SCD) routinely receive penicillin prophylaxis. Increasing rates of penicillin resistance have been reported throughout the world. Our objective was to assess the prevalence of nasopharyngeal colonization with Streptococcus pneumoniae and to assess the antimicrobial susceptibility of the organisms in children with SCD. STUDY DESIGN: Nasopharyngeal cultures

Russell W. Steele; Rajasekharan Warrier; Patrick J. Unkel; Bertrand J. Foch; Richard F. Howes; Sanjay Shah; Karen Williams; Sheila Moore; Sue J. Jue

1996-01-01

259

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

Microsoft Academic Search

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

Ori Elkayam; Jacob Ablin; Dan Caspi

2007-01-01

260

Arcanobacterium pyogenes : molecular pathogenesis of an animal opportunist  

Microsoft Academic Search

Arcanobacterium pyogenes is a commensal and an opportunistic pathogen of economically important livestock, causing diseases as diverse as mastitis, liver abscessation and pneumonia. This organism possesses a number of virulence factors that contribute to its pathogenic potential. A. pyogenes expresses a cholesterol-dependent cytolysin, pyolysin, which is a haemolysin and is cytolytic for immune cells, including macrophages. Expression of pyolysin is

B. Helen Jost; Stephen J. Billington

2005-01-01

261

Identification of a High-Virulence Clone of Type III Streptococcus agalactiae (Group B Streptococcus) Causing Invasive Neonatal Disease  

Microsoft Academic Search

Chromosomal genotypes of 128 isolates of six serotypes (Ia, Ib, Ic, II, Ic\\/II, and III) of Streptococcus agalactiae (group B Streptococcus) recovered predominantly from human infants in the United States were characterized by an analysis of electrophoretically demonstrable allelic profiles at 11 metabolic enzyme loci. Nineteen distinctive electrophoretic types (ETs), representing multilocus clonal genotypes, were identified. Mean genetic diversity per

James M. Musser; Stephen J. Mattingly; Roland Quentin; Alain Goudeau; Robert K. Selander

1989-01-01

262

Post streptococcal acute glomerulonephritis secondary to sporadic Streptococcus equi infection.  

PubMed

Streptococcus equi subspecies zooepidemicus infection is rare in humans, but a well-known cause of pyogenic disease in cows and horses. S. zooepidemicus uncommonly causes post-strep glomerulonephritis (PSGN) in humans via epidemic outbreaks. We present a sporadic case of post S. zooepidemicus glomerulonephritis in a child most probably contracted from a horse. The 14-year-old girl presented with the typical signs of PSGN, with S. equi zooepidemicus isolated from a blood culture, together with a low C3 and raised anti-DNAse B. This is the first known report of a sporadic case of PSGN in a child caused by this organism. PMID:17109135

Thorley, Anna M; Campbell, David; Moghal, Nadeem E; Hudson, Sue

2006-11-16

263

Characterisation of cell wall proteins, virulence factor maturation and invasive disease trigger of Group A Steptococcus  

Microsoft Academic Search

Streptococcus pyogenes (group A Streptococcus; GAS) is a Gram-positive human pathogen responsible for numerous life-threatening diseases, including necrotising fasciitis and streptococcal toxic shock syndrome (STSS). The non-suppurative sequelae of acute rhematic fever (ARF) and acute post-streptococcal glomerulonephritis (APSGN) may develop upon repeated exposure to GAS. Over the last two decades, there has been a world-wide resurgence in GAS infection. In

Jason Nicklaus Cole

2006-01-01

264

Streptococcus pneumoniae: description of the pathogen, disease epidemiology, treatment, and prevention.  

PubMed

Streptococcus pneumoniae causes significant morbidity and mortality. Children younger than 2 years and individuals older than 65 years experience the highest rates of pneumococcal disease. Efforts to treat pneumococcal disease have been complicated by increasing resistance to antimicrobials. Prevention efforts have included the pneumococcal polysaccharide vaccines and the pneumococcal conjugate vaccines, with use of these vaccines targeted to those at highest risk for disease. Information and background on S. pneumoniae and pneumococcal disease are provided. Vaccines targeted at this pathogen are reviewed, and the clinical trials that evaluated their safety, efficacy, and effectiveness are summarized. Also provided are recommendations for use of these vaccines. PMID:16164394

Bridy-Pappas, Angela E; Margolis, Marya B; Center, Kimberly J; Isaacman, Daniel J

2005-09-01

265

Advances in potential M-protein peptide-based vaccines for preventing rheumatic fever and rheumatic heart disease  

Microsoft Academic Search

Rheumatic fever (RF) and rheumatic heart disease (RHD) are post-infectious complications of an infection (or repeated infection)\\u000a with the Gram-positive bacterium Streptococcus pyogenes (also known as group A streptococcus, GAS). RF and RHD are global problems and affect many indigenous populations of developed\\u000a countries and many developing countries. However, RF and RHD are only part of a larger spectrum of

Michael R. Batzloff; Manisha Pandey; Colleen Olive; Michael F. Good

2006-01-01

266

Rheumatic Fever and Rheumatic Heart Disease: Cellular Mechanisms Leading Autoimmune Reactivity and Disease  

Microsoft Academic Search

Introduction  Rheumatic fever (RF) is an autoimmune disease caused by the gram-positive bacteria Streptococcus pyogenes that follows a nontreated throat infection in susceptible children. The disease manifests as polyarthritis, carditis, chorea,\\u000a erythema marginatum, and\\/or subcutaneous nodules. Carditis, the most serious complication, occurs in 30% to 45% of RF patients\\u000a and leads to chronic rheumatic heart disease (RHD), which is characterized by

Luiza Guilherme; Jorge Kalil

2010-01-01

267

Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens  

PubMed Central

The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

Paillot, Romain; Steward, Karen F.; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie C.; Holroyd, Nancy E.; Mungall, Karen; Quail, Michael A.; Sanders, Mandy; Simmonds, Mark; Willey, David; Brooks, Karen; Aanensen, David M.; Spratt, Brian G.; Jolley, Keith A.; Maiden, Martin C. J.; Kehoe, Michael; Chanter, Neil; Bentley, Stephen D.; Robinson, Carl; Maskell, Duncan J.; Parkhill, Julian; Waller, Andrew S.

2009-01-01

268

The economic costs of Group B Streptococcus (GBS) disease: prospective cohort study of infants with GBS disease in England  

Microsoft Academic Search

The objective of this study was to estimate the economic costs over the first 2 years of life of Group B Streptococcus (GBS)\\u000a disease occurring in infants less than 90 days of age. A cost analysis was conducted using a prospective cohort of children\\u000a born between 2000 and 2003 in the Greater London, Oxford, Portsmouth and Bristol areas of England. Unit costs

Elizabeth-Ann Schroeder; Stavros Petrou; Gail Balfour; Oya Edamma; Paul T. Heath

2009-01-01

269

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

PubMed Central

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.

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

2007-01-01

270

Primary pituitary abscess with coexisting pyogenic meningitis: an unexpected diagnosis.  

PubMed

Primary pituitary abscess is a very rare disease most likely associated with pyogenic infection. A 27-year-old woman was initially diagnosed and treated as a case of acute pyogenic meningitis. In view of persistent headache, impaired visual fields, galactorrhea and menstrual irregularities, she underwent evaluation of pituitary mass lesion. Magnetic resonance imaging of the pituitary reported the mass as pituitary macroadenoma. However, transsphenoidal surgery revealed copious collection of purulent materials confirmed as pyogenic pituitary abscess. A follow-up magnetic resonance imaging of the pituitary 2 years later confirmed secondary empty sella. She has developed panhypopituitarism; she remains on appropriate anterior pituitary hormone replacement. PMID:23262813

Bangera, Sachin; Chattopadhyay; Singh, Ranjit Kumar; Al Asousi, Adnan Ali; Joseph, Elizabeth

2013-01-01

271

Neutrophil-potentiating factors released from stimulated lymphocytes; special reference to the increase in neutrophil-potentiating factors from streptococcus-stimulated lymphocytes of patients with Beh?et's disease.  

PubMed Central

The potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130 degrees C, but was not affected by acid treatment at pH 2 or heat treatment at 56 degrees C for 60 min. Its activity was almost not affected by antisera against human interleukin-1, interleukin-2, interferon-gamma or tumour necrosis factor. With the stimulation of T cell mitogens, the supernatants released from the lymphocytes of not only the patients with Behçet's disease but also healthy and diseased controls enhanced neutrophil functions. However, supernatants from streptococcal preparation-stimulated lymphocytes from patients with Behçet's disease had a higher potentiating effect on neutrophil functions. Our study suggests that the enhanced neutrophil functions in patients with Behçet's disease may be related to an abnormally high level of circulating activated T cells in these patients.

Niwa, Y; Mizushima, Y

1990-01-01

272

Pyogenic Sacroiliitis in Children: Two Case Reports  

PubMed Central

Pyogenic sacroiliitis is rare and accounts for approximately 1-2% of osteoarticular infections in children. Considerable delay between presentation and diagnosis is recognized. Two cases of pyogenic sacroiliitis are described. The first case is a 28-month-old girl presented with acute onset of fever, pain in the left hip, and limpness. Computed tomography (CT), bone scans, and magnetic resonance imaging (MRI) of the pelvis showed characteristic findings of infectious sacroiliitis, and blood cultures were negatives. The second case is a 13-year-old girl presented with acute onset of fever, pain in the right hip, and buttock, with inability to walk. The diagnosis of pyogenic sacroiliitis was confirmed by bone scans, and CT of the pelvis and blood cultures have identified Proteus mirabilis. The two children recovered fully after 6 weeks of antimicrobial therapy. Pyogenic sacroiliitis is an uncommon disease in children. The key to successful management is early diagnosis in which CT, bone scans, and MRI findings play a crucial role. If the diagnosis is established promptly, most patients can be managed successfully with antimicrobial therapy.

Ghedira Besbes, L.; Haddad, S.; Abid, A.; Ben Meriem, Ch.; Gueddiche, M. N.

2012-01-01

273

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

PubMed

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

Elkayam, Ori; Ablin, Jacob; Caspi, Dan

2006-10-04

274

Pyogenic meningitis in Ahmedabad.  

PubMed

One hundred and thirty five cerebrospinal fluid (CSF) samples from children clinically diagnosed Pyogenic meningitis (in and around Ahmedabad) were subjected to physical, bacteriological, cytological and biochemical examinations. It was found that all CSF specimens were turbid, the culture positivity varied form 12.12 to 56%. The highest percentage was found in children of less than one year of age. The average percentage of culture positivity was 28.68%. The result of gram stain was more than that of cultural examination. Gram stain of CSF was specific, accurate and highly valuable in the diagnosis of pyogenic meningitis. Among gram positive organisms isolated, Staphylococcus aureus was highest (8.8%) followed by Diplococcus pneumoniae (3.7%), but Klebsiella was predominant (6.6%) among gram negative bacilli. Staph. aureus was 100% sensitive to erythromycin, gentamycin, kanamycin and ampicillin. The results of cytological and biochemical tests correlated (67.1%). There was increase in polymorphs and protein, sugar levels decreased. PMID:8157337

Panjarathinam, R; Shah, R K

275

Isolation and characterization of Streptococcus sp. from diseased flounder (Paralichthys olivaceus) in Jeju Island  

PubMed Central

Streptococcus sp. is gram-positive coccus that causes streptococcal infections in fish due to intensification of aquaculture and caused significant economic losses in fish farm industry. A streptococcal infection occurred from cultured diseased olive flounder (Paralichthys olivaceus) in May, 2005 at a fish farm in Jeju Island, Korea. The diseased flounder exhibited bilateral exophthalmic eyes and rotten gills; water temperature was 16~18? when samples were collected. Of the 22 fish samples collected, 3 samples were identified as Lactococcus garvieae and 18 samples were identified as Streptococcus parauberis by culture-based, biochemical test. Serological methods such as slide agglutination, hemolysis and antimicrobial susceptibility test were also used as well as multiplex PCR-based method to simultaneously detect and confirm the pathogens involved in the infection. S. parauberis and L. garvieae have a target region of 700 and 1100 bp., respectively. One fish sample was not identified because of the difference in the different biochemical and serological tests and was negative in PCR assay. In the present study, it showed that S. parauberis was the dominant species that caused streptococcosis in the cultured diseased flounder.

Baeck, Gun Wook; Kim, Ji Hyung; Gomez, Dennis Kaw

2006-01-01

276

Genetic Characterization of Streptococcus iniae in Diseased Farmed Rainbow Trout (Onchorhynchus mykiss) in Iran  

PubMed Central

Genetic characterization of strains of Streptococcus iniae recovered from morbidity and mortality of farmed rainbow trout in different provinces of Iran were studied. The Gram-positive cocci isolates were obtained from the kidney tissues of diseased rainbow trout on blood agar at 25°C for 72?h. The grown bacteria were then characterized using biochemical and molecular works. The identified 26 isolates of S. iniae producing a 513?bp in PCR procedure were then compared using random amplified polymorphic DNA (RAPD) analysis using 9 random primers. The phylogenetic tree of the RAPD product using UPMGA software included these strains in one genetic group but into two clusters. The results of this study show that S. iniae strains from the diseased rainbow trout in the north part of Iran are genetically similar to those strains in the south and west parts of the country.

Erfanmanesh, A.; Soltani, M.; Pirali, E.; Mohammadian, S.; Taherimirghaed, A.

2012-01-01

277

Prevention of neonatal group B streptococcus disease in the 21st century.  

PubMed

There have been significant reductions in early-onset neonatal group B streptococcus (GBS) disease following implementation of maternal intrapartum antibiotic prophylaxis (IAP) policies. Nevertheless, GBS remains a leading cause of neonatal sepsis in Australia and New Zealand resulting in considerable morbidity and mortality, particularly among preterm infants. In the United States, the universal screening-based approach for identifying women for IAP results in apparently lower rates of early-onset neonatal GBS infection than risk-based assessment. In addition, IAP has altered the profile of newborn infants who develop early-onset disease. Many affected infants lack the typical intrapartum risk factors for GBS infection, are born to mothers with a negative GBS screen or represent missed opportunities for prevention. Clinicians should remain alert for signs of sepsis in any newborn infant. We provide an update of GBS preventative management strategies in the perinatal period taking into account recent United States, Australian and New Zealand guidelines. PMID:22151082

Clifford, Vanessa; Garland, Suzanne M; Grimwood, Keith

2011-12-13

278

Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis of Streptococcus iniae Disease  

Microsoft Academic Search

Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model. The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J.

