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Bram Vanderborght - One of the best experts on this subject based on the ideXlab platform.
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novel lockable and stackable compliant actuation unit for modular Spea actuators
International Conference on Robotics and Automation, 2019Co-Authors: Glenn Mathijssen, Dirk Lefeber, Raphael Furnemont, Elias Saerens, Manolo Garabini, Manuel G Catalano, Antonio Bicchi, Bram VanderborghtAbstract:On compliant robotic systems, modularity is recently adopted for the ease of up- and downscaling and the possibility to downgrade the costs, by moving towards the combination of standard units instead of custom designs. However, modularity on the actuator level itself lacks more thorough evaluation. We have developed a novel lockable and stackable compliant actuation unit which can be used to form modular series-parallel elastic actuators (+Spea). This letter describes the modular +Spea layer architecture and discusses its two-way overrunner and rubber springs in detail, while providing experimental validation on each component as well. First experiments show the layer can deliver up to 20 Nm. Finally, we present how a manipulator can be equipped with the modular +Spea layers.
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Spea introduction drastic actuator energy requirement reduction by symbiosis of parallel motors springs and locking mechanisms
International Conference on Robotics and Automation, 2016Co-Authors: Glenn Mathijssen, Branko Brackx, Dirk Lefeber, Raphael Furnemont, Tom Verstraten, Jasmina Premec, Rene Jimenez, Bram VanderborghtAbstract:Modern actuation schematics become increasingly ingenious by deploying springs and locking mechanisms in series and/or parallel. Many of these solutions are, however, tailored for a specific application and a general schematic that allows for drastic energy reduction remains a challenge. We have developed a series-parallel elastic actuator (Spea) based on a symbiosis of multiple motors, springs and locking mechanisms in parallel, which we call +Spea. This paper introduces the novel +Spea concept. We present a first prototype, a +Spea model and a control strategy that optimizes the energy consumption, and experiments to verify the working principle and recruitment strategy. The experiments show a good fit with the model and currently the actuator reduces the required energy in blocked output experiments by more than a factor 4.
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variable recruitment of parallel elastic elements series parallel elastic actuators Spea with dephased mutilated gears
IEEE-ASME Transactions on Mechatronics, 2015Co-Authors: Glenn Mathijssen, Dirk Lefeber, Bram VanderborghtAbstract:The development and control of variable stiffness actuators (VSAs) led to the capability of embodying physical principles of safety and energy-efficiency compared to traditional stiff servomotors. However, the output torque range and efficiency of servomotors and VSAs are still insufficient which hinders the development of machines with performances comparable to a human. We have developed a novel compliant actuation concept, series-parallel elastic actuation (Spea), that addresses these problems. The novelty being the variable recruitment of parallel elastic elements and adaptive load cancellation. In this paper, we propose the use of multiple dephased mutilated gears with locking ring and plate, as intermittent mechanisms, linked in parallel to the motor. As a result, the motor torque requirements can be lowered, as such the motor can be downscaled and the efficiency can be drastically increased. After an abstract description of the Spea concept and an outline of the biological basis, we present the first unidirectional Spea proof of concept (PoC) setup. Experiments on this PoC setup endorse the feasibility of the Spea concept. The results match the modeled trend of a lowered motor torque and increased energy efficiency.
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design of a novel intermittent self closing mechanism for a maccepa based series parallel elastic actuator Spea
Intelligent Robots and Systems, 2014Co-Authors: Glenn Mathijssen, Branko Brackx, Dirk Lefeber, Raphael Furnemont, Ronald Van Ham, Bram VanderborghtAbstract:High-performance actuators are required for numerous novel applications such as human-robot assistive devices. The torque-to-weight ratio and energy efficiency of current actuation technology is often too low, which limits the performance of novel robots. Therefore, we developed a Series-Parallel Elastic Actuator (Spea) which enables variable recruitment of parallel springs and variable load cancellation. Finding suitable intermittent mechanisms for the Spea is however still challenging. This paper reports on the innovative design of an intermittent self-closing mechanism for a MACCEPA-based Spea that can deliver bi-directional output torque and variable stiffness, while minimizing friction levels. Experiments on a one-layer intermittent self-closing mechanism are conducted to validate the working principle and the proposed model. A demonstrator of the MACCEPA-based Spea with intermittent self-closing mechanism is presented and the experiments validate the modeled output torque and lowered motor torque for different stiffness settings.
