scholarly journals One More Disguise in the Stealth Behavior of Streptococcus pyogenes

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Vincent A. Fischetti ◽  
James B. Dale
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Treated Patient ◽  
Vantage Point ◽  
The Body ◽  
Eukaryotic Cells ◽  
Animal Kingdom ◽  
Human Joints ◽  
Hyaluronic Acid Capsule ◽  
Acid Lining

ABSTRACT The ability to hide in the animal kingdom is essential for survival; the same is true for bacteria . Streptococcus pyogenes is considered one of the more successful stealth bacteria in its production of a hyaluronic acid capsule that is chemically identical to the hyaluronic acid lining human joints. It has also acquired the capacity to enter eukaryotic cells to avoid the onslaught of the host’s immune defenses, as well as drugs. From this intracellular vantage point, it may remain dormant from days to weeks, only to cause disease again at a later time, perhaps causing a relapse in a drug-treated patient. We now learn that it is able to enter macrophages as well, enabling the Streptococcus to use this “Trojan horse” approach to be transported to distant sites in the body.

scholarly journals T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 Streptococcus pyogenes

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Yi-Hsuan Chen ◽  
Shao-Hui Li ◽  
Yao-Cheng Yang ◽  
Shu-Hao Hsu ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Epithelial Cells ◽  
Streptococcus Pyogenes ◽  
Whole Blood ◽  
Human Pathogen ◽  
Human Whole Blood ◽  
Epidemiologic Surveillance ◽  
Group A ◽  
Hyaluronic Acid Capsule

ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses. IMPORTANCE Group A Streptococcus (GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.

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

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Waleed Nasser ◽  
Ivan de la Riva Morales ◽  
James M. Musser
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Molecular Mechanisms ◽  
Great Majority ◽  
Whole Genome Sequence ◽  
Phylogenetic Groups ◽  
Content Type ◽  
Genetic Features ◽  
Clade 1 ◽  
Hyaluronic Acid Capsule

ABSTRACTStrains ofemm89Streptococcus pyogeneshave become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125emm89strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3ngapromoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S. pyogenesNADase) and SLO (streptolysin O). Second, all clade 3 strains lack thehasABClocus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report thatemm89strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3emm89S. pyogenes.IMPORTANCES. pyogenes(group A streptococcus [GAS]) causes pharyngitis (“strep throat”), necrotizing fasciitis, and other human infections. Serious infections caused byemm89S. pyogenesstrains have recently increased in frequency in many countries. Based on whole-genome sequence analysis of 1,125 strains recovered from patients on two continents, we discovered that a newemm89clone, termed clade 3, has two distinct genetic features compared to its predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid capsule virulence factor and (ii) increased production of the secreted cytolytic toxins SPN and SLO.emm89S. pyogenesstrains with the clade 3 phenotype (absence of capsule and high expression of SPN and SLO) are highly virulent in mice. These findings provide new understanding of how new virulent clones emerge and cause severe infections worldwide. This newfound knowledge ofS. pyogenesvirulence can be used to help understand future epidemics and conduct new translational research.

scholarly journals The Emergence of Successful Streptococcus pyogenes Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin Expression

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Claire E. Turner ◽  
Matthew T. G. Holden ◽  
Beth Blane ◽  
Carolyne Horner ◽  
Sharon J. Peacock ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Gene Transfer ◽  
Homologous Recombination ◽  
Streptococcus Pyogenes ◽  
High Expression ◽  
Data Set ◽  
Altered Expression ◽  
Content Type ◽  
Hyaluronic Acid Capsule ◽  
Inactivating Mutations

ABSTRACT Gene transfer and homologous recombination in Streptococcus pyogenes has the potential to trigger the emergence of pandemic lineages, as exemplified by lineages of emm1 and emm89 that emerged in the 1980s and 2000s, respectively. Although near-identical replacement gene transfer events in the nga (NADase) and slo (streptolysin O) loci conferring high expression of these toxins underpinned the success of these lineages, extension to other emm genotype lineages is unreported. The emergent emm89 lineage was characterized by five regions of homologous recombination additional to nga-slo, including complete loss of the hyaluronic acid capsule synthesis locus hasABC, a genetic trait replicated in two other leading emm types and recapitulated by other emm types by inactivating mutations. We hypothesized that other leading genotypes may have undergone similar recombination events. We analyzed a longitudinal data set of genomes from 344 clinical invasive disease isolates representative of locations across England, dating from 2001 to 2011, and an international collection of S. pyogenes genomes representing 54 different genotypes and found frequent evidence of recombination events at the nga-slo locus predicted to confer higher toxin genotype. We identified multiple associations between recombination at this locus and inactivating mutations within hasAB, suggesting convergent evolutionary pathways in successful genotypes. This included common genotypes emm28 and emm87. The combination of no or low capsule and high expression of nga and slo may underpin the success of many emergent S. pyogenes lineages of different genotypes, triggering new pandemics, and could change the way S. pyogenes causes disease. IMPORTANCE Streptococcus pyogenes is a genetically diverse pathogen, with over 200 different genotypes defined by emm typing, but only a minority of these genotypes are responsible for the majority of human infection in high-income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that conferred increased expression. Here, we found that recombination of this locus and promoter has occurred in other diverse genotypes, events that may allow these genotypes to expand in the population. We identified an association between the loss of hyaluronic acid capsule synthesis and high toxin expression, which we propose may be associated with an adaptive advantage. As S. pyogenes pathogenesis depends both on capsule and toxin production, new variants with altered expression may result in abrupt changes in the molecular epidemiology of this pathogen in the human population over time.

