Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.114
Filtrar
1.
Methods Mol Biol ; 2449: 299-324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507269

RESUMO

The paradigm shift associated with the introduction of the pan-genome concept has drawn the attention from singular reference genomes toward the actual sequence diversity within organism populations, strain collections, clades, etc. A single genome is no longer sufficient to describe bacteria of interest, but instead, the genomic repertoire of all existing strains is the key to the metabolic, evolutionary, or pathogenic potential of a species. The classification of orthologous genes derived from a collection of taxonomically related genome sequences is central to bacterial pan-genome computational analysis. In this work, we present a review of methods for computing pan-genome gene clusters including their comparative analysis for the case of Streptococcus pyogenes strain genomes. We exhaustively scanned the parametrization space of the homologue searching procedures and find optimal parameters (sequence identity (60%) and coverage (50-60%) in the pairwise alignment) for the orthologous clustering of gene sequences. We find that the sequence identity threshold influences the number of gene families ~3 times stronger than the sequence coverage threshold.


Assuntos
Genoma Bacteriano , Streptococcus pyogenes , Análise por Conglomerados , Genômica/métodos , Família Multigênica , Filogenia , Streptococcus pyogenes/genética
2.
Nat Commun ; 13(1): 2469, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513429

RESUMO

Combinatorial CRISPR technologies have emerged as a transformative approach to systematically probe genetic interactions and dependencies of redundant gene pairs. However, the performance of different functional genomic tools for multiplexing sgRNAs vary widely. Here, we generate and benchmark ten distinct pooled combinatorial CRISPR libraries targeting paralog pairs to optimize digenic knockout screens. Libraries composed of dual Streptococcus pyogenes Cas9 (spCas9), orthogonal spCas9 and Staphylococcus aureus (saCas9), and enhanced Cas12a from Acidaminococcus were evaluated. We demonstrate a combination of alternative tracrRNA sequences from spCas9 consistently show superior effect size and positional balance between the sgRNAs as a robust combinatorial approach to profile genetic interactions of multiple genes.


Assuntos
Acidaminococcus , Sistemas CRISPR-Cas , Acidaminococcus/genética , Sistemas CRISPR-Cas/genética , RNA Guia/genética , Staphylococcus aureus/genética , Streptococcus pyogenes/genética
3.
BMC Med ; 20(1): 173, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35505341

RESUMO

BACKGROUND: Necrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) or Streptococcus pyogenes (mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive. METHODS: In this study, we built interactomes at both the population and individual levels consisting of host-pathogen interactions inferred from dual RNA-Seq gene transcriptomic profiles of the biopsies from NSTI patients. RESULTS: NSTI type-specific responses in the host were uncovered. The S. pyogenes mono-microbial subnetwork was enriched with host genes annotated with involved in cytokine production and regulation of response to stress. The polymicrobial network consisted of several significant associations between different species (S. pyogenes, Porphyromonas asaccharolytica and Escherichia coli) and host genes. The host genes associated with S. pyogenes in this subnetwork were characterised by cellular response to cytokines. We further found several virulence factors including hyaluronan synthase, Sic1, Isp, SagF, SagG, ScfAB-operon, Fba and genes upstream and downstream of EndoS along with bacterial housekeeping genes interacting with the human stress and immune response in various subnetworks between host and pathogen. CONCLUSIONS: At the population level, we found aetiology-dependent responses showing the potential modes of entry and immune evasion strategies employed by S. pyogenes, congruent with general cellular processes such as differentiation and proliferation. After stratifying the patients based on the subject-specific networks to study the patient-specific response, we observed different patient groups with different collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate differing modes of entry and immune evasion for different bacteria in relationship to the patients' phenotype.