Jeffrey D. Fuller; Alvin C. Camus; Carla L. Duncan; Victor Nizet; Darrin J. Bast; Ronald L. Thune; Donald E. Low; J. C. S. de Azavedo

2002-01-01

279

Comparison of Streptococcus pneumoniae serotypes causing acute otitis media & invasive disease in young children in the Czech Republic  

Microsoft Academic Search

Background & objectives: The availability of a type-specific pneumococcal vaccine for children is a worldwide problem. It is necessary to study the serotypes prevalent in a country before introducing a type-specific vaccine. The objective of the present study was to analyse the prevalence of Streptococcus pneumoniae serotypes in children suffering from acute otitis media or invasive pneumococcal disease and to

R. Prymula; J. Motlova; P. Kriz

280

[Necrotizing subcutaneous infection by Streptococcus agalactiae].  

PubMed

Necrotizing soft tissue infections constitute some of the most potentially threatening infections that may be acquired in the community or in the hospital milieu as they are associated with a high mortality rate. In most cases they are produced by Streptococcus pyogenes. We report a case of a necrotizing soft tissue infection caused by Streptococcus agalactiae (group B beta hemolytic streptococcus) that involved the leg of an elderly man with chronic lymphatic leukemia and diabetes mellitus. The lesions notably improved after initiating intravenous antibiotic treatment with amoxicillin-clavunate and clindamycin. PMID:17173826

Martín, J M; Molina, I; Ramón, D; Monteagudo, C; Alonso, V; Jordá, E

2006-12-01

281

Comparative genomics and the role of lateral gene transfer in the evolution of bovine adapted Streptococcus agalactiae  

PubMed Central

In addition to causing severe invasive infections in humans, Streptococcus agalactiae, or group B Streptococcus (GBS), is also a major cause of bovine mastitis. Here we provide the first genome sequence for S. agalactiae isolated from a cow diagnosed with clinical mastitis (strain FSL S3-026). Comparison to eight S. agalactiae genomes obtained from human disease isolates revealed 183 genes specific to the bovine strain. Subsequent polymerase chain reaction (PCR) screening for the presence/absence of a subset of these loci in additional bovine and human strains revealed strong differentiation between the two groups (Fisher exact test: p < 0.0001). The majority of the bovine strain-specific genes (~85%) clustered tightly into eight genomic islands, suggesting these genes were acquired through lateral gene transfer (LGT). This bovine GBS also contained an unusually high proportion of insertion sequences (4.3% of the total genome), suggesting frequent genomic rearrangement. Comparison to other mastitis-causing species of bacteria provided strong evidence for two cases of interspecies LGT within the shared bovine environment: bovine S. agalactiae with Streptococcus uberis (nisin U operon) and Streptococcus dysgalactiae subsp. dysgalactiae (lactose operon). We also found evidence for LGT, involving the salivaricin operon, between the bovine S. agalactiae strain and either Streptococcus pyogenes or Streptococcus salivarius. Our findings provide insight intomechanismsfacilitatingenvironmentaladaptationandacquisitionofpotential virulence factors, while highlighting both the key role LGT has played in the recent evolution of the bovine S. agalactiae strain, and the importance of LGT among pathogens within a shared environment.

Richards, Vincent P.; Lang, Ping; Pavinski Bitar, Paulina D.; Lefebure, Tristan; Schukken, Ynte H.; Zadoks, Ruth N.; Stanhope, Michael J.

2011-01-01

282

Penicillin and cephalosporin-resistant strains of Streptococcus pneumoniae causing sepsis and meningitis in children with sickle cell disease  

Microsoft Academic Search

Objective: We investigated the possibility that antimicrobial-resistant pneumococci were causing invasive disease in children with sickle-cell disease (SCD). Study design: Records of all children with SCD observed at the Mid-South Sickle Cell Center (MSSCC) at LeBonheur Children's Medical Center were reviewed from January 1990 to June 1994. Children with SCD and pneumococcal sepsis were identified. The Streptococcus pneumoniae isolates from

P. Joan Chesney; Judith A. Wilimas; Gerald Presbury; Seema Abbasi; Robert J. Leggiadro; Yvonne Davis; Sara W. Day; Gordon E. Schutze; Winfred C. Wang

1995-01-01

283

Mode of action of a lysostaphin-like bacteriolytic agent produced by Streptococcus zooepidemicus 4881.  

PubMed Central

Electron microscopy of zoocin A-treated sensitive streptococcus cells revealed cytoplasmic disruption and ultimately complete rupture of the cell wall. Culture viability and optical density were shown to decrease rapidly and simultaneously in Streptococcus pyogenes FF22 but less quickly in the relatively more resistant Streptococcus mutans 10449. Zoocin A was shown to cleave hexaglycine in a colorimetric cell-free microtiter assay system, and it is concluded that the killing action of zoocin A, like that of lysostaphin, is most probably the result of direct cleavage of the peptidoglycan cross-links in the cell wall. The relationship between sensitivity to zoocin A and the peptidoglycan cross-linkage structure of Streptococcus zooepidemicus, Lactococcus spp., S. pyogenes, Streptococcus gordonii, Streptococcus oralis, S. mutans, and Streptococcus rattus has been evaluated.

Simmonds, R S; Pearson, L; Kennedy, R C; Tagg, J R

1996-01-01

284

Streptococcus pneumoniae in Urinary Tracts of Children with Chronic Kidney Disease  

PubMed Central

Streptococcus pneumoniae is not commonly considered an agent of urinary tract infections. We report 3 children with urinary tract abnormalities who had high numbers of S. pneumoniae in their urine (>104 CFU/mL) and varying clinical symptoms.

Zimmermann, Stefan

2011-01-01

285

Trigger for group A streptococcal M1T1 invasive disease  

Microsoft Academic Search

The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of highly invasive human diseases. The transition from local to systemic infection occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known to express significantly less cysteine protease SpeB than M1T1 isolates from local infections. Here, we show that in comparison to the M1T1 strain 5448, the isogenic

Jason N. Cole; Jason D. McArthur; Fiona C. McKay; Martina L. Sanderson-Smith; Amanda J. Cork; Marie Ranson; Manfred Rohde; Andreas Itzek; Hongmin Sun; David Ginsburg; Malak Kotb; Victor Nizet; G. S. Chhatwal; Mark J. Walker

2006-01-01

286

Streptococcus pneumoniae in Biofilms Are Unable to Cause Invasive Disease Due to Altered Virulence Determinant Production  

PubMed Central

It is unclear whether Streptococcus pneumoniae in biofilms are virulent and contribute to development of invasive pneumococcal disease (IPD). Using electron microscopy we confirmed the development of mature pneumococcal biofilms in a continuous-flow-through line model and determined that biofilm formation occurred in discrete stages with mature biofilms composed primarily of dead pneumococci. Challenge of mice with equal colony forming units of biofilm and planktonic pneumococci determined that biofilm bacteria were highly attenuated for invasive disease but not nasopharyngeal colonization. Biofilm pneumococci of numerous serotypes were hyper-adhesive and bound to A549 type II pneumocytes and Detroit 562 pharyngeal epithelial cells at levels 2 to 11-fold greater than planktonic counterparts. Using genomic microarrays we examined the pneumococcal transcriptome and determined that during biofilm formation S. pneumoniae down-regulated genes involved in protein synthesis, energy production, metabolism, capsular polysaccharide (CPS) production, and virulence. We confirmed these changes by measuring CPS by ELISA and immunoblotting for the toxin pneumolysin and the bacterial adhesins phosphorylcholine (ChoP), choline-binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP). We conclude that biofilm pneumococci were avirulent due to reduced CPS and pneumolysin production along with increased ChoP, which is known to bind C-reactive protein and is opsonizing. Likewise, biofilm pneumococci were hyper-adhesive due to selection for the transparent phase variant, reduced CPS, and enhanced production of PsrP, CbpA, and ChoP. These studies suggest that biofilms do not directly contribute to development of IPD and may instead confer a quiescent mode of growth during colonization.

Sanchez, Carlos J.; Kumar, Nikhil; Lizcano, Anel; Shivshankar, Pooja; Dunning Hotopp, Julie C.; Jorgensen, James H.; Tettelin, Herve; Orihuela, Carlos J.

2011-01-01

287

Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolates Causing Invasive Diseases from Shenzhen Children's Hospital  

PubMed Central

Objective To provide guidance for clinical disease prevention and treatment, this study examined the epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae (S. pneumoniae) associated with invasive pneumococcal diseases (IPDs) among children less than 14 years of age in Shenzhen, China. Materials and Methods All the clinical strains were isolated from children less than 14 years old from January 2009 to August 2012. The serotypes and antibiotic resistance of strains of S. pneumoniae were determined using the capsular swelling method and the E-test. Results A total of 89 strains were isolated and 87 isolates were included. The five prevailing serotypes were 19F (28.7%), 14 (16.1%), 23F (11.5%), 19A (9.2%) and 6B (6.9%). The most common sequence types (ST) were ST271 (21.8%), ST876 (18.4%), ST320 (8.0%) and ST81 (6.9%) which were mainly related to 19F, 14, 19A and 23F, respectively. The potential coverage by 7-, 10-, and 13-valent pneumococcal conjugate vaccine were 77.0%, 77.0%, and 89.7%, respectively. Among the 87 isolates investigated, 11.5% were resistant to penicillin, and for meningitis isolates, the resistance rate was 100%. Multi-drug resistance (MDR) was exhibited by 49 (56.3%) isolates. Eighty-four isolates were resistance to erythromycin, among which, 56 (66.7%) carried the ermB gene alone and 28 (33.3%) expressed both the ermB and mefA/E genes. Conclusions The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 19A and 6A in Shenzhen. The clinical treatment of IPD needs a higher drug concentration of antibiotics. Continued surveillance of the antimicrobial susceptibility and serotypes distribution of IPD isolates may be necessary.

Ma, Zhuoya; Yao, Kaihu; Yu, Sangjie; Zheng, Yuejie; Yang, Yonghong

2013-01-01

288

Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae  

Microsoft Academic Search

The 2,160,267 bp genome sequence of Streptococcus agalactiae, the leading cause of bacterial sepsis, pneumonia, and meningitis in neonates in the U.S. and Europe, is predicted to encode 2,175 genes. Genome comparisons among S. agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and the other completely sequenced genomes identified genes specific to the streptococci and to S. agalactiae. These in silico analyses, combined

Hervé Tettelin; Vega Masignani; Michael J. Cieslewicz; Jonathan A. Eisen; Scott Peterson; Michael R. Wessels; Ian T. Paulsen; Karen E. Nelson; Immaculada Margarit; Timothy D. Read; Lawrence C. Madoff; Alex M. Wolf; Maureen J. Beanan; Lauren M. Brinkac; Sean C. Daugherty; Robert T. Deboy; A. Scott Durkin; James F. Kolonay; Ramana Madupu; Matthew R. Lewis; Diana Radune; Nadezhda B. Fedorova; David Scanlan; Hoda Khouri; Stephanie Mulligan; Heather A. Carty; Robin T. Cline; Susan E. van Aken; John Gill; Maria Scarselli; Marirosa Mora; Emilia T. Iacobini; Cecilia Brettoni; Giuliano Galli; Massimo Mariani; Filippo Vegni; Domenico Maione; Daniela Rinaudo; Rino Rappuoli; John L. Telford; Dennis L. Kasper; Guido Grandi; Claire M. Fraser

2002-01-01

289

speB gene as a specific genetic marker for early detection of rheumatic heart disease in human.  

PubMed

Streptococcus pyrogenic exotoxin B gene (speB) is chromosomally encoded pyrogenic and cardiotoxic virulence factor of S. pyogenes. Exotoxin B is produced only in a secreted form, as a 40 KD proprotein, which is subsequently processed to 28 KD in the mature form. Streptococcus pyogenes infection in human, causes initially pharyngitis due to inhalation of aerosols emitted by infected persons, develops rheumatic fever which leads to the rheumatic heart disease (damage of heart valves). The available detection methods are bacterial culture, ?-hemolysis, bacitracin sensitivity, hippurate test, phadebact test, CRP (C-reactive protein), ESR and PCR. All these methods are either expensive or non-confirmatory and have some limitations. Available PCR methods take more time and require other test to confirm the disease. Our PCR based detection of Streptococcus pyogenes in human using specific primers of speB gene completes overall analysis in 80 min which is the minimum time reported so far for the confirmation of the disease. Amplicon of 423bp of speB gene can be used as a specific genetic marker as it does not show homology with other organisms for early detection of rheumatic heart disease. Our method is specific virulence gene based which is quick, economical and more sensitive as compared with other methods. PMID:23273191

Kaushal, A; Kumar, D; Khare, S; Kumar, A

2012-12-22

290

Streptococcus pneumoniae in urinary tracts of children with chronic kidney disease.  

PubMed

Streptococcus pneumoniae is not commonly considered an agent of urinary tract infections. We report 3 children with urinary tract abnormalities who had high numbers of S. pneumoniae in their urine (?10? CFU/mL) and varying clinical symptoms. PMID:21192871

Burckhardt, Irene; Zimmermann, Stefan

2011-01-01

291

Pyogenic liver abscess caused by Klebsiella pneumoniae genetic serotype K1 in Japan  

Microsoft Academic Search

Pyogenic liver abscess caused by Klebsiella pneumoniae is an emerging disease worldwide, and we know the serotype K1 strain to be the most virulent strain. We report a Japanese\\u000a case of septic pyogenic liver abscess caused by K. pneumoniae genetic serotype K1. A 60-year old man presented at our hospital in a state of cardiopulmonary arrest. From the patient’s\\u000a chief

Yoshitaka Kohayagawa; Keiko Nakao; Misuzu Ushita; Norio Niino; Masayuki Koshizaki; Yuji Yamamori; Yusuke Tokuyasu; Hiroshi Fukushima

2009-01-01

292

Antibiotic therapy in pyogenic meningitis in paediatric patients.  

