Humanized Plasminogen Mouse Model to Study Group A Streptococcus Invasive Disease

2020 ◽  
pp. 309-316
Author(s):  
Tania Rivera-Hernandez ◽  
Mark J. Walker
Keyword(s):  
Mouse Model ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Study Group ◽  
Group A

scholarly journals Regulatory Role of GSK-3βon NF-κB, Nitric Oxide, and TNF-αin Group A Streptococcal Infection

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Tzu Chang ◽  
Chia-Ling Chen ◽  
Chiou-Feng Lin ◽  
Shiou-Ling Lu ◽  
Miao-Huei Cheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Model ◽  
Group A Streptococcus ◽  
Glycogen Synthase ◽  
Critical Issue ◽  
No Production ◽  
Group A ◽  
Oxide Synthase

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β(GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3βin GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3βoccurred after GAS infection, and inhibition of GSK-3βreduced iNOS expression and NO production. Furthermore, GSK-3βinhibitors reduced NF-κB activation and subsequent TNF-αproduction, which indicates that GSK-3βacts upstream of NF-κB in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3βinhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-αand improved the survival rate. The inhibition of GSK-3βto moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

scholarly journals Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

2014 ◽  
Vol 63 (12) ◽  
pp. 1670-1678 ◽  
Author(s):  
John D. Steemson ◽  
Nicole J. Moreland ◽  
Deborah Williamson ◽  
Julie Morgan ◽  
Philip E. Carter ◽  
...  
Keyword(s):  
New Zealand ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
T Antigen ◽  
Clinical Group ◽  
Wide Range ◽  
Life Threatening ◽  
Group A ◽  
The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

FbaA- and M protein-based multi-epitope vaccine elicits strong protective immune responses against group A streptococcus in mouse model

2014 ◽  
Vol 16 (5) ◽  
pp. 409-418 ◽  
Author(s):  
Cuiqing Ma ◽  
Zheng Liu ◽  
Wenjian Li ◽  
Xuesong Qian ◽  
Song Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Group A Streptococcus ◽  
M Protein ◽  
Epitope Vaccine ◽  
Group A

scholarly journals Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo

2005 ◽  
Vol 73 (9) ◽  
pp. 6026-6038 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Dennis G. Cvitkovitch ◽  
Peter Chang ◽  
Darrin J. Bast ◽  
Martin Handfield ◽  
...  
Keyword(s):  
Murine Model ◽  
Vibrio Vulnificus ◽  
Group A Streptococcus ◽  
Hypothetical Protein ◽  
Invasive Disease ◽  
Antigenic Determinants ◽  
Expression Library ◽  
Group A

ABSTRACT 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 pooled, adsorbed against antigens derived from in vitro-grown GAS, and used to screen a GAS genomic expression library. A murine model of invasive GAS disease was included as an additional source of sera for screening. Sequencing DNA inserts from clones reactive with both human and mouse sera indicated 16 open reading frames with homology to genes involved in metabolic activity to genes of unknown function. Of these, seven genes were assessed for their differential expression by quantitative real-time PCR both in vivo, utilizing a murine model of invasive GAS disease, and in vitro at different time points of growth. Three gene products—a putative penicillin-binding protein 1A, a putative lipoprotein, and a conserved hypothetical protein homologous to a putative translation initiation inhibitor in Vibrio vulnificus—were upregulated in vivo, suggesting that these genes play a role during invasive disease.

Full-Genome Dissection of an Epidemic of Severe Invasive Disease Caused by a Hypervirulent, Recently Emerged Clone of Group A Streptococcus

2012 ◽  
Vol 180 (4) ◽  
pp. 1522-1534 ◽  
Author(s):  
Nahuel Fittipaldi ◽  
Stephen B. Beres ◽  
Randall J. Olsen ◽  
Vivek Kapur ◽  
Patrick R. Shea ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Invasive Disease ◽  
Full Genome ◽  
Group A

scholarly journals Genetic Relatedness and Superantigen Expression in Group A Streptococcus Serotype M1 Isolates from Patients with Severe and Nonsevere Invasive Diseases

2000 ◽  
Vol 68 (6) ◽  
pp. 3523-3534 ◽  
Author(s):  
Sonia Chatellier ◽  
Nahla Ihendyane ◽  
Rita G. Kansal ◽  
Farukh Khambaty ◽  
Hesham Basma ◽  
...  
Keyword(s):  
Disease Severity ◽  
Genetic Relatedness ◽  
Group A Streptococcus ◽  
Phenotypic Expression ◽  
Invasive Disease ◽  
Banding Patterns ◽  
Clinical Criteria ◽  
Group A ◽  
High Degree ◽  
Culture Supernatants

ABSTRACT 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.

scholarly journals A locus of group A streptococcus involved in invasive disease and DNA transfer