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series parallel elastic actuation Spea with intermittent mechanism for reduced motor torque and increased efficiency
Intelligent Robots and Systems, 2013Co-Authors: Glenn Mathijssen, Branko Brackx, Michael Van Damme, Dirk Lefeber, Bram VanderborghtAbstract:Future robots will need to perform complex and versatile tasks comparable to those of humans. Due to the unavailability of suitable actuators, however, novel intelligent and agile robots are often restricted in their performances and development. The limited output torque range and low energy efficiency of current robotic actuators are the main bottlenecks. We have developed a Spea with intermittent mechanism that addresses these problems. The Spea is a novel compliant actuator concept that enables variable recruitment of parallel elastic elements and adaptive load cancellation. This paper describes how a Spea lowers the motor torque and increases the energy efficiency. Experiments on the first proof of concept set-up endorse the practicability of the Spea concept and the modeled trend of a lowered motor torque and increased energy efficiency. We expect that features of the biologically inspired Spea with intermittent mechanism will prove exceedingly useful for robotics applications in the future.
Malak Kotb - One of the best experts on this subject based on the ideXlab platform.
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invasive m1t1 group a streptococcus undergoes a phase shift in vivo to prevent proteolytic degradation of multiple virulence factors by speb
Molecular Microbiology, 2003Co-Authors: Ramy K Aziz, Malak Kotb, Donald E Low, Rita Kansal, Michael J Pabst, Arthur Jeng, Victor NizetAbstract:A globally disseminated strain of M1T1 group A Streptococcus (GAS) has been associated with severe infections in humans including necrotizing fasciitis and toxic shock syndrome. Recent clinicoepidemiologic data showed a striking inverse relationship between disease severity and the degree to which M1T1 GAS express the streptococcal cysteine protease, SpeB. Electrophoretic 2-D gel analysis of the secreted M1T1 proteome, coupled with MALDI-TOF mass spectroscopy, revealed that expression of active SpeB caused the degradation of the vast majority of secreted GAS proteins, including several known virulence factors. Injection of a SpeB+/Spea- M1T1 GAS strain into a murine subcutanous chamber model of infection selected for a stable phase-shift to a SpeB-/Spea+ phenotype that expressed a full repertoire of secreted proteins and possessed enhanced lymphocyte-stimulating capacity. The proteome of the SpeB-in vivo phase-shift form closely matched the proteome of an isogenic speB gene deletion mutant of the original M1T1 isolate. The absence or the inactivation of SpeB allowed proteomic identification of proteins in this M1T1 clone that are not present in the previously sequenced M1 genome including Spea and another bacteriophage-encoded novel streptodornase allele. Further proteomic analysis of the M1T1 SpeB+ and SpeB- phase-shift forms in the presence of a cysteine protease inhibitor demonstrated differences in the expression of several proteins, including the in vivo upregulation of Spea, which occurred independently of SpeB inactivation.
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genetic relatedness and superantigen expression in group a streptococcus serotype m1 isolates from patients with severe and nonsevere invasive diseases
Infection and Immunity, 2000Co-Authors: Sonia Chatellier, Anna Norrbyteglund, Hesham E Basma, Allison Mcgeer, Donald E Low, Rita Kansal, Nahla Ihendyane, Farukh Khambaty, Malak KotbAbstract:The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods. All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 14) invasive GAS infection cases. All the M1 strains studied had the emm1.0 allele and the same streptococcal pyrogenic exotoxin (Spe) genotype, Spea(+) speB(+) speC speF(+) speG(+) speH smeZ(+) ssa. All isolates had the same Spea allotype, Spea2. The randomly amplified polymorphic DNA banding pattern with two different primers was identical for all strains, and pulsed field gel electrophoresis analysis showed that 33 and 30 isolates had identical banding patterns after DNA digestion with SfiI or SmaI, respectively; the nonidentical isolates differed from the main pattern by only one band. A relatively high degree of polymorphism in specific regions of the sic gene was observed among isolates; however, this polymorphism was not associated with disease severity. Likewise, although the phenotypic expression of Spea, SpeB, and SpeF proteins varied among the M1T1 isolates, there was no correlation between the amount of Spe expressed and disease severity. Importantly, mitogenic and cytokine responses induced by partially purified bacterial culture supernatants containing a mixture of expressed superantigens were very similar for isolates from severe and nonsevere cases (P > 0.1). Together, the data indicate that highly related invasive M1T1 isolates, some indistinguishable, can cause disease of varying severity in different individuals. These findings underscore the contribution of host factors to the outcome of invasive GAS infections.