PubMed

Objective: To isolate and identify the causative pathogen, antibiotic sensitivity testing and success rate of empirical antibiotic therapy in pyogenic meningitis. Study Design: Analytical study. Place and Duration of Study: The Children's Hospital and Institute of Child Health, Lahore, Pakistan, from March to July 2012. Methodology: The study was performed on 72 culture positive meningitis cases in children less than 15 years of age. This therapy was evaluated by monitoring the patient's clinical picture for 14 - 21 days. The collected data was analyzed by Chi-square test. Results: Seventeen different bacteria were isolated. The most commonly occurring bacteria were coagulase negative Staphylococci (25%), E. coli (12.5%), Klebsiella pneumoniae (8.3%), Streptococcus pneumoniae (8.3%) and Pseudomonas aeruginosa (8.3%). All the bacteria were sensitive to vancomycin (96.7%), meropenem (76.7%), amikacin (75%), ciprofloxacin (65.3%), chloramphenicol (46.5%), ceftazidime (44.2%), cefepime (41.9%), co-amoxiclav (38.0%), oxacillin (34.8%), cefotaxime (21.4%), penicillin (20.7%), ceftriaxone (18.6%), cefuroxime (14%) and ampicillin (6.9%). The combination of sulbactam and cefoperazone showed antimicrobial sensitivity of 81.4%. The success rate of empirical antibiotic therapy was 91.7%. Conclusion: It was found that Gram negative bacteria were the major cause of pyogenic meningitis. Mostly there were resistant strains against all commonly used antibiotics except vancomycin. All empirical antibiotic therapies were found to be most successful. PMID:24112254

Tajdin, Fauzia; Rasheed, Muhammad Adil; Ashraf, Muhammad; Rasheed, Huma; Ejaz, Hasan; Khan, Ghulam Jilany

2013-10-01

293

Extramedullary hematopoiesis in pyogenic granuloma.  

PubMed

Extramedullary hematopoiesis (EMH) suggests the presence of hematopoietic stem cells (HSC) outside bone marrow. EMH has been reported, albeit rarely, in pyogenic granuloma (PG), a polypoid lobular capillary hemangioma. However, statistical data have hitherto been lacking on the actual incidence of EMH in PG. Therefore, we here reviewed 157 consecutive cases using routine diagnostic surgical slides and found unequivocal EMH in 17 (10.8%). This indicates that EMH is a rather common finding in PG, which could thus have strong potential to be an important resource for the study of HSC. PMID:24147429

Waraasawapati, Sakda; Koonmee, Supinda; Kusama, Hiroshi; Kudo, Motoshige

2013-10-18

294

Comparative genomics and the role of lateral gene transfer in the evolution of bovine adapted Streptococcus agalactiae.  

PubMed

In addition to causing severe invasive infections in humans, Streptococcus agalactiae, or group B Streptococcus (GBS), is also a major cause of bovine mastitis. Here we provide the first genome sequence for S. agalactiae isolated from a cow diagnosed with clinical mastitis (strain FSL S3-026). Comparison to eight S. agalactiae genomes obtained from human disease isolates revealed 183 genes specific to the bovine strain. Subsequent polymerase chain reaction (PCR) screening for the presence/absence of a subset of these loci in additional bovine and human strains revealed strong differentiation between the two groups (Fisher exact test: p<0.0001). The majority of the bovine strain-specific genes (? 85%) clustered tightly into eight genomic islands, suggesting these genes were acquired through lateral gene transfer (LGT). This bovine GBS also contained an unusually high proportion of insertion sequences (4.3% of the total genome), suggesting frequent genomic rearrangement. Comparison to other mastitis-causing species of bacteria provided strong evidence for two cases of interspecies LGT within the shared bovine environment: bovine S. agalactiae with Streptococcus uberis (nisin U operon) and Streptococcus dysgalactiae subsp. dysgalactiae (lactose operon). We also found evidence for LGT, involving the salivaricin operon, between the bovine S. agalactiae strain and either Streptococcus pyogenes or Streptococcus salivarius. Our findings provide insight into mechanisms facilitating environmental adaptation and acquisition of potential virulence factors, while highlighting both the key role LGT has played in the recent evolution of the bovine S. agalactiae strain, and the importance of LGT among pathogens within a shared environment. PMID:21536150

Richards, Vincent P; Lang, Ping; Bitar, Paulina D Pavinski; Lefébure, Tristan; Schukken, Ynte H; Zadoks, Ruth N; Stanhope, Michael J

2011-04-22

295

Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis of Streptococcus iniae Disease  

PubMed Central

Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model. The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J. D. Fuller, D. J. Bast, V. Nizet, D. E. Low, and J. C. S. de Azavedo, Infect. Immun. 69:1994-2000, 2001). S. iniae produces a cytolysin that confers a hemolytic phenotype on blood agar media. In this study, we characterized the genomic region responsible for S. iniae cytolysin production and assessed its contribution to virulence. Transposon (Tn917) mutant libraries of commensal and disease-associated S. iniae strains were generated and screened for loss of hemolytic activity. Analysis of two nonhemolytic mutants identified a chromosomal locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag operon for streptolysin S (SLS) biosynthesis. Confirmation that the S. iniae cytolysin is a functional homologue of SLS was achieved by PCR ligation mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS inhibitor trypan blue. SLS-negative sagB mutants were compared to their wild-type S. iniae parent strains in the murine model and in human whole-blood killing assays. These studies demonstrated that S. iniae SLS expression is required for local tissue necrosis but does not contribute to the establishment of bacteremia or to resistance to phagocytic clearance.

Fuller, Jeffrey D.; Camus, Alvin C.; Duncan, Carla L.; Nizet, Victor; Bast, Darrin J.; Thune, Ronald L.; Low, Donald E.; de Azavedo, Joyce C. S.

2002-01-01

296

Identification of a Candidate Streptococcus pneumoniae Core Genome and Regions of Diversity Correlated with Invasive Pneumococcal Disease  

PubMed Central

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice.

Obert, Caroline; Sublett, Jack; Kaushal, Deepak; Hinojosa, Ernesto; Barton, Theresa; Tuomanen, Elaine I.; Orihuela, Carlos J.

2006-01-01

297

Identification of a Candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease.  

PubMed

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice. PMID:16861665

Obert, Caroline; Sublett, Jack; Kaushal, Deepak; Hinojosa, Ernesto; Barton, Theresa; Tuomanen, Elaine I; Orihuela, Carlos J

2006-08-01

298

Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.  

PubMed

Early detection of metastatic infection in patients with Gram-positive bacteremia is important as morbidity and mortality are higher in the presence of these foci, probably due to incomplete eradication of clinically silent foci during initial treatment. We performed a prospective study in 115 patients with Staphylococcus aureus or Streptococcus species bacteremia with at least 1 risk factor for the development of metastatic foci, such as community acquisition, treatment delay, persistently positive blood cultures for >48 hours, and persistent fever >72 hours after initiation of treatment. An intensive search for metastatic infectious foci was performed including ą?F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomography scanning for optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first 2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%) patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. The incidence of metastatic infection was similar in patients with Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms guiding the attending physician in the diagnostic workup were present in only a minority of cases (41%). An unknown portal of entry, treatment delay >48 hours, and the presence of foreign body material were significant risk factors for developing metastatic foci. Mean C-reactive protein levels on admission were significantly higher in patients with metastatic infectious foci (74 vs. 160 mg/L). FDG-PET/CT was the first technique to localize metastatic infectious foci in 35 of 115 (30%) patients. As only a minority of foci were accompanied by guiding signs or symptoms, the number of foci revealed by symptom-guided CT, ultrasound, and magnetic resonance imaging remained low. Mortality tended to be lower in patients without complicated infection compared to those with metastatic foci (16% vs. 25%, respectively). Five of 31 patients (16%) without proven metastatic foci died. In retrospect, 3 of these 5 patients likely had metastatic foci that could not be diagnosed while alive. In patients with Gram-positive bacteremia and a high risk of developing complicated infection, a structured protocol including echocardiography and FDG-PET/CT aimed at detecting metastatic infectious foci can contribute to improved outcome. PMID:22391470

Vos, Fidel J; Kullberg, Bart Jan; Sturm, Patrick D; Krabbe, Paul F M; van Dijk, Arie P J; Wanten, Geert J A; Oyen, Wim J G; Bleeker-Rovers, Chantal P

2012-03-01

299

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

PubMed Central

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.

Cellucci, Michael; Simon, Erin; Eppes, Stephen

2012-01-01

300

Rapid Identification of Group A Streptococcus as the Cause of Necrotizing Fasciitis  

Microsoft Academic Search

Group A ?-hemolytic Streptococcus pyogenes (GAS) causes a spectrum of highly aggressive, invasive infections. We report two cases of necrotizing fasciitis in which GAS was identified as the presumptive causative organism with the use of the standard rapid streptococcal diagnostic kit. We believe the rapid test kits may be a useful adjunct in the diagnosis and treatment of this catastrophic

Mark J Ault; Joel Geiderman; Richard Sokolov

1996-01-01

301

Experimental colonization of piglets and gilts with systemic strains of Haemophilus parasuis and Streptococcus suis to prevent disease.  

PubMed Central

Haemophilus parasuis and Streptococcus suis are both major causes of losses during the nursery period, especially in herds using the segregated early weaning system. In this system, only a few piglets may be colonized with the herd's prevalent systemic strain, which results in infection of naive penmates late in the nursery. In view of these factors, the objectives of this study were: (1) to evaluate the early colonization of piglets with the farm's prevalent systemic strain of H. parasuis and S. suis as an alternative method for disease prevention; and (2) to evaluate 2 different protocols for experimental colonization: direct colonization of piglets and colonization of piglets through nose-to-nose contact with inoculated sows. Haemophilus parasuis and S. suis isolates recovered from diseased nursery pigs were characterized by the rep-PCR technique and the herd's prevalent strains were used for colonization. Piglets in the experimentally colonized groups were inoculated at 5 days of age by the oral route using a spray pump. Sows were colonized at 2 weeks prior to farrowing using a similar protocol. Although both colonization protocols were successful in getting the piglets colonized, direct inoculation of 5-day-old piglets with the herd's systemic strains of H. parasuis and S. suis tended to be more effective in reducing the morbidity and the mortality than the colonization of piglets by nose-to-nose contact with inoculated sows. Images Figure 1. Figure 2.

Oliveira, S; Batista, L; Torremorell, M; Pijoan, C

2001-01-01

302

[Susceptibility in parenteral antibiotics in Streptococcus pneumoniae isolated from children with invasive pneumococcal disease].  

PubMed

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of commonly used clinical antimicrobial drugs were examined for 76 strains of Streptococcus pneumoniae isolated between 2006 and 2011 from pediatric patients with invasive pneumococcal infection. Patients from whom bacterial strains were isolated ranged from 4 months to 6 years old and included 50 infants (65.8%) 1 year old and 10 (13.2%) less than 1 year old, i.e., 79.1% of all patients studied. In diagnosis, 38 (50.0%) had occult bacteremia, 34 (44.7%) pneumonia, 3 (3.9%) meningitis, and 1 (1.3%) sepsis. Infections in all but one case who died of sepsis were treated without sequelae. The most frequent capsular serotype among isolates was 6B (20 strains, 26.3%), followed by 19 F (13 strains, 17.1%) and 14 (9 strains, 11.8%). Serotypes for 55 strains (72.4%) corresponded to those contained in heptavalent pneumococcal conjugate vaccine. In classification by resistance based on mutations in penicillin-binding protein genes, 32 were penicillin-resistant S. pneumoniae (42.1%), 35 penicillin intermediate-resistant S. pneumoniae (46.1%), and 11 penicillin-susceptible S. pneumoniae (11.8%). MIC90/MBC90 of drugs were as follows: ampicillin 4/4 microg/mL, cefotaxime 0.5/0.5 microg/mL, ceftriaxone 1/2 microg/ mL, panipenem 0.125/0.125 microg/mL, meropenem 0.5/0.5 microg/mL, and doripenem 0.25/0.25 microg/mL. PMID:23484371

Sakata, Hiroshi

2013-01-01

303

Pyogenic brain abscess, a 15 year survey  

PubMed Central

Background Brain abscess is a potentially fatal disease. This study assesses clinical aspects of brain abscess in a large hospital cohort. Methods Retrospective review of adult patients with pyogenic brain abscess at Rigshospitalet University Hospital, Denmark between 1994 and 2009. Prognostic factors associated with Glasgow Outcome Score (GOS) (death, severe disability or vegetative state) were assessed by logistic regression. Results 102 patients were included. On admission, only 20% of patients had a triad of fever, headache and nausea, 39% had no fever, 26% had normal CRP and 49% had no leucocytosis. Median delay from symptom onset to antibiotic treatment was 7 days (range 0–97 days). Source of infection was contiguous in 36%, haematogenous in 28%, surgical or traumatic in 9% and unknown in 27% of cases. Abscess location did not accurately predict the portal of entry. 67% were treated by burr hole aspiration, 20% by craniotomy and 13% by antibiotics alone. Median duration of antibiotic treatment was 62 days. No cases of recurrent abscess were observed. At discharge 23% had GOS ?3. The 1-, 3- and 12-month mortality was 11%, 17% and 19%. Adverse outcome was associated with a low GCS at admission, presence of comorbidities and intraventricular rupture of abscess. Conclusions The clinical signs of brain abscess are unspecific, many patients presented without clear signs of infection and diagnosis and treatment were often delayed. Decreased GCS, presence of comorbidities and intraventricular rupture of brain abscess were associated with poor outcome. Brain abscess remains associated with considerable morbidity and mortality.

2012-01-01

304

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

PubMed Central

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.

Rhee, Hanna; Cameron, Daniel J

2012-01-01

305

Developing oral probiotics from Streptococcus salivarius.  