Assuntos
Coinfecção , Infecções dos Tecidos Moles , Infecções Estreptocócicas , Coinfecção/genética , Humanos , Infecções dos Tecidos Moles/genética , Infecções dos Tecidos Moles/microbiologia , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Fatores de Virulência/genética
4.
BMC Pediatr ; 22(1): 227, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473515

RESUMO

BACKGROUND: Group A Streptococcus has been recognized as an important human pathogen and it remains among the top ten causes of mortality from an infectious disease. Group A Streptococcus throat carriage plays an important role in the development of infection and transmission to contacts. In Ethiopia, there is little information about screening of children for group A Streptococcus carriage. OBJECTIVE: This study was aimed to assess the magnitude of throat carriage, associated factors, and antimicrobial susceptibility pattern of group A Streptococcus among healthy school children in Jigjiga city, Eastern Ethiopia from 12 April to 27 May 2021. METHOD: A cross-sectional study was conducted enrolled by simple random sampling. Data on socio-demographic and related characteristics were gathered using pretested structured questionnaire. The throat sample was collected from 462 healthy school children and immediately transported to Jigjiga University Sultan Sheik Hassan referral hospital laboratory for investigation. Identification of group A Streptococcus was done by colony characterstics, gram staining, catalase negativity, bacitracin sensitivity, and Pyrrolidonyl arylamidase tests. Antibiotic susceptibility test was done on Muller-Hinton agar containing 5% sheep blood by modified Kirby-Bauer disc diffusion method. The data were coded, cleaned, and entered onto EpiData Version 3.1 then exported to SPSS version 26.0 for analysis. Bivariate and multivariable logistic regression through adjusted odds ratio (AOR) was used to determine the relationship between culture-positivity rates of GAS and predictor variables. A p-value < 0.05 was taken as statistically significant on multivariable analysis. RESULTS: The overall prevalence of group A Streptococcus throat culture rate was 10.6% (95%CI; 8.1%-13.7%). Previous family member who had a sore throat, children living with larger families (more than 11 members), and children living with non-immediate families were significantly associated with culture-positivity rates of GAS. Children who live with a family member with a sore throat compared with those who lived with in a family with no history of sore throat (AOR = 2.51; 95%CI 1.09-5.73), children who live with a large family comared to children living in families with less members (AOR = 4.64; 95% CI 1.53-14.1), and children who live with non-immediate families compared to children living with their mothers (AOR = 3.65; 95% CI 1.39 - 9.61), showed significant association with group A Streptococcus carriage rate. Resistance to all other antibiotics tested was low (< 5%). Multidrug resistance was found in 4.1% of isolates. CONCLUSION: The present study showed 10.6% throat carriage of group A Streptococcus. Family member with a sore throat, having a large family, and living with non-immediate families have all been identified as independent predictors of carriage prevalence.


Assuntos
Faringite , Faringe , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Portador Sadio/epidemiologia , Criança , Estudos Transversais , Etiópia/epidemiologia , Humanos , Faringite/tratamento farmacológico , Faringite/epidemiologia , Ovinos , Streptococcus pyogenes
5.
MMW Fortschr Med ; 164(Suppl 1): 10, 2022 04.
Artigo em Alemão | MEDLINE | ID: mdl-35359279
6.
BMJ Open ; 12(4): e057296, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35387825

RESUMO

INTRODUCTION: Group A ß-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune diseases acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Aboriginal and Torres Strait Islander peoples in Australia have the highest rates of ARF and RHD in the world. Despite this, the contemporaneous prevalence and incidence of GAS pharyngitis and impetigo in remote Australia remains unknown. To address this, we have designed a prospective surveillance study of GAS pharyngitis and impetigo to collect coincident contemporary evidence to inform and enhance primary prevention strategies for ARF. METHODS AND ANALYSIS: The Missing Piece Study aims to document the epidemiology of GAS pharyngitis and impetigo through collection of clinical, serological, microbiological and bacterial genomic data among remote-living Australian children. The study comprises two components: (1) screening of all children at school for GAS pharyngitis and impetigo up to three times a year and (2) weekly active surveillance visits to detect new cases of pharyngitis and impetigo. Environmental swabbing in remote schools will be included, to inform environmental health interventions. In addition, the application of new diagnostic technologies, microbiome analysis and bacterial genomic evaluations will enhance primary prevention strategies, having direct bearing on clinical care, vaccine development and surveillance for vaccine clinical trials. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Western Australian Aboriginal Health Ethics Committee (Ref: 892) and Human Research Ethics Committee of the University of Western Australia (Ref: RA/4/20/5101). Study findings will be shared with community members, teachers and children at participating schools, together with academic and medical services. Sharing findings in an appropriate manner is important and will be done in a suitable way which includes plain language summaries and presentations. Finally, findings and updates will also be disseminated to collaborators, researchers and health planners through peer-reviewed journal publications.