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varying titers of neutralizing antibodies to streptococcal superantigens in different preparations of normal polyspecific immunoglobulin g implications for therapeutic efficacy
Clinical Infectious Diseases, 1998Co-Authors: Anna Norrbyteglund, Hesham E Basma, Jan Andersson, Allison Mcgeer, Donald E Low, Malak KotbAbstract:Inasmuch as normal intravenous polyspecific immunoglobulin G (IVIG) neutralizes the activity of a wide spectrum of superantigens, it may be an efficient adjunctive therapy for diseases associated with superantigen-producing organisms, including severe group A streptococcal diseases. The neutralizing activity against purified superantigens, streptococcal pyrogenic exotoxins (Spe), and a mixture of superantigens present in culture supernatant of clinical group A streptococcal isolates was determined for five IVIG preparations. A significant variation among different IVIG preparations (Po .05) and different lots of the same IVIG brand (Po .044) was found. Neutralization of Spea activity was significantly lower than that of other streptococcal superantigens (P o .05); however, there was no correlation between Spea binding and Spea neutralizing activity in different IVIGs. Plasma samples obtained from patients after IVIG infusion varied in their titers of neutralizing antibodies to culture supernatants prepared from their respective isolates, and this variation paralleled differences in the neutralizing titer of the IVIG lot administered to each patient studied. The study suggests that complete neutralizing activity may be achieved by optimizing the type and/or dose of IVIG used in treatment. Streptococcal toxic shock syndrome and necrotizing fasciitis scores the need for a therapeutic agent that has a broad specificity against a wide variety of group A streptococcal superantiare the two most severe manifestations caused by invasive group A streptococcus, and despite appropriate antibiotic ther- gens.
Shiranee Sriskandan - One of the best experts on this subject based on the ideXlab platform.
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Streptococcal superantigen-induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release.
Clinical and Experimental Immunology, 2019Co-Authors: Frances Davies, Carl Olme, Nicola N. Lynskey, Claire E. Turner, Shiranee SriskandanAbstract:: Streptococcal pyrogenic exotoxin (Spe) A expression is epidemiologically linked to streptococcal tonsillo-pharyngitis and outbreaks of scarlet fever, although the mechanisms by which superantigens confer advantage to Streptococcus pyogenes are unclear. S. pyogenes is an exclusively human pathogen. As the leucocyte profile of tonsil is unique, the impact of Spea production on human tonsil cell function was investigated. Human tonsil cells from routine tonsillectomy were co-incubated with purified streptococcal superantigens or culture supernatants from isogenic streptococcal isolates, differing only in superantigen production. Tonsil cell proliferation was quantified by tritiated thymidine incorporation, and cell surface characteristics assessed by flow cytometry. Soluble mediators including immunoglobulin were measured using enzyme-linked immunosorbent assay. Tonsil T cells proliferated in response to Spea and demonstrated typical release of proinflammatory cytokines. When cultured in the absence of superantigen, tonsil preparations released large quantities of immunoglobulin over 7 days. In contrast, marked B cell apoptosis and abrogation of total immunoglobulin (Ig)A, IgM, and IgG production occurred in the presence of Spea and other superantigens. In Spea-stimulated cultures, T follicular helper (Tfh) cells showed a reduction in C-X-C chemokine receptor (CXCR)5 (CD185) expression, but up-regulation of OX40 (CD134) and inducible T cell co-stimulator (ICOS) (CD278) expression. The phenotypical change in the Tfh population was associated with impaired chemotactic response to CXCL13. Spea and other superantigens cause dysregulated tonsil immune function, driving T cells from Tfh to a proliferating phenotype, with resultant loss of B cells and immunoglobulin production, providing superantigen-producing bacteria with a probable survival advantage.