PubMed

Considerable human illness can be linked to the development of oral microbiota disequilibria. The predominant oral cavity commensal, Streptococcus salivarius has emerged as an important source of safe and efficacious probiotics, capable of fostering more balanced, health-associated oral microbiota. Strain K12, the prototype S. salivarius probiotic, originally introduced to counter Streptococcus pyogenes infections, now has an expanded repertoire of health-promoting applications. K12 and several more recently proposed S. salivarius probiotics are now being applied to control diverse bacterial consortia infections including otitis media, halitosis and dental caries. Other potential applications include upregulation of immunological defenses against respiratory viral infections and treatment of oral candidosis. An overview of the key steps required for probiotic development is also presented. PMID:23231486

Wescombe, Philip A; Hale, John D F; Heng, Nicholas C K; Tagg, John R

2012-12-01

306

Disease Isolates of Streptococcus pseudopneumoniae and Non-Typeable S. pneumoniae Presumptively Identified as Atypical S. pneumoniae in Spain  

PubMed Central

We aimed to obtain insights on the nature of a collection of isolates presumptively identified as atypical Streptococcus pneumoniae recovered from invasive and non-invasive infections in Spain. One-hundred and thirty-two isolates were characterized by: optochin susceptibility in ambient and CO2-enriched atmosphere; bile solubility; PCR-based assays targeting pneumococcal genes lytA, ply, pspA, cpsA, Spn9802, aliB-like ORF2, and a specific 16S rRNA region; multilocus sequence analysis; and antimicrobial susceptibility. By multilocus sequence analysis, 61 isolates were S. pseudopneumoniae, 34 were pneumococci, 13 were S. mitis, and 24 remained unclassified as non-pneumococci. Among S. pseudopneumoniae isolates, 51 (83.6%) were collected from respiratory tract samples; eight isolates were obtained from sterile sources. High frequency of non-susceptibility to penicillin (60.7%) and erythromycin (42.6%) was found. Only 50.8% of the S. pseudopneumoniae isolates displayed the typical optochin phenotype originally described for this species. None harbored the cpsA gene or the pneumococcal typical lytA restriction fragment length polymorphism. The Spn9802 and the specific 16S rRNA regions were detected among the majority of the S. pseudopneumoniae isolates (n?=?59 and n?=?49, respectively). The ply and pspA genes were rarely found. A high genetic diversity was found and 59 profiles were identified. Among the S. pneumoniae, 23 were capsulated and 11 were non-typeable. Three non-typeable isolates, associated to international non-capsulated lineages, were recovered from invasive disease sources. In conclusion, half of the atypical pneumococcal clinical isolates were, in fact, S. pseudopneumoniae and one-fourth were other streptococci. We identified S. pseudopneumoniae and non-typeable pneumococci as cause of disease in Spain including invasive disease.

Fenoll, Asuncion; Linares, Josefina; de Lencastre, Herminia; Ardanuy, Carmen; Sa-Leao, Raquel

2013-01-01

307

Pyogenic granuloma of the gingiva: A misnomer? - A case report and review of literature  

PubMed Central

Pyogenic granuloma is a commonly occurring inflammatory hyperplasia of the skin and oral mucosa. It is not associated with pus as its name suggests and histologically it resembles an angiomatous lesion rather than a granulomatous lesion. It is known by a variety of names such as Crocker and Hartzell's disease, granuloma pyogenicum, granuloma pediculatum benignum, benign vascular tumor and during pregnancy as granuloma gravidarum. This tumor like growth is considered to be non-neoplastic in nature and it presents itself in the oral cavity in various clinical and histological forms. Due to its frequent occurrence in the oral cavity, especially the gingiva, this article presents a case report of a large pyogenic granuloma of the gingiva and its management, reviews the literature and discusses why the term “pyogenic granuloma” is a misnomer.

Gomes, Sheiba R.; Shakir, Quaid Johar; Thaker, Prarthana V.; Tavadia, Jamshed K.

2013-01-01

308

Pyogenic granuloma of the gingiva: A misnomer? - A case report and review of literature.  

PubMed

Pyogenic granuloma is a commonly occurring inflammatory hyperplasia of the skin and oral mucosa. It is not associated with pus as its name suggests and histologically it resembles an angiomatous lesion rather than a granulomatous lesion. It is known by a variety of names such as Crocker and Hartzell's disease, granuloma pyogenicum, granuloma pediculatum benignum, benign vascular tumor and during pregnancy as granuloma gravidarum. This tumor like growth is considered to be non-neoplastic in nature and it presents itself in the oral cavity in various clinical and histological forms. Due to its frequent occurrence in the oral cavity, especially the gingiva, this article presents a case report of a large pyogenic granuloma of the gingiva and its management, reviews the literature and discusses why the term "pyogenic granuloma" is a misnomer. PMID:24174735

Gomes, Sheiba R; Shakir, Quaid Johar; Thaker, Prarthana V; Tavadia, Jamshed K

2013-07-01

309

Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus Strain Causing Epidemic Nephritis: New Information about an Old Disease  

PubMed Central

Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis.

Beres, Stephen B.; Sesso, Ricardo; Pinto, Sergio Wyton L.; Hoe, Nancy P.; Porcella, Stephen F.; DeLeo, Frank R.; Musser, James M.

2008-01-01

310

Identification of ?-haemolysin-encoding genes in Streptococcus anginosus.  

PubMed

Streptococcus anginosus is an emerging pathogen, but little is known about its virulence factors. To detect the genes responsible for ?-haemolysis we performed genomic mutagenesis of the ?-haemolytic S. anginosus type strain ATCC 12395 using the vector pGhost9:ISS1. Integration site analysis of 15 non-haemolytic mutants identified a gene cluster with high homology to the genes of the streptolysin S (SLS) encoding sag gene cluster of S. pyogenes. The gene cluster harbours 10 open reading frames displaying significant similarities to the S. pyogenes genes sagA-sagI, with the identities on protein level ranging from 38 to 87%. Complementation assays of S. anginosus sagB and sagD integration mutants with the respective genes confirmed their importance for ?-haemolysin production and suggest the presence of post-translational modifications in S. anginosus SLS similar to SLS of S. pyogenes. Characterization of the S. anginosus haemolysin in comparison to the S. pyogenes SLS showed that the haemolysin is surface bound, but in contrast to S. pyogenes neither fetal calf serum nor RNA was able to stabilize the haemolysin of S. anginosus in culture supernatants. Inhibition of ?-haemolysis by polyethylene glycol of different sizes was carried out, giving no evidence of a pore-forming haemolytic mechanism. Analysis of a whole genome shotgun sequence of Streptococcus constellatus, a closely related streptococcal species that belongs to the S. anginosus group, revealed a similar sag gene cluster. Employing a genomic mutagenesis strategy we were able to determine an SLS encoding gene cluster in S. anginosus and demonstrate its importance for ?-haemolysin production in S. anginosus. PMID:23594064

Asam, D; Mauerer, S; Walheim, E; Spellerberg, B

2013-04-18

311

Urinary bladder pyogenic granuloma: a case report  

PubMed Central

Introduction Although more than 100 cases of hemangioma of the urinary bladder have been reported, capillary-type hemangiomas of the bladder are rare. Pyogenic granulomas, which are common tumor-like vascular lesions of the skin and oral mucous membranes, reveal histopathological findings similar to capillary-type hemangiomas and are differentiated from ordinary hemangiomas by clinical features and etiologic factors. Little is known regarding the occurrence of pyogenic granulomas in the urinary bladder. Case presentation We present the case of a 78-year-old Japanese man who had developed a hemangiomatous lesion in his bladder which led to acute clot retention. He had a recent history of chemotherapy for pancreatic cancer. A solitary pedunculated mass measuring 1.2?cm was observed in the bladder. Histopathological analysis of the resected mass revealed marked lobular capillary proliferation with surface erosions. Conclusion Cystoscopic and pathologic findings in addition to possible predisposing factors supported a diagnosis of pyogenic granuloma of the urinary bladder.

2012-01-01

312

Outbreak of Group A beta hemolytic Streptococcus pharyngitis in a Peruvian military facility, April 2012.  

PubMed

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a common cause of acute pharyngitis as well as other diseases. Closed populations such as those living on military bases, nursing homes, and prisons are particularly vulnerable to GAS outbreaks due to crowding that facilitates person-to-person transmission. This report details a large outbreak of GAS pharyngitis at a Peruvian military training facility near Lima, Peru, in April 2012. Initial findings showed 145 cases. However, as the investigation continued it was revealed that some trainees may have concealed their illness to avoid real or perceived negative consequences of seeking medical care. A subsequent anonymous survey of all trainees revealed at least 383 cases of pharyngitis among the facility's 1,549 trainees and an attack rate of 34 percent among the 1,137 respondents. The epidemic curve revealed a pattern consistent with routine person-to-person transmission, although a point-source initiating event could not be excluded. Laboratory results showed GAS emm type 80.1 to be the culprit pathogen, an organism not commonly implicated in outbreaks of GAS in the Americas. Barious unique and illustrative features of outbreak investigation in military facilities and populations are discussed. PMID:23819536

Ramos, Mariana; Valle, Ruben; Reaves, Eric J; Loayza, Luis; Gonzalez, Sofia; Bernal, Maria; Soto, Giselle; Hawksworth, Anthony W; Kasper, Matthew R; Tilley, Drake H; De Mattos, Carlos A; Brown, Jason R; Bausch, David G

2013-06-01

313

SFS, a Novel Fibronectin-Binding Protein from Streptococcus equi, Inhibits the Binding between Fibronectin and Collagen  

PubMed Central

The obligate parasitic bacterium Streptococcus equi subsp. equi is the causative agent of strangles, a serious disease of the upper respiratory tract in horses. In this study we have, using shotgun phage display, cloned from S. equi subsp. equi and characterized a gene, called sfs, encoding a protein termed SFS, representing a new type of fibronectin (Fn)-binding protein. The sfs gene was found to be present in all 50 isolates of S. equi subsp. equi tested and in 41 of 48 S. equi subsp. zooepidemicus isolates tested. The sfs gene is down-regulated during growth in vitro compared to fnz, a previously characterized gene encoding an Fn-binding protein from S. equi subsp. zooepidemicus. Sequence comparisons revealed no similarities to previously characterized Fn-binding proteins, but high scores were obtained against collagen. Besides similarity due to the high content of glycine, serine, and proline residues present in both proteins, there was a nine-residue motif present both in collagen and in the Fn-binding domain of SFS. By searching the Oklahoma S. pyogenes database, we found that this motif is also present in a potential cell surface protein from S. pyogenes. Protein SFS was found to inhibit the binding between Fn and collagen in a concentration-dependent way.

Lindmark, Hans; Guss, Bengt

1999-01-01

314

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

PubMed Central

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.

1993-01-01

315

?-enolase, a plasmin(ogen) binding and cell wall associating protein from a fish pathogenic Streptococcus iniae strain  

Microsoft Academic Search

The plasmin(ogen) binding property of pathogenic bacteria is suggested to be one of the characteristics that may contribute to tissue invasion. Recently, the presence of a surface-localized ?-enolase that binds both plasmin and plasminogen has been reported from Streptococcus pyogenes and from S. pneumoniae. To investigate whether ?-enolase of S. iniae has similar characteristics to that of the above streptococci,

Min Sun Kim; Seung Hyuk Choi; Eun Hye Lee; Yoon Kwon Nam; Sung Koo Kim; Ki Hong Kim

2007-01-01

316

Pyogenic Flexor Tenosynovitis Associated with Cellulosimicrobium cellulans?  

PubMed Central

Cellulosimicrobium cellulans, formerly known as Oerskovia xanthineolytica, is a rare human pathogen, often in association with a foreign body. A case of pyogenic flexor tenosynovitis associated with C. cellulans in an immunocompetent boy is described, underlining the importance of prompt surgical and microbiologic evaluation.

Tucker, Joseph D.; Montecino, Rafael; Winograd, Jonathan M.; Ferraro, MaryJane; Michelow, Ian C.

2008-01-01

317

Necrotizing fasciitis resulting from human bites: A report of two cases of disease caused by group A streptococcus  

PubMed Central

Necrotizing fasciitis is a serious and potentially life-threatening condition. Although bite wounds are common, they are not frequently reported as a cause of necrotizing fasciitis. In the present article, two cases of bite-associated necrotizing fasciitis caused by group A streptococcus are reported. Previously published cases are also reviewed.

Sikora, Christopher A; Spielman, Jack; MacDonald, Kerry; Tyrrell, Gregory J; Embil, John M

2005-01-01

318

Streptococcus bovis Meningitis in an Infant  

Microsoft Academic Search

Streptococcus bovis is a nonenterococcal, group D streptococcus which has been identified as a causative agent for serious human infections, including endocarditis, bacteremia, and septic arthritis. Several cases of adult S. bovis meningitis have been reported, usually in association with underlying disease. In the neonatal period, it is an uncommon agent of meningitis. We report, to our knowledge, the third

RUSSELL J. GRANT; TERENCE R. WHITEHEAD; JAMES E. ORR; A. O. Fox

2000-01-01

319

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

PubMed Central

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.

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

2008-01-01

320

Getting to Grips with Strangles: An Effective Multi-Component Recombinant Vaccine for the Protection of Horses from Streptococcus equi Infection  

PubMed Central

Streptococcus equi subspecies equi (S. equi) is a clonal, equine host-adapted pathogen of global importance that causes a suppurative lymphodendopathy of the head and neck, more commonly known as Strangles. The disease is highly prevalent, can be severe and is highly contagious. Antibiotic treatment is usually ineffective. Live attenuated vaccine strains of S. equi have shown adverse reactions and they suffer from a short duration of immunity. Thus, a safe and effective vaccine against S. equi is highly desirable. The bacterium shows only limited genetic diversity and an effective vaccine could confer broad protection to horses throughout the world. Welsh mountain ponies (n?=?7) vaccinated with a combination of seven recombinant S. equi proteins were significantly protected from experimental infection by S. equi, resembling the spontaneous disease. Vaccinated horses had significantly reduced incidence of lymph node swelling (p?=?0.0013) lymph node abscessation (p?=?0.00001), fewer days of pyrexia (p?=?0.0001), reduced pathology scoring (p?=?0.005) and lower bacterial recovery from lymph nodes (p?=?0.004) when compared with non-vaccinated horses (n?=?7). Six of 7 vaccinated horses were protected whereas all 7 non-vaccinated became infected. The protective antigens consisted of five surface localized proteins and two IgG endopeptidases. A second vaccination trial (n?=?7+7), in which the IgG endopeptidases were omitted, demonstrated only partial protection against S. equi, highlighting an important role for these vaccine components in establishing a protective immune response. S. equi shares >80% sequence identity with Streptococcus pyogenes. Several of the components utilized here have counterparts in S. pyogenes, suggesting that our findings have broader implications for the prevention of infection with this important human pathogen. This is one of only a few demonstrations of protection from streptococcal infection conferred by a recombinant multi-component subunit vaccine in a natural host.

Guss, Bengt; Flock, Margareta; Frykberg, Lars; Waller, Andrew S.; Robinson, Carl; Smith, Ken C.; Flock, Jan-Ingmar

2009-01-01

321

Getting to grips with strangles: an effective multi-component recombinant vaccine for the protection of horses from Streptococcus equi infection.  