Assuntos
Serviços de Saúde do Indígena , Impetigo , Faringite , Febre Reumática , Cardiopatia Reumática , Infecções Estreptocócicas , Austrália/epidemiologia , Criança , Humanos , Impetigo/epidemiologia , Faringite/tratamento farmacológico , Faringite/epidemiologia , Estudos Prospectivos , Febre Reumática/epidemiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus pyogenes , Austrália Ocidental/epidemiologia
8.
Emerg Infect Dis ; 28(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35451366

RESUMO

Healthcare-associated invasive group A Streptococcus (iGAS) outbreaks are common worldwide, but only England has reported outbreaks associated with home healthcare (HHC). We describe 10 outbreaks during 2018-2019 in England. A total of 96 iGAS cases (range 2-39 per outbreak) and 28 deaths (case-fatality rate 29%) occurred. Outbreak duration ranged from 3-517 days; median time between sequential cases was 20.5 days (range 1-225 days). Outbreak identification was difficult, but emm typing and whole-genome sequencing improved detection. Network analyses indicated multiple potential transmission routes. Screening of 366 HHC workers from 9 outbreaks identified group A Streptococcus carriage in just 1 worker. Outbreak control required multiple interventions, including improved infection control, equipment decontamination, and antimicrobial prophylaxis for staff. Transmission routes and effective interventions are not yet clear, and iGAS outbreaks likely are underrecognized. To improve patient safety and reduce deaths, public health agencies should be aware of HHC-associated iGAS.


Assuntos
Infecção Hospitalar , Infecções Estreptocócicas , Infecção Hospitalar/epidemiologia , Atenção à Saúde , Surtos de Doenças/prevenção & controle , Inglaterra/epidemiologia , Humanos , Streptococcus pyogenes/genética
9.
Cell Host Microbe ; 30(4): 410-412, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35421330

RESUMO

The gasdermin family of cell death executor proteins are activated by different proteases under different physiological conditions. A recent study by Deng et al. in Nature revealed that the cysteine protease SpeB from the human pathogen Streptococcus pyogenes directly cleaves and activates Gasdermin A to induce pyroptosis in skin cells.


Assuntos
Piroptose , Streptococcus pyogenes , Morte Celular , Humanos , Peptídeo Hidrolases
10.
Int J Pharm ; 617: 121614, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35245637

RESUMO

Currently there is no approved vaccine to prevent and/or treat group A Streptococcus (GAS) infection. With increasing reports of GAS antibiotic resistance, vaccine adjuvants and targeted delivery systems which induce a strong immune response are a widely acknowledged unmet need. Through extensive structure-activity studies, we investigated a cyclic decapeptide physically mixed with a GAS B cell peptide epitope (J8), a universal T helper epitope (PADRE), and different synthetic lipidic moieties as a conceivable self-adjuvanting GAS vaccine. We explored the structure (orientation)-relationship of the chemically-conjugated B cell epitope and T helper epitope peptide as part of this physically-mixed vaccine. Following in vivo assessment in mice, these cyclic lipopeptide vaccines showed successful induction of J8-specific systemic IgG antibodies when administered subcutaneously without additional adjuvant. Interestingly, an exposed C-terminus of the GAS B cell epitope and a 16-carbon alpha-amino fatty acid lipid was required for strong immunoreactivity, capable of effectively opsonising multiple strains of clinically-isolated GAS bacteria. Physicochemical assessment proved the alpha helix structure of the GAS B cell epitope was retained, impacting particle self-assembly and vaccine immunoreactivity. This study showed the capability for a self-adjuvanting cyclic delivery system to act as a vehicle for the delivery of GAS peptide antigens to treat GAS infection.