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complementation of a Spea negative streptococcus pyogenes with Spea effects on virulence and production of streptococcal pyrogenic exotoxin a
Microbial Pathogenesis, 2001Co-Authors: Meera Unnikrishnan, Jonathan Cohen, Shiranee SriskandanAbstract:We have shown previously that an isogenic Spea-negative Streptococcus pyogenes strain did not attenuate virulence in a murine model of necrotizing fasciitis. The aim of this study was to confirm that streptococcal pyrogenic exotoxin A (Spea) is not crucial for streptococcal invasiveness in murine invasive infection. The Spea-negative S. pyogenes (H326) was complemented with Spea extra-chromosomally to create strain H361 which produced 2.2-fold more Spea compared with the parental Spea+wild-type (H305). The growth phase-regulated expression of Speain vitro was unaffected in this strain. Complementation with Spea resulted in reduced virulence and bacterial counts in invasive murine infection. Spea production was quantitated from muscle tissue of infected mice. However, H361 did not produce more Spea than H305 in vivo. We conclude that Spea does not play a key role in invasive murine streptococcal infection.
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molecular analysis of the role of streptococcal pyrogenic exotoxin a Spea in invasive soft tissue infection resulting from streptococcus pyogenes
Molecular Microbiology, 1999Co-Authors: Shiranee Sriskandan, Meera Unnikrishnan, Thomas Krausz, Jonathan CohenAbstract:Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (Spea), in the pathogenesis of necrotizing soft-tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. Spea can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild-type Spea gene in an M1 streptococcal isolate. Supernatants from toxin-negative mutant bacteria demonstrated a 50% reduction in pro-mitogenic activity in HLA DQ-positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild-type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of Spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain-induced mortality was seen after intravenous infection. Intramuscular infection with the Spea-negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified Spea led to a dose-dependent increase in peritoneal neutrophils 6 h after administration. Spea is not a critical virulence factor in invasive soft-tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.
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comparative effects of clindamycin and ampicillin on superantigenic activity of streptococcus pyogenes
Journal of Antimicrobial Chemotherapy, 1997Co-Authors: Shiranee Sriskandan, A Mckee, L Hall, J CohenAbstract:We have tested the ability of Streptococcus pyogenes to produce streptococcal pyrogenic exotoxin A (Spea) and superantigenic activity in the presence of sub-inhibitory concentrations of ampicillin and clindamycin. After 6 h of culture, Spea production by S. pyogenes was higher in broths containing ampicillin (715.7 +/- 296.4 pg/10(6) cfu) than in broths containing clindamycin (167.1 +/- 31.9 pg/10(6) cfu), a difference that was not significant (P = 0.25). Promitogenic activity of bacterial supernatants was also greater in ampicillin-treated cultures (467.5 +/- 17.2 ccpm/10(6) cfu) than in clindamycin-treated cultures (169.2 +/- 8.9 ccpm/10(6) cfu), a difference that was highly significant (P = 0.0001). The data support the use of clindamycin in the treatment of streptococcal toxic shock-like syndrome, in order to inhibit superantigen synthesis.
Karin S Pfennig - One of the best experts on this subject based on the ideXlab platform.
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female toads engaging in adaptive hybridization prefer high quality heterospecifics as mates
Science, 2020Co-Authors: Catherine Chen, Karin S PfennigAbstract:Hybridization-interbreeding between species-is generally thought to occur randomly between members of two species. Contrary to expectation, female plains spadefoot toads (Spea bombifrons) can increase their evolutionary fitness by preferentially mating with high-quality males of another species, the Mexican spadefoot toad (Spea multiplicata). Aspects of Mexican spadefoot males' mating calls predict their hybrid offspring's fitness, and plains spadefoot females prefer Mexican spadefoot males on the basis of these attributes, but only in populations and ecological conditions where hybridization is adaptive. By selecting fitness-enhancing mates of another species, females increase hybridization's benefits and exert sexual selection across species. Nonrandom mating between species can thereby increase the potential for adaptive gene flow between species so that adaptive introgression is not simply happenstance.