PubMed

Streptococcus equi subspecies equi (S. equi) is a clonal, equine host-adapted pathogen of global importance that causes a suppurative lymphodendopathy of the head and neck, more commonly known as Strangles. The disease is highly prevalent, can be severe and is highly contagious. Antibiotic treatment is usually ineffective. Live attenuated vaccine strains of S. equi have shown adverse reactions and they suffer from a short duration of immunity. Thus, a safe and effective vaccine against S. equi is highly desirable. The bacterium shows only limited genetic diversity and an effective vaccine could confer broad protection to horses throughout the world. Welsh mountain ponies (n = 7) vaccinated with a combination of seven recombinant S. equi proteins were significantly protected from experimental infection by S. equi, resembling the spontaneous disease. Vaccinated horses had significantly reduced incidence of lymph node swelling (p = 0.0013) lymph node abscessation (p = 0.00001), fewer days of pyrexia (p = 0.0001), reduced pathology scoring (p = 0.005) and lower bacterial recovery from lymph nodes (p = 0.004) when compared with non-vaccinated horses (n = 7). Six of 7 vaccinated horses were protected whereas all 7 non-vaccinated became infected. The protective antigens consisted of five surface localized proteins and two IgG endopeptidases. A second vaccination trial (n = 7+7), in which the IgG endopeptidases were omitted, demonstrated only partial protection against S. equi, highlighting an important role for these vaccine components in establishing a protective immune response. S. equi shares >80% sequence identity with Streptococcus pyogenes. Several of the components utilized here have counterparts in S. pyogenes, suggesting that our findings have broader implications for the prevention of infection with this important human pathogen. This is one of only a few demonstrations of protection from streptococcal infection conferred by a recombinant multi-component subunit vaccine in a natural host. PMID:19763180

Guss, Bengt; Flock, Margareta; Frykberg, Lars; Waller, Andrew S; Robinson, Carl; Smith, Ken C; Flock, Jan-Ingmar

2009-09-18

322

Sturge-Weber syndrome with pyogenic granuloma.  

PubMed

Vascular lesions represent one of the rare disorders affecting overall quality of life of a child. A wide variety of these conditions are known, ranging from a simple nevus to life-threatening hemangiomas. These conditions make the treatment options more complex due to the fear of uncontrollable bleeding. The present case is one of the rare combinations of Sturge-Weber syndrome and pyogenic granuloma. Conditions of importance and treatment options keeping hemangioma in mind are discussed. PMID:24124305

Mopagar, Viddyasagar P; Choudhari, Shantanu; Subbaraya, Dwijendra Kocherlakota; Peesapati, Sudha

2013-07-01

323

Sturge-Weber syndrome with pyogenic granuloma  

PubMed Central

Vascular lesions represent one of the rare disorders affecting overall quality of life of a child. A wide variety of these conditions are known, ranging from a simple nevus to life-threatening hemangiomas. These conditions make the treatment options more complex due to the fear of uncontrollable bleeding. The present case is one of the rare combinations of Sturge-Weber syndrome and pyogenic granuloma. Conditions of importance and treatment options keeping hemangioma in mind are discussed.

Mopagar, Viddyasagar P.; Choudhari, Shantanu; Subbaraya, Dwijendra Kocherlakota; Peesapati, Sudha

2013-01-01

324

Differential virulence gene expression of group A Streptococcus serotype M3 in response to co-culture with Moraxella catarrhalis.  

PubMed

Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2 aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (?4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (?4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence. PMID:23626831

Verhaegh, Suzanne J C; Flores, Anthony R; van Belkum, Alex; Musser, James M; Hays, John P

2013-04-23

325

Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis  

PubMed Central

Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2 aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (?4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (?4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence.

Verhaegh, Suzanne J. C.; Flores, Anthony R.; van Belkum, Alex; Musser, James M.; Hays, John P.

2013-01-01

326

Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease.  

PubMed

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-A 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

Kagawa, T F; Cooney, J C; Baker, H M; McSweeney, S; Liu, M; Gubba, S; Musser, J M; Baker, E N

2000-02-29

327

Intra-Abscess Administration of Antibiotics Through Ultrasound-Guided Percutaneous Catheter for the Treatment of Pyogenic Liver Abscess  

PubMed Central

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.

Alvarez-Uria, Gerardo; Pakam, Raghavakalyan; Midde, Manoranjan; Naik, Praveen Kumar

2013-01-01

328

Antimicrobial susceptibility of Arcanobacterium pyogenes isolated from the lungs of white-tailed deer (Odocoileus virginianus) with pneumonia.  

PubMed

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

Tell, Lisa A; Brooks, Jason W; Lintner, Valerie; Matthews, Tammy; Kariyawasam, Subhashinie

2011-09-01

329

Bacteriocin of a Group A Streptococcus: Partial Purification and Properties  

PubMed Central

The production of bacteriocin-like inhibition by certain strains of group A streptococci was demonstrated during the growth of these organisms on solid nutrient media. Active bacteriocin could not be recovered from broth cultures, possibly because of its inactivation by streptococcal proteinase. The bacteriocin, streptocin A, produced by Streptococcus pyogenes strain FF-22 was partially purified by chemical precipitation and chromatography on carboxymethyl-cellulose. Streptocin A inhibited the growth of various gram-positive organisms but none of a wide range of different gram-negative strains. The bacteriocin was inactivated by proteolytic enzymes and, although labile in alkali, it was extremely stable to heating in mild acids. Images

Tagg, J. R.; Read, R. S. D.; McGiven, A. R.

1973-01-01

330

Invasive infection caused by Streptococcus dysgalactiae subsp. equisimilis : characteristics of strains and clinical features  

Microsoft Academic Search

Among clinically isolated ?-hemolytic streptococci, Streptococcus pyogenes and S. agalactiae were considered the main pathogens in humans until recently. In 1996, S. dysgalactiae subsp. equisimilis (SDSE) was proposed as a novel taxon among human-derived streptococcal isolates. SDSE has Lancefield group C or G antigens,\\u000a exhibits strong ?-hemolysis, and exerts streptokinase activity upon human plasminogen and proteolytic activity upon human\\u000a fibrin.

Takashi Takahashi; Kimiko Ubukata; Haruo Watanabe

2011-01-01

331

Molecular epidemiology of group A streptococcus causing scarlet fever in northern Taiwan, 2001–2002  

Microsoft Academic Search

In this study, 830 Streptococcus pyogenes isolates collected between 2001 and 2002 from patients with scarlet fever in northern Taiwan were analyzed by M protein gene (emm) sequence typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. A total of 21 emm types and 56 PFGE patterns were identified. The most frequent emm types were emm1 (29.2%), emm4 (24.1%), emm12

Ying-Yan Chen; Chung-Ter Huang; Shu-Man Yao; Yi-Ching Chang; Pei-Wun Shen; Chen-Ying Chou; Shu-Ying Li

2007-01-01

332

Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome.  

PubMed Central

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.

Johnson, Abdul-Wahab B. R.; Adedoyin, Olanrewaju T.; Abdul-Karim, Aishat A.; Olanrewaju, Abdul-Waheed I.

2007-01-01

333

M-Like Proteins of Streptococcus dysgalactiae  

PubMed Central

Streptococcus dysgalactiae is one of the most important bacterial species isolated from bovine mastitis. To identify potential virulence factors of this species we prepared chromosomal DNA from strain 8215 and constructed a phage display library. By affinity selection of the library against fibrinogen (Fg), we isolated and characterized a gene, called demA, encoding a protein with the molecular mass of ?58 kDa, called DemA, displaying both plasma protein binding properties and sequence similarities with the M and M-like proteins of other streptococcal species. Purified recombinant DemA protein was found to completely inhibit Fg-binding to cells of S. dysgalactiae. A continued sequence analysis revealed that the demA gene was preceded by an open reading frame (dmgA) coding for a putative protein, called DmgA, with high similarities to the Mga proteins of Streptococcus pyogenes. By additional cloning, the corresponding dmgA and demA genes from another strain, called Epi9, were isolated and analyzed. These genes, called dmgB and demB, respectively, revealed a high degree of similarity to the corresponding genes in strain 8215. Increased binding of Fg by cells of strain Epi9, grown in an atmosphere with 10% CO2, was correlated to an enhanced transcription of the demB gene as shown in a Northern blot. Strain 8215 did not respond to CO2, which could be explained by a nonfunctional dmgA gene due to insertion of an insertion sequence element. Based on sequence similarities of the described proteins to Mga, M, and M-like proteins and the response to elevated level of CO2, we suggest that the dmg and dem genes are members of a regulon similar to the described mga regulon in S. pyogenes, which encodes several virulence factors in this species.

Vasi, Jozsef; Frykberg, Lars; Carlsson, Lena E.; Lindberg, Martin; Guss, Bengt

2000-01-01

334

A Second Tylosin Resistance Determinant, Erm B, in Arcanobacterium pyogenes  

Microsoft Academic Search

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.

B. Helen Jost; Hien T. Trinh; J. Glenn Songer; Stephen J. Billington

2004-01-01

335

CT and MR Imaging Features of Pyogenic Ventriculitis  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Pyogenic ventriculitis is an uncommon manifestation of severe intracranial infection that might be clinically obscure. We hypothesized that determining characteristic imaging features of pyogenic ventriculitis in patients with appropriate risk fac- tors might improve recognition of this severe infection. METHODS: Review of the medical records from 1990 to 2000 revealed 17 cases (12 men, five women) that

Melanie B. Fukui; Robert L. Williams; Sanjay Mudigonda

336

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

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.

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

337

In vitro susceptibility of ceftiofur against Streptococcus equi subsp zooepidemicus and subsp equi isolated from horses with lower respiratory disease in Europe since 2002.  

PubMed

In vitro activity of ceftiofur and six other antimicrobial agents was evaluated against 79 Streptococcus equi subsp zooepidemicus isolates collected from horses with respiratory disease in Europe during 2007 and 2008. In addition, the in vitro activity of ceftiofur and other antimicrobial drugs was assessed against 59 S. equi subsp zooepidemicus and 49 S. equi subsp equi isolates collected by veterinary diagnostic laboratories in Europe from 2002 to 2006. The lowest concentration of ceftiofur that inhibited the growth of 90% of the isolates (MIC90) was 0.12 microg/ml, with the Clinical Laboratory Standards Institute-approved susceptible breakpoint set at ? 0.25 microg/ml for ceftiofur against S. equi subsp zooepidemicus. The MIC90 values remained consistent when comparing the isolates collected from diagnostic laboratories or from the field study. PMID:20425729

Bade, Donald; Portis, Ellen; Keane, Caroline; Hallberg, John; Bryson, Lawrence; Sweeney, Mike; Boner, Pamela

2009-01-01

338

Binding of complement regulatory proteins to group A Streptococcus.  

PubMed

Streptococcus pyogenes or Group A Streptococcus (GAS) is the etiologic agent of important human infections such as acute pharyngitis, impetigo, rheumatic fever and the streptococcal toxic shock syndrome. Binding of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), C4b-binding protein (C4BP), or CD46 is a crucial step in the pathogenesis of these infections. M protein is the GAS protein that generally mediates these interactions. However, a detailed analysis of the reports that have investigated the binding of complement regulatory components to GAS indicates that this microorganism has evolved alternative mechanisms for the recruitment of complement regulatory proteins to the bacterial surface. This article summarizes these data to provide a starting point for future research aimed at the characterization of additional mechanisms developed by GAS to evade the immune system. PMID:19388169

Oliver, Maria A; Rojo, José M; Rodríguez de Córdoba, Santiago; Alberti, Sebastián

2008-12-30

339

Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.  

PubMed

To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513

Kong, Il Gyu; Sato, Ayuko; Yuki, Yoshikazu; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari; Kiyono, Hiroshi

2013-03-04

340

Pyogenic liver abscess caused by Klebsiella pneumoniae genetic serotype K1 in Japan.  

PubMed

Pyogenic liver abscess caused by Klebsiella pneumoniae is an emerging disease worldwide, and we know the serotype K1 strain to be the most virulent strain. We report a Japanese case of septic pyogenic liver abscess caused by K. pneumoniae genetic serotype K1. A 60-year old man presented at our hospital in a state of cardiopulmonary arrest. From the patient's chief complaint of chest pain, we suspected acute coronary syndrome, i.e., acute myocardial infarction. We used extracorporeal circulation and checked coronary angiography, but the 75% stenosis by itself could not adequately account for the patient's critical condition. The patient's laboratory data indicated multiple organ failure. The patient's condition did not improve while in intensive care and he died 20 h after the onset of the cardiopulmonary arrest. Pathological autopsy later showed colliquative necrosis in the deltoid and left greater pectoral muscles, as well as liver abscesses. The patient's blood, gastric juice, and stool cultures all grew a Gram-negative bacillus identified as Klebsiella pneumoniae. We also performed capsular polysaccharide synthesis (cps) genotyping by polymerase chain reaction for the detection of K serotype-specific alleles at the wzx and wzy loci. The result indicated that wzx_K1 and wzy_K1 were positive. This is the first reported Japanese case of septic pyogenic liver abscess caused by K. pneumoniae genetic serotype K1. PMID:19688245

Kohayagawa, Yoshitaka; Nakao, Keiko; Ushita, Misuzu; Niino, Norio; Koshizaki, Masayuki; Yamamori, Yuji; Tokuyasu, Yusuke; Fukushima, Hiroshi

2009-08-18

341

Prevention of Group B Streptococcus Early-onset Neonatal Sepsis: Comparison of the Center for Disease Control and Prevention Screening-Based Protocol to a Risk-Based Protocol in Infants at Greater Than 37 Weeks' Gestation  

Microsoft Academic Search

OBJECTIVE: To compare the Center for Disease Control consensus guidelines' screening-based strategy to a risk-based strategy as regards the incidence of early-onset group B streptococcus (GBS) infection among term infants.STUDY DESIGN: A cohort of university hospital prenatal clinic mother–infant pairs who were screened for GBS at 35 to 37 weeks' gestation were compared to a matched control group of unscreened

George J Gilson; Franklyn Christensen; Heather Romero; Kimberley Bekes; Lorena Silva; Clifford R Qualls

2000-01-01

342

Human toxocariasis and pyogenic liver abscess: a possible association  

Microsoft Academic Search

OBJECTIVES:To study the role of human toxocariasis in the pathogenesis of pyogenic liver abscess.METHODS:We compared the serology for toxocariasis and serum levels of IgE in 16 patients with pyogenic liver abscess to those in 32 matched (age and gender) controls to define the possible association between these two entities.RESULTS:The serology for toxocariasis was positive in 10 of 16 patients compared

Abdunnabi A. Rayes; Daniela Teixeira; J. C. Serufo; Vandack Nobre; Carlos M. Antunes; J. R. Lambertucci

2001-01-01

343

Novel Twin Streptolysin S-Like Peptides Encoded in the sag Operon Homologue of Beta-Hemolytic Streptococcus anginosus  

PubMed Central

Streptococcus anginosus is a member of the anginosus group streptococci, which form part of the normal human oral flora. In contrast to the pyogenic group streptococci, our knowledge of the virulence factors of the anginosus group streptococci, including S. anginosus, is not sufficient to allow a clear understanding of the basis of their pathogenicity. Generally, hemolysins are thought to be important virulence factors in streptococcal infections. In the present study, a sag operon homologue was shown to be responsible for beta-hemolysis in S. anginosus strains by random gene knockout. Interestingly, contrary to pyogenic group streptococci, beta-hemolytic S. anginosus was shown to have two tandem sagA homologues, encoding streptolysin S (SLS)-like peptides, in the sag operon homologue. Gene deletion and complementation experiments revealed that both genes were functional, and these SLS-like peptides were essential for beta-hemolysis in beta-hemolytic S. anginosus. Furthermore, the amino acid sequence of these SLS-like peptides differed from that of the typical SLS of S. pyogenes, especially in their propeptide domain, and an amino acid residue indicated to be important for the cytolytic activity of SLS in S. pyogenes was deleted in both S. anginosus homologues. These data suggest that SLS-like peptides encoded by two sagA homologues in beta-hemolytic S. anginosus may be potential virulence factors with a different structure essential for hemolytic activity and/or the maturation process compared to the typical SLS present in pyogenic group streptococci.