Assuntos
Streptococcus pyogenes , Vacinas , Adjuvantes Imunológicos/farmacologia , Animais , Lipídeos/química , Camundongos , Peptídeos Cíclicos/farmacologia , Relação Estrutura-Atividade , Vacinas/farmacologia , Vacinas de Subunidades
11.
Infect Genet Evol ; 100: 105259, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35231667

RESUMO

Streptococcus pyogenes is a root cause of human infection like pharyngitis, tonsillitis, scarlet fever, impetigo, and respiratory tract infections. About 11 million individuals in the US suffer from pharyngitis every year. Unfortunately, no vaccine against S. pyogenes is available yet. The purpose of this study is to create a multiepitope-based subunit vaccine (MEBSV) targeting S. pyogenes top four highly antigenic proteins by using a combination of immunological techniques and molecular docking to tackle term group A streptococcal (GAS) infections. T-cell (HTL & CTL), B-cell, and IFN-γ of target proteins were forecasted and epitopes having high antigenic properties being selected for subsequent research. For designing of final vaccine, 5LBL, 9CTL, and 4HTL epitopes were joined by the KK, AAY, and GPGPG linkers. To enhance the immune response, the N-end of the vaccine was linked by adjuvant (Cholera enterotoxin subunit B) with a linker named EAAAK. With the addition of adjuvants and linkers, the construct size was 421 amino acids. IFN-γ and B-cell epitopes illustrate that the modeled construct is optimized for cell-mediated immune or humoral responses. The developed MEBSV structure was assessed to be highly antigenic, non-toxic, and non-allergenic. Moreover, disulphide engineering further enhanced the stability of the final vaccine protein. Molecular docking of the MEBSV with toll-like receptor 4 (TLR4) was conducted to check the vaccine's compatibility with the receptor. Besides, in-silico cloning has been carried out for credibility validation and proper expression of vaccine construct. These findings suggested that the multi-epitope vaccine produced might be a potential immunogenic against Group A streptococcus infections but further experimental testing is required to validate this study.


Assuntos
Faringite , Vacinologia , Biologia Computacional , Epitopos de Linfócito B , Epitopos de Linfócito T , Humanos , Simulação de Acoplamento Molecular , Proteoma , Streptococcus pyogenes/genética , Vacinas de Subunidades
12.
Nat Microbiol ; 7(4): 530-541, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35314780

RESUMO

CRISPR-Cas systems store fragments of foreign DNA, called spacers, as immunological recordings used to combat future infections. Of the many spacers stored in a CRISPR array, the most recent are known to be prioritized for immune defence. However, the underlying mechanism remains unclear. Here we show that the leader region upstream of CRISPR arrays in CRISPR-Cas9 systems enhances CRISPR RNA (crRNA) processing from the newest spacer, prioritizing defence against the matching invader. Using the CRISPR-Cas9 system from Streptococcus pyogenes as a model, we found that the transcribed leader interacts with the conserved repeats bordering the newest spacer. The resulting interaction promotes transactivating crRNA (tracrRNA) hybridization with the second of the two repeats, accelerating crRNA processing. Accordingly, disruption of this structure reduces the abundance of the associated crRNA and immune defence against targeted plasmids and bacteriophages. Beyond the S. pyogenes system, bioinformatics analyses revealed that leader-repeat structures appear across CRISPR-Cas9 systems. CRISPR-Cas systems thus possess an RNA-based mechanism to prioritize defence against the most recently encountered invaders.


Assuntos
Bacteriófagos , Proteínas Associadas a CRISPR , Bacteriófagos/genética , Bacteriófagos/metabolismo , Proteínas Associadas a CRISPR/metabolismo , Sistemas CRISPR-Cas , RNA/genética , Streptococcus pyogenes/genética , Streptococcus pyogenes/metabolismo
13.
PLoS One ; 17(2): e0263792, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35176056

RESUMO

Recently a technique based on the interaction between adhesion proteins extracted from Streptococcus pyogenes, known as SpyRing, has been widely used to improve the thermal resilience of enzymes, the assembly of biostructures, cancer cell recognition and other fields. It was believed that the covalent cyclization of protein skeleton caused by SpyRing reduces the conformational entropy of biological structure and improves its rigidity, thus improving the thermal resilience of the target enzyme. However, the effects of SpyTag/ SpyCatcher interaction with this enzyme are poorly understood, and their regulation of enzyme properties remains unclear. Here, for simplicity, we took the single domain enzyme lichenase from Bacillus subtilis 168 as an example, studied the interface interactions in the SpyRing by molecular dynamics simulations, and examined the effects of the changes of electrostatic interaction and van der Waals interaction on the thermal resilience of target enzyme. The simulations showed that the interface between SpyTag/SpyCatcher and the target enzyme is different from that found by geometric matching method and highlighted key mutations at the interface that might have effect on the thermal resilience of the enzyme. Our calculations highlighted interfacial interactions between enzyme and SpyTag/SpyCatcher, which might be useful in rational designs of the SpyRing.