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asymmetric reproductive character displacement in male aggregation behaviour
Proceedings of The Royal Society B: Biological Sciences, 2011Co-Authors: Karin S Pfennig, Alyssa StewartAbstract:Reproductive character displacement—the evolution of traits that minimize reproductive interactions between species—can promote striking divergence in male signals or female mate preferences between populations that do and do not occur with heterospecifics. However, reproductive character displacement can affect other aspects of mating behaviour. Indeed, avoidance of heterospecific interactions might contribute to spatial (or temporal) aggregation of conspecifics. We examined this possibility in two species of hybridizing spadefoot toad (genus Spea). We found that in Spea bombifrons sympatric males were more likely than allopatric males to associate with calling males. Moreover, contrary to allopatric males, sympatric S. bombifrons males preferentially associated with conspecific male calls. By contrast, Spea multiplicata showed no differences between sympatry and allopatry in likelihood to associate with calling males. Further, sympatric and allopatric males did not differ in preference for conspecifics. However, allopatric S. multiplicata were more variable than sympatric males in their responses. Thus, in S. multiplicata, character displacement may have refined pre-existing aggregation behaviour. Our results suggest that heterospecific interactions can foster aggregative behaviour that might ultimately contribute to clustering of conspecifics. Such clustering can generate spatial or temporal segregation of reproductive activities among species and ultimately promote reproductive isolation.
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development and characterization of nine polymorphic microsatellite markers for mexican spadefoot toads Spea multiplicata with cross amplification in plains spadefoot toads s bombifrons
Molecular Ecology Resources, 2008Co-Authors: Amber M Rice, D E Pearse, T Becker, R A Newman, C Lebonville, George R Harper, Karin S PfennigAbstract:We developed nine polymorphic microsatellite markers for the Mexican spadefoot toad, Spea multiplicata. Allele numbers range from five to 12, with observed heterozygosities from 0.48 to 0.87. Because two loci are in linkage disequilibrium, these nine loci provide eight independent markers. Three loci exhibit departure from Hardy-Weinberg equilibrium, possibly resulting from null alleles or population admixture. These markers will be useful for assessing population structure and relatedness in S. multiplicata. Based on our success at cross-amplification in the Plains spadefoot toad (Spea bombifrons), these loci also may be useful in this species with additional optimization.
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female spadefoot toads compromise on mate quality to ensure conspecific matings
Behavioral Ecology, 2000Co-Authors: Karin S PfennigAbstract:When high-quality conspecifics resemble heterospecifics, females may be unable to engage effectively in both species recognition (identification of conspecifics) and mate-quality recognition (identification of high-quality mates). Consequently, females that engage primarily in mate-quality recognition may risk heterospecific matings, and females that engage primarily in species recognition may risk mating with low-quality mates. I examined the evolutionary consequences of this conflict between species and mate-quality recognition in spadefoot toads, Spea multiplicata. I compared mate preferences and the fitness consequences of these preferences in spadefoot toad populations that did and did not overlap with congeners. In non-overlapping populations, S. multiplicata females preferred an extreme call character resembling that of heterospecifics, and they had more eggs fertilized. In overlapping populations, S. multiplicata females preferred those call characteristics that were closest to the norm for their population, and they did not receive the benefit of enhanced fertilization success. Thus, S. multiplicata females appear to trade off species and mate-quality recognition, such that those co-occurring with heterospecifics forgo the benefits of high-quality matings to ensure conspecific matings. These results suggest that the interaction between species and mate-quality recognition may influence mate choice decisions in important and nonintuitive ways. Key words: mate choice, mate-quality recognition, species recognition, Scaphiopus couchii, Spea bombifrons, Spea multiplicata. [Behav Ecol 11:220–227 (2000)]
Rita Kansal - One of the best experts on this subject based on the ideXlab platform.
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invasive m1t1 group a streptococcus undergoes a phase shift in vivo to prevent proteolytic degradation of multiple virulence factors by speb
Molecular Microbiology, 2003Co-Authors: Ramy K Aziz, Malak Kotb, Donald E Low, Rita Kansal, Michael J Pabst, Arthur Jeng, Victor NizetAbstract:A globally disseminated strain of M1T1 group A Streptococcus (GAS) has been associated with severe infections in humans including necrotizing fasciitis and toxic shock syndrome. Recent clinicoepidemiologic data showed a striking inverse relationship between disease severity and the degree to which M1T1 GAS express the streptococcal cysteine protease, SpeB. Electrophoretic 2-D gel analysis of the secreted M1T1 proteome, coupled with MALDI-TOF mass spectroscopy, revealed that expression of active SpeB caused the degradation of the vast majority of secreted GAS proteins, including several known virulence factors. Injection of a SpeB+/Spea- M1T1 GAS strain into a murine subcutanous chamber model of infection selected for a stable phase-shift to a SpeB-/Spea+ phenotype that expressed a full repertoire of secreted proteins and possessed enhanced lymphocyte-stimulating capacity. The proteome of the SpeB-in vivo phase-shift form closely matched the proteome of an isogenic speB gene deletion mutant of the original M1T1 isolate. The absence or the inactivation of SpeB allowed proteomic identification of proteins in this M1T1 clone that are not present in the previously sequenced M1 genome including Spea and another bacteriophage-encoded novel streptodornase allele. Further proteomic analysis of the M1T1 SpeB+ and SpeB- phase-shift forms in the presence of a cysteine protease inhibitor demonstrated differences in the expression of several proteins, including the in vivo upregulation of Spea, which occurred independently of SpeB inactivation.