Tabata, Atsushi; Nakano, Kota; Ohkura, Kazuto; Tomoyasu, Toshifumi; Kikuchi, Ken; Whiley, Robert A.

2013-01-01

344

Full-genome dissection of an epidemic of severe invasive disease caused by a hypervirulent, recently emerged clone of group A Streptococcus.  

PubMed

Group A Streptococcus (GAS) causes an exceptionally broad range of infections in humans, from relatively mild pharyngitis and skin infections to life-threatening necrotizing fasciitis and toxic shock syndrome. An epidemic of severe invasive human infections caused by type emm59 GAS, heretofore an exceedingly rare cause of disease, spread west to east across Canada over a 3-year period (2006 to 2008). By sequencing the genomes of 601 epidemic, historic, and other emm59 organisms, we discovered that a recently emerged, genetically distinct emm59 clone is responsible for the Canadian epidemic. Using near-real-time genome sequencing, we were able to show spread of the Canadian epidemic clone into the United States. The extensive genome data permitted us to identify patterns of geographic dissemination as well as links between emm59 subclonal lineages that cause infections. Mouse and nonhuman primate models of infection demonstrated that the emerged clone is unusually virulent. Transmission of epidemic emm59 strains may have occurred primarily by skin contact, as suggested by an experimental model of skin transmission. In addition, the emm59 strains had a significantly impaired ability to persist in human saliva and to colonize the oropharynx of mice, and seldom caused human pharyngitis. Our study contributes new information to the rapidly emerging field of molecular pathogenomics of bacterial epidemics and illustrates how full-genome data can be used to precisely illuminate the landscape of strain dissemination during a bacterial epidemic. PMID:22330677

Fittipaldi, Nahuel; Beres, Stephen B; Olsen, Randall J; Kapur, Vivek; Shea, Patrick R; Watkins, M Ebru; Cantu, Concepcion C; Laucirica, Daniel R; Jenkins, Leslie; Flores, Anthony R; Lovgren, Marguerite; Ardanuy, Carmen; Lińares, Josefina; Low, Donald E; Tyrrell, Gregory J; Musser, James M

2012-02-11

345

Human Disease Isolates of Serotype M4 and M22 Group A Streptococcus Lack Genes Required for Hyaluronic Acid Capsule Biosynthesis  

PubMed Central

ABSTRACT Group A streptococcus (GAS) causes human pharyngitis and invasive infections and frequently colonizes individuals asymptomatically. Many lines of evidence generated over decades have shown that the hyaluronic acid capsule is a major virulence factor contributing to these infections. While conducting a whole-genome analysis of the in vivo molecular genetic changes that occur in GAS during longitudinal human pharyngeal interaction, we discovered that serotypes M4 and M22 GAS strains lack the hasABC genes necessary for hyaluronic acid capsule biosynthesis. Using targeted PCR, we found that all 491 temporally and geographically diverse disease isolates of these two serotypes studied lack the hasABC genes. Consistent with the lack of capsule synthesis genes, none of the strains produced detectable hyaluronic acid. Despite the lack of a hyaluronic acid capsule, all strains tested multiplied extensively ex vivo in human blood. Thus, counter to the prevailing concept in GAS pathogenesis research, strains of these two serotypes do not require hyaluronic acid to colonize the upper respiratory tract or cause abundant mucosal or invasive human infections. We speculate that serotype M4 and M22 GAS have alternative, compensatory mechanisms that promote virulence.

Flores, Anthony R.; Jewell, Brittany E.; Fittipaldi, Nahuel; Beres, Stephen B.; Musser, James M.

2012-01-01

346

Streptococcus pneumoniae infection: a Canadian perspective.  

PubMed

Streptococcus pneumoniae infections have resulted in significant morbidity and mortality worldwide in children and adults. In Canada, Streptococcus pneumoniae remains one of the leading causes of infectious disease including pneumonia, meningitis, bacteremia and otitis media. Although the widespread use of pneumococcal conjugate vaccines (PCVs) in Canadian children has reduced the incidence of pneumococcal diseases associated with vaccine-serotypes, rapid increase of non-vaccine serotypes in carriage and pneumococcal infections is of great concern to clinicians. The main goal of this review is to provide an overall picture of invasive pneumococcal diseases (IPD) in Canada for the past few decades, including serotype changes and shifts in antibiotic resistance patterns. The effects of PCV vaccines on incidence, serotype distribution, antibiotic resistance of pneumococcal infections and nasopharyngeal (NP) carriage are discussed. We also examined historical outbreaks of Streptococcus pneumoniae and their public health impact. Recent developments in universal protein vaccines against pneumococcus show promise. PMID:23977934

Deng, Xianding; Church, Deirdre; Vanderkooi, Otto G; Low, Donald E; Pillai, Dylan R

2013-08-01

347

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...

348

CSF Proteins as Discreminatory Markers of Tubercular and Pyogenic Meningitis  

PubMed Central

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.

Shekhar, Ravi; Rao, J. Rama; Devi, K. Ambika; Rao, R Babu

2013-01-01

349

CSF Proteins as Discreminatory Markers of Tubercular and Pyogenic Meningitis.  

PubMed

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

Shekhar, Ravi; Rao, J Rama; Devi, K Ambika; Rao, R Babu

2013-08-01

350

Streptococcus sanguinis and the sera of patients with Behçet's disease stimulate membrane expression of ?-enolase in human dermal microvascular endothelial cells.  

PubMed

The glycolytic enzyme ?-enolase is a plasminogen-binding protein that is generally found in the cytosolic compartment. However, ?-enolase can also be expressed on cell surfaces following an inflammatory stimulus via an unknown mechanism. We investigated the effects of Streptococcus sanguinis (S. sanguinis) and the sera of patients with Behçet's disease (BD) on the expression and distribution of ?-enolase in human dermal microvascular endothelial cells (HDMECs). HDMECs were stimulated with cultured S. sanguinis and the sera of active BD patients. HDMECs incubated for 6, 12 or 24 h were harvested, and the membrane and cytoplasmic fractions of proteins were extracted. The expression and distribution of ?-enolase were analyzed using subcellular fractionation and immunoblotting. Subcellular localization of ?-enolase was also assessed by immunocytochemistry. S. sanguinis stimulated the expression of ?-enolase in the membranous compartment of HDMECs in a dose-dependent manner. This pattern was also observed in HDMECs incubated with BD patients' sera. Although incubation of HDMECs with sera from healthy controls increased membrane expression of ?-enolase, incubation with BD sera resulted in earlier and higher expression of this glycoprotein in the cellular membrane of HDMECs. Immunocytochemistry revealed strong immunostaining of ?-enolase in the cytoplasm and cytoplasmic membrane of HDMECs incubated with S. sanguinis or BD patients' sera. In conclusions, these results indicate that S. sanguinis infection and the sera of BD patients with active disease are inflammatory stimuli that can induce membranous ?-enolase expression in endothelial cells. Membrane-expressed ?-enolase could potentially react with anti-?-enolase antibodies in BD patients' sera, resulting in increased inflammation. PMID:23131860

Cho, Suhyun; Zheng, Zhenlong; Cho, Sung Bin; Choi, Min Ju; Lee, Kwang Hoon; Bang, Dongsik

2012-11-07

351

Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens.  

PubMed

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

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

2009-07-22

352

Role of mRNA Stability in Growth Phase Regulation of Gene Expression in the Group A Streptococcus? †  

PubMed Central

The impressive disease spectrum of Streptococcus pyogenes (the group A streptococcus [GAS]) is believed to be determined by its ability to modify gene expression in response to environmental stimuli. Virulence gene expression is controlled tightly by several different transcriptional regulators in this organism. In addition, expression of most, if not all, GAS genes is determined by a global mechanism dependent on growth phase. To begin an analysis of growth-phase regulation, we compared the transcriptome 2 h into stationary phase to that in late exponential phase of a serotype M3 GAS strain. We identified the arc transcript as more abundant in stationary phase in addition to the sag and sda transcripts that had been previously identified. We found that in stationary phase, the stability of sagA, sda, and arcT transcripts increased dramatically. We found that polynucleotide phosphorylase (PNPase [encoded by pnpA]) is rate limiting for decay of sagA and sda transcripts in late exponential phase, since the stability of these mRNAs was greater in a pnpA mutant, while stability of control mRNAs was unaffected by this mutation. Complementation restored the wild-type decay rate. Furthermore, in a pnpA mutant, the sagA mRNA appeared to be full length, as determined by Northern hybridization. It seems likely that mRNAs abundant in stationary phase are insensitive to the normal decay enzyme(s) and instead require PNPase for this process. It is possible that PNPase activity is limited in stationary phase, allowing persistence of these important virulence factor transcripts at this phase of growth.

Barnett, Timothy C.; Bugrysheva, Julia V.; Scott, June R.

2007-01-01

353

Influence of ampicillin, ceftiofur, attenuated live PRRSV vaccine, and reduced dose Streptococcus suis exposure on disease associated with PRRSV and S. suis coinfection.  

PubMed

The objective of this research was to evaluate the efficacy of two antimicrobials (ampicillin and ceftiofur), a modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine, and low dose exposure to Streptococcus suis on disease associated with PRRSV/S. suis coinfection. Fifty-six, crossbred, PRRSV-free pigs were weaned at 10-12 days of age and randomly assigned to five treatment groups. All pigs were inoculated with 2ml of 10(6.4) TCID50/ml of high virulence PRRSV isolate VR-2385 intranasally at 29-31 days of age (day 0 of the study) followed 7 days later by intranasal inoculation with 2ml of 10(8.9)colony forming units(CFU)/ml S. suis type 2 isolate ISU VDL #40634/94. Pigs in group 1 (n=10) served as untreated infected positive controls. Pigs in group 2 (n=12) were treated with 5.0 mg/kg ceftiofur hydrochloride intramuscularly (IM) on days 8, 11, and 14. Pigs in group 3 (n=11) were treated with 11 mg/kg ampicillin IM on days 8-10. Pigs in group 4 (n=12) were vaccinated 14 days prior to PRRSV challenge with a commercial modified-live PRRSV vaccine. Pigs in group 5 (n=11) were exposed to a 1:100 dilution of the S. suis challenge inoculum 19 days prior to S. suis challenge. Mortality was 80, 25, 82, 83, and 36% in groups 1-5, respectively. The reduced dose S. suis exposure had some residual virulence, evidenced by S. suis induced meningitis in two pigs after exposure. Treatment with ceftiofur hydrochloride and reduced dose exposure to S. suis were the only treatments which significantly (P<0.05) reduced mortality associated with PRRSV/S. suis coinfection, significantly (P<0.05) reduced recovery of S. suis from tissues at necropsy, and significantly (P<0.05) reduced the severity of gross lung lesions. PMID:11118739

Schmitt, C S; Halbur, P G; Roth, J A; Kinyon, J M; Kasorndorkbua, C; Thacker, B

2001-01-01

354

Effect of Cratoxylum formosum on innate immune response and disease resistance against Streptococcus agalactiae in tilapia Oreochromis niloticus  

Microsoft Academic Search

The effect of aqueous extract of Cratoxylum formosum on innate immune response and disease resistance in tilapia Oreochromis niloticus was investigated. The fish were fed diets containing 0% (control), 0.5% (diet 1), 1% (diet 2), and 1.5% (diet 3) of C. formosum aqueous extract for 30 days. At the end of the experimental period, parameters of innate immune response including phagocytosis

Pongsak Rattanachaikunsopon; Parichat Phumkhachorn

2010-01-01

355

Molecular insight into invasive group A streptococcal disease  

Microsoft Academic Search

Streptococcus pyogenes is also known as group A Streptococcus (GAS) and is an important human pathogen that causes considerable morbidity and mortality worldwide. The GAS serotype M1T1 clone is the most frequently isolated serotype from life-threatening invasive (at a sterile site) infections, such as streptococcal toxic shock-like syndrome and necrotizing fasciitis. Here, we describe the virulence factors and newly discovered

Jason N. Cole; Timothy C. Barnett; Victor Nizet; Mark J. Walker

2011-01-01

356

Minimally Invasive Approach to Eliminate Pyogenic Granuloma: A Case Report  

PubMed Central

Pyogenic granuloma is one of the inflammatory hyperplasia seen in the oral cavity. The term is a misnomer because it is not related to infection and arises in response to various stimuli such as low-grade local irritation, traumatic injury, or hormonal factors. It is most commonly seen in females in their second decade of life due to vascular effects of hormones. Although excisional surgery is the treatment of choice for it, this paper presents the safest and most minimally invasive procedure for the regression of pyogenic granuloma.

Chandrashekar, B.

2012-01-01

357

Antiphagocytic function of an IgG glycosyl hydrolase from Streptococcus equi subsp. equi and its use as a vaccine component.  

