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1.
BMJ Case Rep ; 14(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563670

RESUMO

Cerebral vasculitis is a serious complication of bacterial meningitis that can cause significant morbidity and mortality due to stroke. Currently, there are no treatment guidelines or safety and efficacy studies on the management of cerebral vasculitis in this context. Herein, we report a case of a previously well 11-year-old girl who presented with acute otitis media that progressed to mastoiditis and fulminant meningitis. Group A Streptococcus was found in blood and ear-fluid cultures (lumbar puncture was unsuccessful). Her decreased level of consciousness persisted despite appropriate antimicrobial treatment, and repeat MRI revealed extensive large vessel cerebral vasculitis. Based on expert opinion and a presumed inflammatory mechanism, her cerebral vasculitis was treated with 7 days of pulse intravenous methylprednisolone followed by oral prednisone taper. She was also treated with intravenous heparin. Following these therapies, she improved clinically and radiographically with no adverse events. She continues to undergo rehabilitation with improvement.


Assuntos
Antibacterianos/administração & dosagem , Heparina/administração & dosagem , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Vasculite do Sistema Nervoso Central/diagnóstico , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Criança , Diagnóstico Diferencial , Diagnóstico por Imagem , Quimioterapia Combinada , Feminino , Humanos , Meningites Bacterianas/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Vasculite do Sistema Nervoso Central/microbiologia
2.
Nucleic Acids Res ; 49(2): 1173-1198, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33398349

RESUMO

RNA-guided nucleases (RGNs) based on CRISPR systems permit installing short and large edits within eukaryotic genomes. However, precise genome editing is often hindered due to nuclease off-target activities and the multiple-copy character of the vast majority of chromosomal sequences. Dual nicking RGNs and high-specificity RGNs both exhibit low off-target activities. Here, we report that high-specificity Cas9 nucleases are convertible into nicking Cas9D10A variants whose precision is superior to that of the commonly used Cas9D10A nickase. Dual nicking RGNs based on a selected group of these Cas9D10A variants can yield gene knockouts and gene knock-ins at frequencies similar to or higher than those achieved by their conventional counterparts. Moreover, high-specificity dual nicking RGNs are capable of distinguishing highly similar sequences by 'tiptoeing' over pre-existing single base-pair polymorphisms. Finally, high-specificity RNA-guided nicking complexes generally preserve genomic integrity, as demonstrated by unbiased genome-wide high-throughput sequencing assays. Thus, in addition to substantially enlarging the Cas9 nickase toolkit, we demonstrate the feasibility in expanding the range and precision of DNA knockout and knock-in procedures. The herein introduced tools and multi-tier high-specificity genome editing strategies might be particularly beneficial whenever predictability and/or safety of genetic manipulations are paramount.


Assuntos
Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas , Desoxirribonuclease I/metabolismo , Edição de Genes/métodos , Proteínas de Bactérias/genética , Sequência de Bases , Proteína 9 Associada à CRISPR/genética , Células Clonais , Desoxirribonuclease I/genética , Técnicas de Introdução de Genes , Técnicas de Inativação de Genes , Genes Reporter , Técnicas de Genotipagem , Células HEK293 , Células HeLa , Heterocromatina/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Células-Tronco Pluripotentes Induzidas , Polimorfismo Genético , RNA Guia/genética , Proteínas Recombinantes/metabolismo , Streptococcus pyogenes/enzimologia , Especificidade por Substrato , Transfecção
3.
4.
Nat Commun ; 12(1): 349, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441553