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reciprocal temporal expression of Spea and speb by invasive m1t1 group a streptococcal isolates in vivo
Infection and Immunity, 2001Co-Authors: Shahana U Kazmi, Anna Norrbyteglund, Donald E Low, Rita Kansal, Ramy K Aziz, Massoumeh Hooshdaran, Abdelbaset HalimAbstract:The streptococcal pyrogenic exotoxins (Spes) play a central role in the pathogenesis of invasive group A streptococcal (GAS) infections. The majority of recent invasive GAS infections have been caused by an M1T1 strain that harbors the genes for several streptococcal superantigens, including Spea, speB, speF, speG, and smeZ. However, considerable variation in the expression of Spe proteins among clonal M1 isolates has been found, and many of the Spea-positive M1 strains do not produce detectable amounts of Spea in vitro. This study was designed to test the hypothesis that Spea gene expression can be induced in vivo. A mouse infection chamber model that allows sequential sampling of GAS isolates at various time points postinfection was developed and used to monitor the kinetics of Spe production in vivo. Micropore Teflon diffusion chambers were implanted subcutaneously in BALB/c mice, and after 3 weeks the pores became sealed with connective tissue and sterile fluid containing a white blood cell infiltrate accumulated inside the infection chambers. Representative clonal M1T1 isolates expressing no detectable Spea were inoculated into the implanted chambers, and the expression of Spea in the aspirated aliquots of the chamber fluid was analyzed on successive days postinfection. Expression of Spea was detected in the chamber fluid as early as days 3 to 5 postinfection in most animals, with a significant increase in expression by day 7 in all infected mice. Isolates recovered from the chamber and grown in vitro continued to produce Spea even after 21 passages in vitro, suggesting stable switch on of the Spea gene. A temporal relation between the upregulation of Spea expression and the downregulation of SpeB expression was observed in vivo. These data suggest that in vivo host and/or environmental signals induced Spea gene expression and suppressed speB gene expression. This underscores the role of the host-pathogen interaction in regulating the expression of streptococcal virulence factors in vivo. The model described here should facilitate such studies.
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genetic relatedness and superantigen expression in group a streptococcus serotype m1 isolates from patients with severe and nonsevere invasive diseases
Infection and Immunity, 2000Co-Authors: Sonia Chatellier, Anna Norrbyteglund, Hesham E Basma, Allison Mcgeer, Donald E Low, Rita Kansal, Nahla Ihendyane, Farukh Khambaty, Malak KotbAbstract:The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods. All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 14) invasive GAS infection cases. All the M1 strains studied had the emm1.0 allele and the same streptococcal pyrogenic exotoxin (Spe) genotype, Spea(+) speB(+) speC speF(+) speG(+) speH smeZ(+) ssa. All isolates had the same Spea allotype, Spea2. The randomly amplified polymorphic DNA banding pattern with two different primers was identical for all strains, and pulsed field gel electrophoresis analysis showed that 33 and 30 isolates had identical banding patterns after DNA digestion with SfiI or SmaI, respectively; the nonidentical isolates differed from the main pattern by only one band. A relatively high degree of polymorphism in specific regions of the sic gene was observed among isolates; however, this polymorphism was not associated with disease severity. Likewise, although the phenotypic expression of Spea, SpeB, and SpeF proteins varied among the M1T1 isolates, there was no correlation between the amount of Spe expressed and disease severity. Importantly, mitogenic and cytokine responses induced by partially purified bacterial culture supernatants containing a mixture of expressed superantigens were very similar for isolates from severe and nonsevere cases (P > 0.1). Together, the data indicate that highly related invasive M1T1 isolates, some indistinguishable, can cause disease of varying severity in different individuals. These findings underscore the contribution of host factors to the outcome of invasive GAS infections.