PubMed

EndoSe from Streptococcus equi subsp. equi is an enzyme hydrolyzing glycosyl groups on IgG, analogous to EndoS from Streptococcus pyogenes. We here show that the activity of EndoSe leads to an antiphagocytic function and may thus be a contributory factor to immune evasion of S. equi. Despite the damaging effect that EndoSe has on IgG, antibodies against EndoSe can neutralize its function. Antibodies against EndoSe restored the opsonic activity of specific opsonizing antibodies. Mice infected with either S. equi subsp. equi or subsp. zooepidemicus or S. pyogenes could be protected by vaccination with EndoSe. It is speculated that EndoSe could be a suitable vaccine candidate against streptococcal infections. PMID:22615244

Flock, Margareta; Frykberg, Lars; Sköld, Markus; Guss, Bengt; Flock, Jan-Ingmar

2012-05-21

358

Antiphagocytic Function of an IgG Glycosyl Hydrolase from Streptococcus equi subsp. equi and Its Use as a Vaccine Component  

PubMed Central

EndoSe from Streptococcus equi subsp. equi is an enzyme hydrolyzing glycosyl groups on IgG, analogous to EndoS from Streptococcus pyogenes. We here show that the activity of EndoSe leads to an antiphagocytic function and may thus be a contributory factor to immune evasion of S. equi. Despite the damaging effect that EndoSe has on IgG, antibodies against EndoSe can neutralize its function. Antibodies against EndoSe restored the opsonic activity of specific opsonizing antibodies. Mice infected with either S. equi subsp. equi or subsp. zooepidemicus or S. pyogenes could be protected by vaccination with EndoSe. It is speculated that EndoSe could be a suitable vaccine candidate against streptococcal infections.

Flock, Margareta; Frykberg, Lars; Skold, Markus; Guss, Bengt

2012-01-01

359

The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from Streptococcus pyogenes  

Microsoft Academic Search

BACKGROUND: 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.

Changsoo Chang; Penny Coggill; Alex Bateman; Robert D Finn; Marcin Cymborowski; Zbyszek Otwinowski; Wladek Minor; Lour Volkart; Andrzej Joachimiak

2009-01-01

360

Adjuvant immunotherapy with intrapleural Streptococcus pyogenes (OK-432) in lung cancer patients after resection.  

PubMed

A prospective randomized study to evaluate the effect of adjuvant intrapleural OK-432 immunotherapy after resection of lung tumor was conducted in 93 patients with primary lung cancer. Among them, 46 patients had had intrapleural OK-432 injection, 47 had not. In the meantime, serial measurements of serum immunosuppressive acidic protein, of serum interleukin-2 receptor and of the subpopulation of the peripheral blood cells and lymphocytes were performed in all these patients. Patient characteristics in these two groups (sex, age, histological type, pathological stage, type of operation, and performance status) were compatible. The results showed that adjuvant intrapleural OK-432 injection after resection had no beneficial effect on a patient's survival time. Patients who received intrapleural OK-432, had an increase in blood leukocytes, granulocytes and monocytes and serum immunosuppressive acidic protein level. But the cell numbers of total T cells, suppressor/cytoxic cells, helper/inducer cells and natural killer cells of peripheral blood were decreased in the OK-432 positive group. Over half of the patients had transient 1- or 2-day febrile reactions after intrapleural OK-432 injection. It was concluded that neither clinical observation nor immunological monitoring of peripheral blood could demonstrate a beneficial effect from intrapleural OK-432 immunotherapy after complete resection of the tumor. PMID:7954529

Lee, Y C; Luh, S P; Wu, R M; Lee, C J

1994-10-01

361

Hydrogen Peroxide-Mediated Killing of Caenorhabditis elegans by Streptococcus pyogenes  

Microsoft Academic Search

Caenorhabditis elegans is currently introduced as a new, facile, and cheap model organism to study the pathogenesis of gram-negative bacteria such as Pseudomonas aeruginosa and Salmonella enterica serovar Ty- phimurium. The mechanisms of killing involve either diffusible exotoxins or infection-like processes. Recently, it was shown that also some gram-positive bacteria kill C. elegans, although the precise mechanisms of killing remained

W. T. M. Jansen; M. Bolm; R. Balling; G. S. Chhatwal; R. Schnabel

2002-01-01

362

Population Genetics and Linkage Analysis of Loci within the FCT Region of Streptococcus pyogenes  

Microsoft Academic Search

genotype marker for preferred infection of the throat or skin. These findings provide a basis for the hypothesis that FCT region gene products contribute to tissue-specific infection. In an initial series of steps to address this possibility, the FCT regions of 13 strains underwent comparative sequence analysis, the gene content of the FCT region was characterized for 113 strains via

Zerina Kratovac; Anand Manoharan; Feng Luo; Sergio Lizano; Debra E. Bessen

2007-01-01

363

Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease.  

PubMed Central

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.

Burns, E H; Marciel, A M; Musser, J M

1996-01-01

364

Identification of macrolide-resistant clones of Streptococcus pyogenes in Portugal.  

PubMed

Although the overall level of macrolide resistance (27%) has remained stable in Portugal, a rapid inversion in the dominant phenotypes has been noted, with a sharp decrease in the MLS(B) phenotype paralleled by an increase in the M phenotype. To gain further insight into these changes, 325 macrolide-resistant isolates were characterised using a combination of pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The use of Cfr9I, an isoschizomer of SmaI, to digest M phenotype isolates that were refractory to SmaI digestion allowed direct comparison of MLS(B) and M isolates. The results from PFGE and MLST were highly concordant and identified eight major clones, accounting for 92% of the isolates, each of which was associated exclusively with a single macrolide resistance phenotype. Two major clones were found among MLS(B) isolates, characterised by sequence types (ST) 46 (T12/emm22) and ST52 (T28/emm28), whereas clones characterised by ST39 (T4/emm4) and ST28 (T1/emm1) dominated among M isolates. The clone defined by ST52 corresponded to a bacitracin-resistant clone circulating in Europe, and a novel variant expressing other surface antigens (T12/emm22) was detected. The presence of the four major clones has been reported previously in other European countries, suggesting Europe-wide dissemination of a few macrolide-resistant lineages. PMID:16700698

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

2006-06-01

365

Cathelicidin LL37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans  

Microsoft Academic Search

Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococci (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial loads in the tissue even late after the onset of infection. Antimicrobial peptides are important components of the innate host defense, and cathelicidins have been shown to protect against murine necrotic skin infections caused

Linda Johansson; Pontus Thulin; Parham Sendi; Erika Hertzen; Adam Linder; P. Akesson; Donald E. Low; Birgitta Agerberth; Anna Norrby-Teglund

2008-01-01

366

Brain-abscess caused by Streptococcus bovis  

Microsoft Academic Search

Sir, Streptococcusbovis is found in the faeces of10-16 % of healthy persons and animals (i). This causative agent has long been known to be associated with endocarditis (2). It is a frequent cause of bacteremia and gastrointestinal diseases, principally neoplasias of the colon (1). We report a case of brain abscess associated with endocarditis caused by Streptococcus bovis. A 69

M. Montejo Baranda; K. Aguirrebengoa; M. Testillano; C. Aguirre

1985-01-01

367

Recent advances in understanding the molecular basis of group B Streptococcus virulence  

PubMed Central

Group B Streptococcus commonly colonises healthy adults without symptoms, yet under certain circumstances displays the ability to invade host tissues, evade immune detection and cause serious invasive disease. Consequently, Group B Streptococcus remains a leading cause of neonatal pneumonia, sepsis and meningitis. Here we review recent information on the bacterial factors and mechanisms that direct host–pathogen interactions involved in the pathogenesis of Group B Streptococcus infection. New research on host signalling and inflammatory responses to Group B Streptococcus infection is summarised. An understanding of the complex interplay between Group B Streptococcus and host provides valuable insight into pathogen evolution and highlights molecular targets for therapeutic intervention.

Maisey, Heather C.; Doran, Kelly S.; Nizet, Victor

2009-01-01

368

The pathogenicity of the Streptococcus genus.  

PubMed

Streptococcus infections are still one of the important problems facing contemporary medicine. As the World Health Organization (WHO) warns, Streptococcus pneumoniae is responsible for the highest number of pneumonia cases all over the world. Despite an increasing number of pneumococcal vaccinations, incidences of disease connected to this pathogen's infection stay at the same level, which is related to a constantly increasing number of infections caused by nonvaccinal serotypes. Unfortunately, the pathogenicity of bacteria of the Streptococcus genus is also connected to species considered to be physiological flora in humans or animals and, additionally, new species exhibiting pathogenic potential have been discovered. This paper presents an opinion concerning the epidemiology of streptococci infections based on case studies and other publications devoted to this problem. It also sheds new light based on recent reports on the prevention of protective vaccinations application in the case of streptococci infections. PMID:24141975

Krzy?ciak, W; Pluskwa, K K; Jurczak, A; Ko?cielniak, D

2013-07-03

369

rpoB Gene Sequence-Based Identification of Aerobic Gram-Positive Cocci of the Genera Streptococcus, Enterococcus, Gemella, Abiotrophia, and Granulicatella  

Microsoft Academic Search

We developed a new molecular tool based on rpoB gene (encoding the beta subunit of RNA polymerase) sequencing to identify streptococci. We first sequenced the complete rpoB gene for Streptococcus anginosus, S. equinus, and Abiotrophia defectiva. Sequences were aligned with these of S. pyogenes, S. agalactiae, and S. pneumoniae available in GenBank. Using an in-house analysis program (SVARAP), we identified

Michel Drancourt; Veronique Roux; Pierre-Edouard Fournier; Didier Raoult

370

Comparison of cytokine-inducing activity in a lipoteichoic acid-related molecule isolated from a penicillin-killed group A Streptococcus and from untreated bacteria  

Microsoft Academic Search

We previously generated a monoclonal antibody, TS-2, that neutralizes the interferon (IFN)-?-inducing activity of OK-432, a penicillin-killed streptococcal preparation [J. Immunother. 13 (1993) 232]. Expression of the TS-2-binding antigen was markedly higher in the cell wall of the penicillin-treated Streptococcus pyogenes (OK-432) than in the untreated bacteria (Su-BBM). We here isolated the antigens from OK-432 and Su-BBM, designated OK-PSA and

Masato Okamoto; Tetsuya Oshikawa; Go Ohe; Sachiko Furuichi; Hidetomo Nishikawa; Tomoyuki Tano; Takashi Bando; Hideo Yoshida; Shuzo Matsubara; Takashi Matsuno; Motoo Saito; Mitsunobu Sato

2001-01-01

371

A rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection: Methods and disease course  

Microsoft Academic Search

Objective: To describe the clinical and histopathologic progression of a rat model of otitis media with effusion caused by eustachian tube obstruction (ETO) with and without Streptococcus pneumoniae infection. Methods: In 164 rats, the left, bony eustachian tube was approached via a ventral incision and obstructed with dental material. Then 108 rats were infected via an intrabullar injection with S

Otavio B. Piltcher; J. Douglas Swarts; Karin Magnuson; Cuneyt M. Alper; William J. Doyle; Patricia A. Hebda

2002-01-01

372

Post-partum pyogenic abscess containing Ascaris lumbricoides.  

PubMed

We report an unusual case of multiple pyogenic liver abscesses containing Ascariasis lumbricoides in a 35-year-old post-partum female who had delivered 1 month back. Open drainage of liver abscess along with liver worm was done. Patient did well post-operatively. PMID:23961448

Hamid, Raashid; Wani, Sajad; Ahmad, Nawab; Akhter, Afrozah

2013-01-01

373

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 Central

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.

King, Samantha J.; Heath, Peter J.; Luque, Inmaculada; Tarradas, Carmen; Dowson, Christopher G.; Whatmore, Adrian M.

2001-01-01

374

Mutacin production by Streptococcus mutans may promote transmission of bacteria from mother to child.  

PubMed

The production of bacteriocin-like inhibitory substances, mutacins, by mutans streptococci varies among isolates. To find if the degree of mutacin activity of an isolate was related to its transmission between mother and her child, 19 mothers and their 18-month- to 3-year-old children were sampled for their oral mutans streptococci. In addition, the stability of mutacin activity was studied with isolates from the mothers and with isolates from five unrelated 5-year-old children in 5- to 7-year follow-up studies. A total of 145 oral mutans streptococcal isolates were serotyped by immunodiffusion, ribotyped, and mutacin typed by the stab culture technique. Mutacin was produced by 88% of the strains against more than 1 of the 14 indicator strains, representing mutans streptococci, Streptococcus sanguis, Streptococcus salivarius, Streptococcus oralis, Streptococcus gordonii, and Streptococcus pyogenes. Streptococcus mutans isolates showed more inhibitory activity than did Streptococcus sobrinus isolates. Identical ribotypes had similar mutacin activity profiles within a subject, initially and in the follow-up studies, in all but two cases. The mothers harbored a total of 37 different mutans streptococcal ribotypes. Six children were negative for mutans streptococci. Transmission was probable in 9 of 20 mother-child pairs on the basis of the presence of identical strains, as determined by ribotyping and bacteriocin (mutacin) typing. S. mutans strains shared between a mother and her child showed a broader spectrum of inhibitory activity than did nontransmitted strains. In conclusion, the mutacin activity of clinical isolates is reasonably stable, and this virulence factor seems to be of clinical importance in early colonization by S. mutans. PMID:9596721

Grönroos, L; Saarela, M; Mättö, J; Tanner-Salo, U; Vuorela, A; Alaluusua, S

1998-06-01

375

Mutacin Production by Streptococcus mutans May Promote Transmission of Bacteria from Mother to Child  

PubMed Central

The production of bacteriocin-like inhibitory substances, mutacins, by mutans streptococci varies among isolates. To find if the degree of mutacin activity of an isolate was related to its transmission between mother and her child, 19 mothers and their 18-month- to 3-year-old children were sampled for their oral mutans streptococci. In addition, the stability of mutacin activity was studied with isolates from the mothers and with isolates from five unrelated 5-year-old children in 5- to 7-year follow-up studies. A total of 145 oral mutans streptococcal isolates were serotyped by immunodiffusion, ribotyped, and mutacin typed by the stab culture technique. Mutacin was produced by 88% of the strains against more than 1 of the 14 indicator strains, representing mutans streptococci, Streptococcus sanguis, Streptococcus salivarius, Streptococcus oralis, Streptococcus gordonii, and Streptococcus pyogenes. Streptococcus mutans isolates showed more inhibitory activity than did Streptococcus sobrinus isolates. Identical ribotypes had similar mutacin activity profiles within a subject, initially and in the follow-up studies, in all but two cases. The mothers harbored a total of 37 different mutans streptococcal ribotypes. Six children were negative for mutans streptococci. Transmission was probable in 9 of 20 mother-child pairs on the basis of the presence of identical strains, as determined by ribotyping and bacteriocin (mutacin) typing. S. mutans strains shared between a mother and her child showed a broader spectrum of inhibitory activity than did nontransmitted strains. In conclusion, the mutacin activity of clinical isolates is reasonably stable, and this virulence factor seems to be of clinical importance in early colonization by S. mutans.