RESUMO

The widely used Streptococcus pyogenes Cas9 (SpCas9) nuclease derives its DNA targeting specificity from protein-DNA contacts with protospacer adjacent motif (PAM) sequences, in addition to base-pairing interactions between its guide RNA and target DNA. Previous reports have established that the PAM specificity of SpCas9 can be altered via positive selection procedures for directed evolution or other protein engineering strategies. Here we exploit in vivo directed evolution systems that incorporate simultaneous positive and negative selection to evolve SpCas9 variants with commensurate or improved activity on NAG PAMs relative to wild type and reduced activity on NGG PAMs, particularly YGG PAMs. We also show that the PAM preferences of available evolutionary intermediates effectively determine whether similar counterselection PAMs elicit different selection stringencies, and demonstrate that negative selection can be specifically increased in a yeast selection system through the fusion of compensatory zinc fingers to SpCas9.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas , DNA/metabolismo , Edição de Genes/métodos , RNA Guia/metabolismo , Streptococcus pyogenes/metabolismo , Sequência de Aminoácidos , Proteína 9 Associada à CRISPR/genética , Linhagem Celular Tumoral , DNA/química , DNA/genética , Evolução Molecular Direcionada/métodos , Humanos , Mutação , Conformação de Ácido Nucleico , Motivos de Nucleotídeos/genética , Engenharia de Proteínas/métodos , RNA Guia/genética , Streptococcus pyogenes/genética , Especificidade por Substrato
5.
Nat Commun ; 12(1): 691, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514730

RESUMO

Methyl-specific isotope labeling is a powerful tool to study the structure, dynamics and interactions of large proteins and protein complexes by solution-state NMR. However, widespread applications of this methodology have been limited by challenges in obtaining confident resonance assignments. Here, we present Methyl Assignments Using Satisfiability (MAUS), leveraging Nuclear Overhauser Effect cross-peak data, peak residue type classification and a known 3D structure or structural model to provide robust resonance assignments consistent with all the experimental inputs. Using data recorded for targets with known assignments in the 10-45 kDa size range, MAUS outperforms existing methods by up to 25,000 times in speed while maintaining 100% accuracy. We derive de novo assignments for multiple Cas9 nuclease domains, demonstrating that the methyl resonances of multi-domain proteins can be assigned accurately in a matter of days, while reducing biases introduced by manual pre-processing of the raw NOE data. MAUS is available through an online web-server.


Assuntos
Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular/métodos , Algoritmos , Proteína 9 Associada à CRISPR/ultraestrutura , Isótopos de Carbono , Interleucina-2/química , Interleucina-2/isolamento & purificação , Marcação por Isótopo/métodos , Ressonância Magnética Nuclear Biomolecular/instrumentação , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/ultraestrutura , Streptococcus pyogenes/enzimologia , Trítio
6.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462043

RESUMO

Group A streptococcus (GAS) causes a wide variety of infections in the paediatric population, ranging from pharyngitis to rare but severe invasive diseases, such as bacterial arthritis and osteomyelitis. Dental neglect is a type of child neglect in which caregivers fail to provide adequate care and treatment for dental diseases. This results in poor oral hygiene and can lead to complications including sepsis. We report the case of a 4-year-old boy, suffering from child neglect, presenting with GAS pharyngitis and subsequent bacterial arthritis in the right ankle, osteomyelitis in the right talus and abscess in the right calcaneus. He was first treated with penicillin, which was changed to clindamycin because of a suspected drug-induced rash. He was discharged after 6 weeks of intravenous therapy when symptoms had resolved and inflammatory markers were within the normal range. The case highlights that dental neglect may present a risk for subsequent invasive infections.


Assuntos
Artrite Infecciosa/microbiologia , Higiene Bucal , Osteomielite/microbiologia , Faringite/microbiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/isolamento & purificação , Artrite Infecciosa/diagnóstico , Pré-Escolar , Humanos , Masculino , Osteomielite/diagnóstico , Faringite/diagnóstico
7.
BMJ Case Rep ; 14(1)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495174