2002 ◽  
Vol 46 (1) ◽  
pp. 87-99 ◽  
Author(s):  
Carlos Hidalgo-Grass ◽  
Miriam Ravins ◽  
Mary Dan-Goor ◽  
Joseph Jaffe ◽  
Allon E. Moses ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Invasive Disease ◽  
Dna Transfer ◽  
Group A

scholarly journals 1200. Risk of group A streptococcal Transmission Among the Pediatric Population in the Houston Area

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S621-S622
Author(s):  
zain I Alamarat ◽  
Lauren Sommer ◽  
Jonathon C McNeil ◽  
Anthony R Flores
Keyword(s):  
Group A Streptococcus ◽  
Medical Center ◽  
Pediatric Population ◽  
National Level ◽  
Invasive Disease ◽  
Streptococcal Toxic Shock Syndrome ◽  
Passive Surveillance System ◽  
Superficial Skin ◽  
Group A ◽  
Index Cases

Abstract Background Disease due to group A Streptococcus (GAS) occurs frequently in children and usually manifests as pharyngitis or superficial skin infections. However, invasive disease (iGAS) such as necrotizing fasciitis or streptococcal toxic shock syndrome is responsible for significant morbidity and mortality. National-level surveillance at the Centers for Disease Control and Prevention (CDC) estimates >10,000 cases and ~1,500 deaths due to iGAS occur annually in the US. Much interest revolves around the ability to detect potential transmission events (PTEs) of GAS disease using surveillance data as such information may change recommendations for chemoprophylaxis of close contacts. Studies by the CDC have shown a secondary attack rate from 66.1 to 102 /100,000, primarily occurring among older adults with co-morbidities. However, previous studies were limited in that the GAS surveillance was limited to iGAS disease. Methods Retrospective study using a comprehensive GAS passive surveillance system. GAS isolates and associated metadata were obtained from 2 hospital systems in the Texas Medical Center from 2017-2019. Molecular emm typing of GAS isolates was performed using the CDC protocol. PTEs were defined based on GAS disease isolates originating from the same zip code, occurring within 30 days of each other, and of the same emm type. Results A total of 1291 isolates were included in the study – 94 PTEs were identified representing 168 individual GAS isolates of which 74 were defined as index cases. The 4 most common GAS emm types identified among PTEs were emm1 (43/94, 45.7%), emm12 (30/94, 31.9%), emm4 (6/94, 6.4%), and emm6 (5/94, 5.3%). Index cases most frequently resulted in a single PTE (n=74) with an average number of PTEs per index case of 1.3 (range 1 to 3 PTEs). From index cases, 10 GAS isolates were derived from invasive disease (10/74, 13.5%) and 6 from skin and soft tissue infections (SSTI; 6/74, 8.1%). A substantial proportion of PTEs resulted in iGAS (9/94, 9.5%) and SSTI (10/94, 10.6%). Conclusion Using comprehensive local surveillance, we were able to identify several potential GAS transmission events. Further analysis – including whole genome sequencing on index and PTE isolates – is needed to better define transmission events. Disclosures Jonathon C. McNeil, MD, Nabriva (Research Grant or Support, I serve as the site investigator on a multicenter clinical trial sponsored by Nabriva)

scholarly journals Canada-Wide Epidemic of emm74 Group A Streptococcus Invasive Disease

2018 ◽  
Vol 5 (5) ◽  
Author(s):  
Sarah Teatero ◽  
Allison McGeer ◽  
Gregory J Tyrrell ◽  
Linda Hoang ◽  
Hanan Smadi ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Invasive Disease ◽  
Drug Usage ◽  
Rare Type ◽  
Invasive Group ◽  
Intravenous Drug Usage ◽  
Clinical Data Analysis ◽  
Invasive Infections ◽  
Group A ◽  
Canadian Provinces

Abstract Background The number of invasive group A Streptococcus (iGAS) infections due to hitherto extremely rare type emm74 strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an emm74 clone that recently emerged and expanded explosively. Methods We analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the emm74 strains responsible for these invasive infections country-wide. Results Genome analysis showed that highly clonal emm74 strains, genetically different from emm74 organisms previously circulating in Canada, were responsible for a country-wide epidemic of >160 invasive disease cases. The emerging clone belonged to multilocus sequence typing ST120. The analysis also revealed dissemination patterns of emm74 subclonal lineages across Canadian provinces. Clinical data analysis indicated that the emm74 epidemic disproportionally affected middle-aged or older male individuals. Homelessness, alcohol abuse, and intravenous drug usage were significantly associated with invasive emm74 infections. Conclusions In a period of 20 months, an emm74 GAS clone emerged and rapidly spread across several Canadian provinces located more than 4500 km apart, causing invasive infections primarily among disadvantaged persons.

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