Gronroos, L.; Saarela, M.; Matto, J.; Tanner-Salo, U.; Vuorela, A.; Alaluusua, S.

1998-01-01

376

Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle  

PubMed Central

The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696).

Egan, Sharon A.; Ward, Philip N.; Watson, Michael; Field, Terence R.

2012-01-01

377

Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle.  

PubMed

The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696). PMID:22383474

Egan, Sharon A; Ward, Philip N; Watson, Michael; Field, Terence R; Leigh, James A

2012-03-01

378

77 FR 26014 - Prospective Grant of Exclusive License: P4 Peptide From Streptococcus Pneumoniae  

Federal Register 2010, 2011, 2012, 2013

...SERVICES Centers for Disease Control and Prevention Prospective...Office, Centers for Disease Control and Prevention (CDC), Department...that the Centers for Disease Control and Prevention (CDC), Technology...of Streptococcus pneumonia infection in humans'') to...

2012-05-02

379

Characterization ofStreptococcus agalactiaeStrains by Multilocus Enzyme Genotype and Serotype: Identification of Multiple Virulent Clone Families That Cause Invasive Neonatal Disease  

Microsoft Academic Search

The chromosomal genotypes of 277 isolates of 16 serotypes ofStreptococcus agalactiaewere characterized by analysis of electrophoretically demonstrable allele profiles at 12 metabolic enzyme loci. The collection com- prised the type strain and 276 strains recovered from French symptomatic and asymptomatic subjects. Sixty-one distinctive electrophoretic types (ETs), representing multilocus clonal genotypes, were identified. ClusteranalysisoftheETsrevealedtwoprimaryphylogeneticdivisionsseparatedbyageneticdistanceof0.62. Division I contained 67 isolates which could

ROLAND QUENTIN; HELENE HUET; FU-SHENG WANG; PIERRE GESLIN; ALAIN GOUDEAU; ANDROBERT K. SELANDER

1995-01-01

380

Streptococcus adherence and colonization.  

PubMed

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

Nobbs, Angela H; Lamont, Richard J; Jenkinson, Howard F

2009-09-01

381

Streptococcus Adherence and Colonization  

PubMed Central

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.

Nobbs, Angela H.; Lamont, Richard J.; Jenkinson, Howard F.

2009-01-01

382

Genetic Relationships between Clinical Isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: Characterization of \\  

Microsoft Academic Search

The oral streptococcal group (mitis phylogenetic group) currently consists of nine recognized species, although the group has been traditionally difficult to classify, with frequent changes in nomenclature over the years. The pneumococcus (Streptococcus pneumoniae), an important human pathogen, is traditionally distin- guished from the most closely related oral streptococcal species Streptococcus mitis and Streptococcus oralis on the basis of three

ADRIAN M. WHATMORE; ANDROULLA EFSTRATIOU; A. PAUL PICKERILL; KAREN BROUGHTON; GEOFFREY WOODARD; DANIEL STURGEON; ROBERT GEORGE; CHRISTOPHER G. DOWSON

2000-01-01

383

Complete genome sequencing and analysis of a Lancefield group G Streptococcus dysgalactiae subsp. equisimilis strain causing streptococcal toxic shock syndrome (STSS)  

PubMed Central

Background Streptococcus dysgalactiae subsp. equisimilis (SDSE) causes invasive streptococcal infections, including streptococcal toxic shock syndrome (STSS), as does Lancefield group A Streptococcus pyogenes (GAS). We sequenced the entire genome of SDSE strain GGS_124 isolated from a patient with STSS. Results We found that GGS_124 consisted of a circular genome of 2,106,340 bp. Comparative analyses among bacterial genomes indicated that GGS_124 was most closely related to GAS. GGS_124 and GAS, but not other streptococci, shared a number of virulence factor genes, including genes encoding streptolysin O, NADase, and streptokinase A, distantly related to SIC (DRS), suggesting the importance of these factors in the development of invasive disease. GGS_124 contained 3 prophages, with one containing a virulence factor gene for streptodornase. All 3 prophages were significantly similar to GAS prophages that carry virulence factor genes, indicating that these prophages had transferred these genes between pathogens. SDSE was found to contain a gene encoding a superantigen, streptococcal exotoxin type G, but lacked several genes present in GAS that encode virulence factors, such as other superantigens, cysteine protease speB, and hyaluronan synthase operon hasABC. Similar to GGS_124, the SDSE strains contained larger numbers of clustered, regularly interspaced, short palindromic repeats (CRISPR) spacers than did GAS, suggesting that horizontal gene transfer via streptococcal phages between SDSE and GAS is somewhat restricted, although they share phage species. Conclusion Genome wide comparisons of SDSE with GAS indicate that SDSE is closely and quantitatively related to GAS. SDSE, however, lacks several virulence factors of GAS, including superantigens, SPE-B and the hasABC operon. CRISPR spacers may limit the horizontal transfer of phage encoded GAS virulence genes into SDSE. These findings may provide clues for dissecting the pathological roles of the virulence factors in SDSE and GAS that cause STSS.

2011-01-01

384

A novel canine model of acute pyogenic spondylodiscitis  

Microsoft Academic Search

New, appropriate in vivo animal models are needed for the study of the pathogenesis of spinal infections and the development\\u000a of novel anti-infection strategies. The purpose of this study was to develop a canine model of acute pyogenic spondylodiscitis\\u000a which can best mimic the human spinal infection process, characterized by separately inoculating bacterial suspension into\\u000a the lumbar intervertebral spaces of

Wei-Hua Chen; Lei-Sheng Jiang; Li-Yang Dai

2009-01-01

385

Pyogenic hepatic abscess after pancreatic resection for chronic pancreatitis.  

PubMed Central

Seventeen patients underwent surgery for alcohol-induced chronic pancreatitis. Three patients later presented with pyogenic liver abscess. The time interval between surgery and presentation with hepatic abscess varied from 6 weeks to 3.5 years. All patients were diabetic, the presentation was insidious and all made an uneventful recovery, two with percutaneous drainage and one with antibiotics alone. The aetiology of this uncommon complication is discussed.

Ravichandran, D.; Carty, N. J.; Johnson, C. D.

1995-01-01

386

Surgical treatment of pyogenic vertebral osteomyelitis with spinal instrumentation  

Microsoft Academic Search

Pyogenic vertebral osteomyelitis responds well to conservative treatment at early stage, but more complicated and advanced\\u000a conditions, including mechanical spinal instability, epidural abscess formation, neurologic deficits, and refractoriness to\\u000a antibiotic therapy, usually require surgical intervention. The subject of using metallic implants in the setting of infection\\u000a remains controversial, although more and more surgeons acknowledge that instrumentation can help the body

Wei-Hua Chen; Lei-Sheng Jiang; Li-Yang Dai

2007-01-01

387

Surgical treatment of pyogenic vertebral osteomyelitis with spinal instrumentation  

PubMed Central

Pyogenic vertebral osteomyelitis responds well to conservative treatment at early stage, but more complicated and advanced conditions, including mechanical spinal instability, epidural abscess formation, neurologic deficits, and refractoriness to antibiotic therapy, usually require surgical intervention. The subject of using metallic implants in the setting of infection remains controversial, although more and more surgeons acknowledge that instrumentation can help the body to combat the infection rather than to interfere with it. The combination of radical debridement and instrumentation has lots of merits such as, restoration and maintenance of the sagittal alignment of the spine, stabilization of the spinal column and reduction of bed rest period. This issue must be viewed in the context of the overall and detailed health conditions of the subjecting patient. We think the culprit for the recurrence of infection is not the implants itself, but is the compromised general health condition of the patients. In this review, we focus on surgical treatment of pyogenic vertebral osteomyelitis with special attention to the role of spinal instrumentation in the presence of pyogenic infection.

Chen, Wei-Hua; Jiang, Lei-Sheng

2006-01-01

388

Complement resistance mechanisms of streptococci  

Microsoft Academic Search

Group A streptococcus (GAS, Streptococcus pyogenes), group B streptococcus (GBS, Streptococcus agalactiae) and pneumococcus (Streptococcus pneumoniae) are all human pathogens that cause significant morbidity and mortality worldwide. These related species cause different spectra of infections spanning from trivial upper respiratory tract or skin infections to septic and severe diseases. In order to cause deep infections and survive in the human

Hanna Jarva; T. Sakari Jokiranta; Reinhard Würzner; Seppo Meri

2003-01-01

389

Acute Pyogenic Iliopsoas Abscess in Taiwan: Clinical Features, Diagnosis, Treatments and Outcome  

Microsoft Academic Search

Objectives: To study the variations of aetiology in the patients with acute pyogenic iliopsoas abscess and identify the appropriate diagnostic modalities as well as therapeutic alternatives (e.g. extraperitoneal or retrofascial percutaneous catheter drainage, PCD) other than surgery.Methods: We carried out a retrospective review and analysis of 25 patients with acute pyogenic iliopsoas abscess in our institution from August 1988 to

J.-J Huang; M.-K Ruaan; R.-R Lan; M.-C Wang

2000-01-01

390

[Cerebrospinal fluid serotonin concentration in pyogenic and tick-borne encephalomeningitis].  

PubMed

Cerebrospinal fluid (CSF) serotonin was determined in 38 patients with pyogenic meningitis and tick-borne encephalitis (TBE) before and after treatment. Increase of CSF serotonin concentration was observed in acute phase of pyogenic meningits and normalized after treatment. PMID:10463248

Siwak, E B; Pawlak, D; Buczko, W; Kondrusik, M; Hermanowska-Szpakowicz, T

391

Tylosin Resistance in Arcanobacterium pyogenes Is Encoded by an Erm X Determinant  

Microsoft Academic Search

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, prophy- laxis, and therapy, notably tylosin, a macrolide antibiotic used extensively for the

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

2003-01-01

392

Intravascular laser therapy in different forms of lung diseases  

NASA Astrophysics Data System (ADS)

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.

Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.

1993-06-01

393

Zoocin A and Lauricidin in Combination Reduce Streptococcus mutans Growth in a Multispecies Biofilm  

Microsoft Academic Search

Dental caries is the most prevalent human infection. It is a multifactorial disease in which the microbial composition of dental plaque plays a major role in the development of clinical symptoms. The bacteria most often implicated in the development of caries are that group of streptococci referred to as the mutans streptococci, in particular Streptococcus mutans and Streptococcus sobrinus. One

K. Lester; R. S. Simmonds

2012-01-01

394

[Neonatal cellulitis caused by group B Streptococcus].  

PubMed

Dermohypodermitis (cellulitis) in newborn infants and in infants aged up to 3 months is uncommon and often not typical. Because group B Streptococcus is known to induce rapid life-threatening complications, early diagnosis leading to emergency treatment is of utmost importance. We report on the case of a 14-day-old girl, initially admitted for viral bronchiolitis with suspected bacterial pulmonary infection, in the absence of any cutaneous injury. The disease actually was cellulitis of the face, caused by group B Streptococcus. The baby presented with a severe septic clinical condition. Early treatment with antibiotics (intravenous amoxicillin for 10 days) allowed a favorable course, with rapid control of the sepsis and regression of the submandibular tumefaction. PMID:22939649

Breinig, S; Roques-Gineste, M; Marcoux, M-O; Bloom, M-C

2012-08-28

395

An uncommon cause of recurrent pyogenic meningitis: pituitary abscess  

PubMed Central

The authors report a 36-year-old male who presented with headache and hypopituitarism, and MRI revealed a ring enhancing lesion with pituitary stalk thickening. During follow-up, he presented with recurrent pyogenic meningitis with persistence of the lesion, therefore a diagnosis of pituitary abscess was considered. He underwent trans-sphenoidal surgery (TSS) with evacuation of pus and received antibiotic treatment for the same. After this he remarkably improved and had no recurrence of symptoms. He is on levothyroxine, glucocorticoids and testosterone replacement therapy for his respective hormone deficits.

Walia, Rama; Bhansali, Anil; Dutta, Pinaki; Shanmugasundar, G; Mukherjee, Kanchan Kumar; Upreti, Vimal; Das, Ashim

2010-01-01

396

Oral pyogenic granuloma: a review of 137 cases.  

PubMed

We retrospectively reviewed 137 cases of histologically confirmed pyogenic granuloma of the oral cavity from the records of the Department of Oral Surgery, Bharat Heavy Electricals Hospital, Trichy, India between 1996 and 2006. The most commonly affected site was the gingiva (n=114, 83%). Mean age of patients was 31 years (range 6-85, male to female ratio 1:2.6). Simple excision is enough to prevent recurrence, but the aetiology and pathogenesis of the lesion must be known to understand its nature. PMID:19203815

Saravana, G H L

2009-02-08

397

Group a streptococcal diseases and their global burden.  

PubMed

Group A streptococcus (GAS) or Streptococcus pyogenes has been recognised as an important human pathogen since early days of modern microbiology, and it remains among the top ten causes of mortality from an infectious disease. Clinical manifestations attributable to this organism are perhaps the most diverse of any single human pathogen. These encompass invasive GAS infections, with high mortality rates despite effective antimicrobials, toxin-mediated diseases including scarlet fever and streptococcal toxic shock syndrome, the autoimmune sequelae of rheumatic fever and glomerulonephritis with potential for long-term disability, and nuisance manifestations of superficial skin and pharyngeal infection, which continue to consume a sizable proportion of healthcare resources. Although an historical perspective indicates major overall reductions in GAS infection rates in the modern era, chiefly as a result of widespread improvements in socioeconomic circumstances, this pathogen remains as a leading infectious cause of global morbidity and mortality. More than 18 million people globally are estimated to suffer from serious GAS disease. This burden disproportionally affects least affluent populations, and is a major cause of illness and death among children and young adults, including pregnant women, in low-resource settings. We review GAS transmission characteristics and prevention strategies, historical and geographical trends and report on the estimated global burden disease attributable to GAS. The lack of systematic reporting makes accurate estimation of rates difficult. This highlights the need to support improved surveillance and epidemiological research in low-resource settings, in order to enable better assessment of national and global disease burdens, target control strategies appropriately and assess the success of control interventions. PMID:23242849

Ralph, Anna P; Carapetis, Jonathan R

2013-01-01

398

Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo  

Microsoft Academic Search

Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism. Convalescent-phase sera from patients with invasive disease were

Kowthar Y. Salim; Dennis G. Cvitkovitch; Peter Chang; Darrin J. Bast; Martin Handfield; Jeffrey D. Hillman; J. C. S. de Azavedo

2005-01-01