scholarly journals The emergence of successfulStreptococcus pyogeneslineages through convergent pathways of capsule loss and recombination directing high toxin expression

2019 ◽  
Author(s):  
Claire E. Turner ◽  
Matthew T. G. Holden ◽  
Beth Blane ◽  
Carolyne Horner ◽  
Sharon J. Peacock ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Gene Transfer ◽  
Homologous Recombination ◽  
Streptococcus Pyogenes ◽  
Human Infection ◽  
High Expression ◽  
Genetic Trait ◽  
Altered Expression ◽  
Hyaluronic Acid Capsule ◽  
Inactivating Mutations

AbstractGene transfer and homologous recombination inStreptococcus pyogeneshas the potential to trigger the emergence of pandemic lineages, as exemplified by lineages ofemm1 andemm89 that emerged in the 1980s and 2000s respectively. Although near-identical replacement gene transfer events in thenga(NADase) andslo(Streptolysin O) locus conferring high expression of these toxins underpinned the success of these lineages, extension to otheremm-genotype lineages is unreported. The emergentemm89 lineage was characterised by five regions of homologous recombination additional tonga/slo, including complete loss of the hyaluronic acid capsule synthesis locushasABC,a genetic trait replicated in two other leadingemmtypes and recapitulated by otheremmtypes by inactivating mutations. We hypothesised that other leading genotypes may have undergone a similar recombination events. We analysed a longitudinal dataset of genomes from 344 clinical invasive disease isolates representative of locations across England, dating from 2001 to 2011, and an international collection ofS. pyogenesgenomes representing 54 different genotypes, and found frequent evidence of recombination events at thenga-slolocus predicted to confer higher toxin expression. We identified multiple associations between recombination at this locus and inactivating mutations withinhasA/B,suggesting convergent evolutionary pathways in successful genotypes. This included common genotypesemm28 andemm87. The combination of no or low capsule, and high expression ofngaandslo,may underpin the success for many emergentS. pyogeneslineages of different genotypes, triggering new pandemics and could change the wayS. pyogenescauses disease.ImportanceStreptococcus pyogenesis a genetically diverse pathogen, with over 200 different genotypes defined byemmtyping, but only a minority of these genotypes are responsible for majority of human infection in high income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that conferred increased expression. Here, we found that recombination of this locus and promoter has occurred in other diverse genotypes, events that may allow these genotypes to expand in the population. We identified an association between the loss of hyaluronic acid capsule synthesis and high toxin expression, which we propose may be associated with an adaptive advantage. AsS. pyogenespathogenesis depends both on capsule and toxin production, new variants with altered expression may result in abrupt changes in the molecular epidemiology of this pathogen in the human population over time.

scholarly journals STUDIES ON BACTERIOPHAGES OF HEMOLYTIC STREPTOCOCCI

1957 ◽  
Vol 106 (3) ◽  
pp. 365-384 ◽  
Author(s):  
Richard M. Krause
Keyword(s):  
Cell Wall ◽  
Hyaluronic Acid ◽  
Cell Walls ◽  
Receptor Site ◽  
Surface Proteins ◽  
Phage Antibody ◽  
Group A ◽  
Phage Receptor ◽  
Hyaluronic Acid Capsule ◽  
Isolated Cell

The host ranges of bacteriophages for group A, types 1, 6, 12, and 25 and group C streptococci have been determined. The findings indicate that the susceptibility to these phages is primarily a group-specific phenomenon, although it is modified by several factors such as the hyaluronic acid capsule, lysogeny, and possibly the presence of surface proteins. Phage antibody studies indicate that while the group A phages are antigenically related, they are distinct from the group C phage. This is in agreement with the observation that group A phages are not specific for their homologous streptococcal types. The purified group C carbohydrate inactivates group C phage but not the group A phages, thus suggesting that the carbohydrate, a component of the cell wall, may serve as the phage receptor site. It has not been possible to inactivate the group A phages with group A carbohydrate. Phage lysis of groups A and C streptococci is accompanied by fragmentation of the cell wall since the C carbohydrate has been identified serologically and chemically in the supernate of centrifuged lysates. The immediate lysis of groups A and C hemolytic streptococci and their isolated cell walls by an accesory heat-labile lytic factor in fresh group C lysates is also described.