Assuntos
Bacillus subtilis/enzimologia , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Temperatura Alta , Simulação de Dinâmica Molecular , Streptococcus pyogenes/enzimologia , Ciclização , Concentração de Íons de Hidrogênio
14.
J Med Case Rep ; 16(1): 55, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35144688

RESUMO

BACKGROUND: Group A streptococcus infection during pregnancy can be concerning. It may cause toxic shock syndrome, which can be fatal. Here, we report a rare case of a pregnant woman who developed infectious sacroiliitis due to group A streptococcus infection. To the best of our knowledge, this case is the first of its kind to be reported. CASE PRESENTATION: A 32-year-old multiparous Japanese woman presented with fever and right buttock pain at 28 weeks of gestation. Based on our clinical findings and investigations, she was diagnosed with group A streptococcus bacteremia and infectious sacroiliitis caused by group A streptococcus. A cardiotocography performed to assess the fetal status showed fetal tachycardia. To prevent the patient from progressing to toxic shock syndrome caused by group A streptococcus, we performed an emergency cesarean section. The patient and her infant had a good course after the cesarean section. CONCLUSION: A pregnant woman diagnosed with group A streptococcus infection needs to be monitored closely because a timely decision to deliver the fetus before rapid deterioration to toxic shock syndrome is crucial.


Assuntos
Complicações Infecciosas na Gravidez , Sacroileíte , Choque Séptico , Infecções Estreptocócicas , Adulto , Cesárea , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Sacroileíte/diagnóstico por imagem , Sacroileíte/tratamento farmacológico , Choque Séptico/diagnóstico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes
15.
Ann Lab Med ; 42(4): 438-446, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35177564

RESUMO

BACKGROUND: Few studies have investigated the invasiveness of Streptococcus pyogenes based on whole-genome sequencing (WGS). Using WGS, we determined the genomic features associated with invasiveness of S. pyogenes strains in Korea. METHODS: Forty-five S. pyogenes strains from 1997, 2006, and 2017, including common emm types, were selected from the repository at Gyeongsang National University Hospital in Korea. In addition, 48 S. pyogenes strains were randomly selected depending on their invasiveness between 1997 and 2017 to evaluate the genetic evolution and the associations between invasiveness and genetic profiles. Using WGS datasets, we conducted virulence-associated DNA sequence determination, emm genotyping, multi-locus sequence typing (MLST), and superantigen gene profiling. RESULTS: In total, 87 strains were included in this study. There were no significant differences in the genomic features throughout the study periods. Four genes, csn1, ispE, nisK, and citC, were detected only in invasive strains. There was a significant association between invasiveness and emm cluster type A-C3, including, emm1.0, emm1.18, emm1.3, and emm1.76 (P<0.05). The predominant emm1 lineage belonged to ST28. There were no associations between invasiveness and superantigen gene profiles. CONCLUSIONS: This is the first study using WGS datasets of S. pyogenes strains collected between 1997 and 2017 in Korea. Streptococcal invasiveness is associated with the presence of csn1, ispE, nisK, and citC. The emm1 lineage and ST28 clone are explicitly associated with invasiveness, whereas genomic features remained stable over the 20-year period.