RESUMO

Constrictive pericarditis is a relatively uncommon form of cardiac failure and presents due to scarring and consequent loss of the normal elasticity of the pericardial sac. This results in abnormal/limited ventricular filling and symptoms of heart failure. The aetiology is varied, from infective causes to idiopathic causes, or can manifest after cardiothoracic surgery. This case involves a 46-year-old man presenting with acute group A beta haemolytic streptococcus infection, and over the subsequent 6 months develops constrictive pericarditis due to what is believed to be a rheumatic aetiology. The patient subsequently underwent pericardiectomy and had restoration of normal filling dynamics confirmed on follow-up echocardiography. This case provides a subject matter for the review of the features of constrictive pericarditis and its investigation and management. This case is that it highlights the fact that pericarditis is not a benign condition. Emerging evidence suggests that pericarditis is due to a failure in inflammatory regulatory mechanisms, and patients suffering this condition have a preponderance to 'autoinflammation'. Pericarditis should be recognised early and treated fully with anti-inflammatory agents.


Assuntos
Bacteriemia/diagnóstico , Pericardite Constritiva/diagnóstico , Cardiopatia Reumática/diagnóstico , Infecções Estreptocócicas/diagnóstico , Antibacterianos/uso terapêutico , Antiestreptolisina/imunologia , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Hemocultura , Proteína C-Reativa/imunologia , Cateterismo Cardíaco , Ceftriaxona/uso terapêutico , Eletrocardiografia , Hospitalização , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pericardiectomia , Pericardite Constritiva/etiologia , Pericardite Constritiva/fisiopatologia , Pericardite Constritiva/cirurgia , Combinação Piperacilina e Tazobactam/uso terapêutico , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/cirurgia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Pressão Ventricular
8.
Mol Cell ; 81(2): 226-238.e5, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33378644

RESUMO

Currently, either highly multiplexed genetic manipulations can be delivered to mammalian cells all at once or extensive engineering of gene regulatory sequences can be used to conditionally activate a few manipulations. Here, we provide proof of principle for a new system enabling multiple genetic manipulations to be executed as a preprogrammed cascade of events. The system leverages the programmability of the S. pyogenes Cas9 and is based on flexible arrangements of individual modules of activity. The basic module consists of an inactive single-guide RNA (sgRNA)-like component that is converted to an active state through the effects of another sgRNA. Modules can be arranged to bring about an algorithmic program of sequential genetic manipulations without the need for engineering cell-type-specific promoters or gene regulatory sequences. With the expanding diversity of available tools that use spCas9, this sgRNA-based system provides multiple levels of interfacing with mammalian cell biology.


Assuntos
Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes/métodos , RNA Guia/genética , Animais , Pareamento de Bases , Sequência de Bases , Proteína 9 Associada à CRISPR/metabolismo , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Conformação de Ácido Nucleico , Plasmídeos/química , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , RNA Guia/química , RNA Guia/metabolismo , Streptococcus pyogenes/química , Streptococcus pyogenes/enzimologia
9.
Autoimmun Rev ; 20(2): 102740, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33333234

RESUMO

Rheumatic heart disease (RHD) is a serious and long-term consequence of acute rheumatic fever (ARF), an autoimmune sequela of a mucosal infection by Streptococcus pyogenes (Group A Streptococcus, Strep A). The pathogenesis of ARF and RHD is complex and not fully understood but involves host and bacterial factors, molecular mimicry, and aberrant host innate and adaptive immune responses that result in loss of self-tolerance and subsequent cross-reactivity with host tissues. RHD is entirely preventable yet claims an estimated 320 000 lives annually. The major burden of disease is carried by developing nations and Indigenous populations within developed nations, including Australia. This review will focus on the epidemiology, pathogenesis and treatment of ARF and RHD in Australia, where: streptococcal pyoderma, rather than streptococcal pharyngitis, and Group C and Group G Streptococcus, have been implicated as antecedents to ARF; the rates of RHD in remote Indigenous communities are persistently among the highest in the world; government register-based programs coordinate disease screening and delivery of prophylaxis with variable success; and researchers are making significant progress in the development of a broad-spectrum vaccine against Strep A.