scholarly journals KARAKTERISTIK FISIK, KIMIA, DAN ORGANOLEPTIK MIE MOSAF (MODIFIED SATOIMO FLOUR) (Colocasia esculenta)

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Eliantosi ◽  
Darius
Keyword(s):  
Hyaluronic Acid ◽  
Wheat Flour ◽  
Consumer Preferences ◽  
Colocasia Esculenta ◽  
Fiber Content ◽  
The Body ◽  
Tolerance Level ◽  
Physical Chemical ◽  
Taro Flour ◽  
The Many

Satoimo rich in Hyaluronic Acid ( HA ) , a substance produced naturally in the body and produce natural collagen . Taro flour relatively smooth and easy to digest useful for the preparation of pastries , cakes , breads and noodles . Noodle is one of the many products that are favored by all the community . Has conducted research aimed to analyze the characteristics of the physical, chemical and organoleptic noodles mosaf ( Colocasia esculenta ) . The treatment is done in this study is a comparison of wheat flour : flour mosaf with variations 450 g : 50 g ; 400 g : 100 g ; 350 g : 150 g ; 300 g : 200 g ; and 250 g : 250 g . The analysis in this study includes the analysis of the fiber content , elasticity and organoleptic ( color, taste, texture dam ) mosaf wet noodle . The results showed that the higher concentration mosaf flour is added , then the noodles fiber content becomes higher but getting lower elasticity , whereas the level of consumer preferences of the parameters of color, flavor and texture of getting down , the tolerance level of the composition of wheat flour : 400 g flour mosaf : 100 g .Keywords : noodles , satoimo , mosaf 

scholarly journals Corporate skin: Biosocial relations, tropes, and institutions in prosthetics research and development

2019 ◽  
Vol 24 (3) ◽  
pp. 360-380
Author(s):  
César E Giraldo Herrera ◽  
Gisli Palsson
Keyword(s):  
Research And Development ◽  
Lower Limb ◽  
Vantage Point ◽  
The Body ◽  
Institutional Practices ◽  
Non Invasive ◽  
Corporate Leader ◽  
History Of

Modern orthopaedic prosthetics imitate biological organs or their functions, interacting with the body of amputees, and are designed and manufactured corporately. Thus, prosthetics constitute a privileged vantage point to witness the intermingling of society and nature, as well as how biosocial relations and institutions are understood, negotiated, and constituted. We develop methodologies of apprenticeship with a worldwide corporate leader in the development and manufacture of non-invasive orthopaedics, to explore the biosocial relations, the tropes, and the institutions involved in the research and development of lower-limb prosthetics. The ethnography reveals how understandings of biosocial relations are influenced by and simultaneously permeate corporate institutional practices, constituting specific organic tropes, such as the corporate skin. This trope reflects the continuous negotiation of understandings of what the skin is and what it does, of the biosocial relations associated with it, of the history of the company, its products, and how its institutional practices are being shaped by these understandings.

scholarly journals Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements

2014 ◽  
Vol 82 (12) ◽  
pp. 5293-5307 ◽  
Author(s):  
Marina Falaleeva ◽  
Oliwia W. Zurek ◽  
Robert L. Watkins ◽  
Robert W. Reed ◽  
Hadeel Ali ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Streptococcus Pyogenes ◽  
Regulatory Region ◽  
Regulatory System ◽  
Invasive Disease ◽  
Negative Regulator ◽  
Mobility Shift ◽  
Putative Promoter ◽  
Transcriptional Terminator ◽  
Content Type

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

Dermal filler migration complications following lip augmentation procedures

2020 ◽  
Vol 9 (7) ◽  
pp. 276-281
Author(s):  
Danielle Davy
Keyword(s):  
Hyaluronic Acid ◽  
Rare Complication ◽  
Post Treatment ◽  
The Body ◽  
Dermal Filler ◽  
Dermal Fillers ◽  
Short Term ◽  
Lip Augmentation ◽  
Permanent Fillers

Filler migration is a rare complication of dermal filler treatment. Although most research has found that more permanent fillers, such as silicone, are more likely to migrate due to their long-term presence in the body, there have also been reported cases of filler migration from short-term hyaluronic acid-based dermal fillers. As lip augmentation procedures are fast becoming one of the most frequently requested treatments in medical aesthetics, this article looks at the longevity of hyaluronic acid lip dermal fillers, while also aiming to assess the cause of dermal filler post-treatment migration and evaluating how to minimise its risk.

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