Assuntos
Infecções Estreptocócicas , Streptococcus pyogenes , Antígenos de Bactérias/genética , Genômica , Genótipo , Humanos , Tipagem de Sequências Multilocus , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/genética
16.
Immunol Cell Biol ; 100(3): 174-185, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35124861

RESUMO

The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS virulence, the pilus has become an attractive target for vaccine development. While current research mainly focuses on pilus function and its potential as a vaccine component, there is a lack of knowledge on how the host immune system recognizes and responds to this abundant surface structure. Here we show that both assembled GAS pili and individual pilus proteins induce a potent release of the proinflammatory cytokines tumor necrosis factor and interleukin-8. We further show that the surface-exposed backbone pilin and ancillary pilin 1 subunits are Toll-like receptor 2 (TLR2) agonists. Using reporter cell lines coexpressing human TLR2 in combination with either TLR1 or TLR6, we determined that activation was mediated by the TLR2/TLR6 heterodimer. Finally, we used solid-phase and flow cytometry binding assays to illustrate a direct interaction between the pilus subunits and TLR2. These results provide further support for the suitability of the pilus as a vaccine component and opens potential avenues for using GAS pili as an adjuvant or immune-modulation agent.


Assuntos
Proteínas de Fímbrias , Streptococcus pyogenes , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Fímbrias/metabolismo , Humanos , Imunidade Inata , Streptococcus pyogenes/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 6 Toll-Like/metabolismo
18.
Nat Commun ; 13(1): 1053, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35217666

RESUMO

Preexisting immunity against Cas9 proteins in humans represents a safety risk for CRISPR-Cas9 technologies. However, it is unclear to what extent preexisting Cas9 immunity is relevant to the eye as it is targeted for early in vivo CRISPR-Cas9 clinical trials. While the eye lacks T-cells, it contains antibodies, cytokines, and resident immune cells. Although precise mechanisms are unclear, intraocular inflammation remains a major cause of vision loss. Here, we used immunoglobulin isotyping and ELISA platforms to profile antibodies in serum and vitreous fluid biopsies from human adult subjects and Cas9-immunized mice. We observed high prevalence of preexisting Cas9-reactive antibodies in serum but not in the eye. However, we detected intraocular antibodies reactive to S. pyogenes-derived Cas9 after S. pyogenes intraocular infection. Our data suggest that serum antibody concentration may determine whether specific intraocular antibodies develop, but preexisting immunity to Cas9 may represent a lower risk in human eyes than systemically.


Assuntos
Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Animais , Anticorpos/metabolismo , Proteína 9 Associada à CRISPR/metabolismo , Humanos , Camundongos , Streptococcus pyogenes/metabolismo , Linfócitos T
19.
Pediatr Infect Dis J ; 41(5): 405-410, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213863

RESUMO

BACKGROUND: Group A ß-hemolytic streptococcus (GABHS) is a leading pathogen worldwide and post-streptococcal sequelae is a major cause of morbidity and mortality in resource-limited countries. The M protein (coded by the emm gene) is a key virulence factor and a component of GABHS vaccine candidates. As data on BHS in Central Africa are scarce, antibiotic resistance, emm diversity and potential vaccine coverage were investigated. METHODS: In a prospective cross-sectional study, 1014 Gabonese were screened for streptococcal throat carriage, tonsillopharyngitis and pyoderma by throat and skin smear tests. All BHS were isolated, species were identified and analysis of antibiotic resistance, emm types and emm clusters was performed. RESULTS: One hundred sixty-five BHS were detected, comprising 76 GABHS, 36 group C ß-hemolytic streptococcus (GCBHS) and 53 group G ß-hemolytic streptococcus (GGBHS) in 140 carrier, 9 tonsillopharyngitis and 16 pyoderma isolates. Eighty percentage of GABHS, 78% of GCBHS and 79% of GGBHS were tetracycline resistant. Forty-six emm types were identified. GABHS emm58, emm65 and emm81 were most prevalent (26%). Emm diversity of GABHS was the highest, GCBHS and GGBHS were less divers. Every second GABHS, every third GCBHS and every tenth GGBHS carrier was colonized with emm types detected in tonsillopharyngitis or pyoderma isolates. CONCLUSIONS: Tetracycline resistance and emm type diversity was high among BHS carriers in Gabon with a potential coverage of 58% by the 30-valent GABHS vaccine. A relevant overlap of carrier emm types with emm types found in tonsillopharyngitis and pyoderma characterizes a shared pool of circulating BHS strains.


Assuntos
Faringite , Pioderma , Infecções Estreptocócicas , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Estudos Transversais , Gabão/epidemiologia , Humanos , Faringite/epidemiologia , Estudos Prospectivos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus pyogenes , Resistência a Tetraciclina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...