Assuntos
Febre Reumática , Cardiopatia Reumática , Infecções Estreptocócicas , Austrália , Humanos , Pesquisa , Febre Reumática/diagnóstico , Febre Reumática/epidemiologia , Febre Reumática/terapia , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/terapia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes
10.
Ann Agric Environ Med ; 27(4): 540-543, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33356058

RESUMO

INTRODUCTION: The role of fungi in infections in immunocompromised patients is a growing problem in both diagnosis and treatment. Candida species are the most common cause of fungal, endogenous endophthalmitis and infections of the cornea. CASE STUDY: A patient was admitted to hospital due to acute inflammation of the tissue of the left orbit, 1.5 years after the corneal penetrating transplantation of the left eye with intracapsular extraction of lens and simultaneous anterior vitrectomy. The microbiological system identified: Streptococcus pyogenes, Staphylococcus aureus, and Candida glabrata in the patient. CONCLUSIONS: The factors conducive to fungal infections are: patient's old age, immune disorders and diabetes, as well as the presence of a necrotic tissue or a foreign body. All these parameters were met in this case. Only antibiotic therapy and long-term antifungal therapy, together with surgical debridement of the site of the ongoing infection produces clinical effects in such severe cases.


Assuntos
Antifúngicos/uso terapêutico , Candida glabrata/isolamento & purificação , Candidíase/diagnóstico , Desbridamento , Infecções Oculares Fúngicas/diagnóstico , Panoftalmite/diagnóstico , Idoso , Antibacterianos/uso terapêutico , Candidíase/microbiologia , Candidíase/fisiopatologia , Infecções Oculares Fúngicas/microbiologia , Feminino , Humanos , Panoftalmite/microbiologia , Polônia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/isolamento & purificação , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/terapia , Streptococcus pyogenes/isolamento & purificação , Resultado do Tratamento
11.
J Vis Exp ; (166)2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33369608

RESUMO

The bacterial Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Streptococcus pyogenes CRISPR-associated protein (Cas) system has been harnessed by researchers to study important biologically relevant problems. The unparalleled power of the CRISPR/Cas genome editing method allows researchers to precisely edit any locus of their choosing, thereby facilitating an increased understanding of gene function. Several methods for editing the C. elegans genome by CRISPR/Cas9 have been described previously. Here, we discuss and demonstrate a method which utilizes in vitro assembled ribonucleoprotein complexes and the dpy-10 co-CRISPR marker for screening. Specifically, in this article, we go through the step-by-step process of introducing premature stop codons into the C. elegans rbm-3.2 gene by homology-directed repair using this method of CRISPR/Cas9 editing. This relatively simple editing method can be used to study the function of any gene of interest and allows for the generation of homozygous-edited C. elegans by CRISPR/Cas9 editing in less than two weeks.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Colágeno/genética , Testes Genéticos , Ribonucleoproteínas/metabolismo , Animais , Sequência de Bases , Primers do DNA/metabolismo , Gônadas/metabolismo , Homozigoto , Microinjeções , Edição de RNA/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Mapeamento por Restrição , Ribonucleoproteínas/genética , Streptococcus pyogenes/genética
12.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370943

RESUMO

A previously independent 56-year-old immunocompetent woman presented with septic shock in the setting of periorbital swelling and diffuse infiltrates on chest imaging. Blood cultures were positive for growth of group A Streptococcus (GAS). Broad spectrum antimicrobials were initiated with the inclusion of the antitoxin agent clindamycin. Necrosis of periorbital tissue was noted and surgical consultation was obtained. Débridement of both eyelids with skin grafting was performed. GAS was isolated from wound cultures and also observed on periorbital tissue microscopy. The final diagnosis was bilateral periorbital necrotising fasciitis (PONF) associated with invasive GAS infection. The patient had a prolonged intensive care unit course with input from multiple specialist teams. This case demonstrates the importance of early recognition and treatment of PONF, the profound systemic morbidity caused by these infections, and illustrates successful multidisciplinary teamwork.


Assuntos
Fasciite Necrosante/complicações , Choque Séptico/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus pyogenes/isolamento & purificação , Antibacterianos/uso terapêutico , Desbridamento , Quimioterapia Combinada , Pálpebras/microbiologia , Pálpebras/cirurgia , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/microbiologia , Fasciite Necrosante/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Choque Séptico/diagnóstico , Choque Séptico/terapia , Transplante de Pele , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/terapia , Resultado do Tratamento
13.
BMC Infect Dis ; 20(1): 817, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167878

RESUMO

BACKGROUND: Gastrointestinal (GI) mucormycosis is a rare and often deadly form of mucormycosis. Delayed diagnosis can lead to an increased risk of death. Here, we report a case of GI mucormycosis following streptococcal toxic shock syndrome in a virologically suppressed HIV-infected patient. CASE PRESENTATION: A 25-year-old Thai woman with a well-controlled HIV infection and Grave's disease was admitted to a private hospital with a high-grade fever, vomiting, abdominal pain, and multiple episodes of mucous diarrhea for 3 days. On day 3 of that admission, the patient developed multiorgan failure and multiple hemorrhagic blebs were observed on all extremities. A diagnosis of streptococcal toxic shock was made before referral to Siriraj Hospital - Thailand's largest national tertiary referral center. On day 10 of her admission at our center, she developed feeding intolerance and bloody diarrhea due to bowel ischemia and perforation. Bowel resection was performed, and histopathologic analysis of the resected bowel revealed acute suppurative transmural necrosis and vascular invasion with numerous broad irregular branching non-septate hyphae, both of which are consistent with GI mucormycosis. Peritoneal fluid fungal culture grew a grayish cottony colony of large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. A complete ITS1-5.8S-ITS2 region DNA sequence analysis revealed 100% homology with Rhizopus microsporus strains in GenBank (GenBank accession numbers KU729104 and AY803934). As a result, she was treated with liposomal amphotericin B. However and in spite of receiving appropriate treatment, our patient developed recurrent massive upper GI bleeding from Dieulafoy's lesion and succumbed to her disease on day 33 of her admission. CONCLUSION: Diagnosis of gastrointestinal mucormycosis can be delayed due to a lack of well-established predisposing factors and non-specific presenting symptoms. Further studies in risk factors for abdominal mucormycosis are needed.


Assuntos
Trato Gastrointestinal/microbiologia , Doença de Graves/complicações , Infecções por HIV/complicações , Mucormicose/complicações , Rhizopus/genética , Choque Séptico/complicações , Infecções Estreptocócicas/complicações , Streptococcus pyogenes/isolamento & purificação , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , DNA Fúngico/genética , Evolução Fatal , Feminino , Infecções por HIV/virologia , Humanos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Choque Séptico/diagnóstico , Choque Séptico/microbiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Síndrome , Tailândia
14.
Vestn Otorinolaringol ; 85(5): 57-60, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33140935

RESUMO

Acute respiratory infections (ORI) consistently occupy one of the leading places among infectious and inflammatory diseases in children. Most often, antibacterial drugs are used to stop the inflammatory process in the pharynx. Cationic peptides have an extremely broad antimicrobial spectrum, rendering the effect not only in bacterial infections and mycoses, and protozoans. THE PURPOSE OF THE STUDY: To demonstrate that the test drug is effective and safe for the treatment of acute viral pharyngitis in childhood. MATERIALS AND METHODS: In the period from September 2019 to January 2020, 120 patients aged 6 to 18 years were treated with the drug «Doritricin¼ for viral pharyngitis. RESULTS: According to the research results it can be concluded that «Diretrizes¼ provides fast and high effect in pediatric practice.


Assuntos
Faringite , Infecções Respiratórias , Infecções Estreptocócicas , Adolescente , Antibacterianos/uso terapêutico , Criança , Humanos , Peptídeos , Faringite/tratamento farmacológico , Faringe , Infecções Respiratórias/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes
15.
Vestn Otorinolaringol ; 85(5): 65-70, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33140937

RESUMO

The purpose of the study. To establish the effectiveness of symptom reduction and preventive action of the herbal drug Tonsilgon N (HD) as monotherapy for exacerbations of chronic tonsillitis/pharyngitis in adult patients. MATERIAL AND METHODS: The study included 60 adult male and female patients aged 18 to 60 years with an established diagnosis of acute tonsillopharyngitis. In total, each patient underwent 5 visits. Visit 1 - enrollment in the study and beginning of HD monotherapy, Visit 2 - on Day 7, Visit 3 - on Day 14 and completion of HD monotherapy, Visit 4 - on Day 60 and Visit 5 - on Day 180. The diagnosis of the disease and the examination of the patient was carried out on the basis of anamnesis, general clinical and ENT examination, palpation of regional lymph nodes. The severity of the clinical signs was evaluated on the basis of the symptom score. The general condition of the patient was also evaluated using a visual analogue scale (VAS) and the number of exacerbations of tonsillopharyngitis during the observation period. RESULTS: The number of exacerbations of chronic tonsillitis and episodes of ATP for 6 months after the end of treatment decreased 4.8 times compared to the previous period. During the course of treatment (14 days), complaints of patients with ATP (general health and/or fatigue, pain when swallowing, headache, cough, burning sensation, a lump in the throat, hoarseness, pain and dryness in the throat, difficulty swallowing) had a pronounced tendency to regression. Improvement was also noted on examination and clinical evaluation. According to the results of the analysis of the evaluation of general condition according to the VAS (according to the standard technique in cm), there was a significant improvement both during the treatment period by 2.2 times, and during the observation period (180 days) from the period of Visit 2 to Visit 4 by 31.3 times. CONCLUSION: The use of HD as monotherapy for non-streptococcal ATP has shown its high efficiency. The possibility of using Tonsilgon N was shown as a prophylactic agent that reduces the number of exacerbations of inflammatory diseases in the pharynx during the period after the treatment course.


Assuntos
Faringite , Infecções Estreptocócicas , Tonsilite , Adolescente , Adulto , Feminino , Medicina Herbária , Humanos , Masculino , Pessoa de Meia-Idade , Faringite/diagnóstico , Faringite/tratamento farmacológico , Streptococcus pyogenes , Tonsilite/diagnóstico , Tonsilite/tratamento farmacológico , Adulto Jovem
16.
Nat Commun ; 11(1): 5547, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144564

RESUMO

Methyl-NMR enables atomic-resolution studies of structure and dynamics of large proteins in solution. However, resonance assignment remains challenging. The problem is to combine existing structural informational with sparse distance restraints and search for the most compatible assignment among the permutations. Prior classification of peaks as either from isoleucine, leucine, or valine reduces the search space by many orders of magnitude. However, this is hindered by overlapped leucine and valine frequencies. In contrast, the nearest-neighbor nuclei, coupled to the methyl carbons, resonate in distinct frequency bands. Here, we develop a framework to imprint additional information about passively coupled resonances onto the observed peaks. This depends on simultaneously orchestrating closely spaced bands of resonances along different magnetization trajectories, using principles from control theory. For methyl-NMR, the method is implemented as a modification to the standard fingerprint spectrum (the 2D-HMQC). The amino acid type is immediately apparent in the fingerprint spectrum. There is no additional relaxation loss or an increase in experimental time. The method is validated on biologically relevant proteins. The idea of generating new spectral information using passive, adjacent resonances is applicable to other contexts in NMR spectroscopy.


Assuntos
Espectroscopia de Ressonância Magnética , Aminoácidos/química , Simulação por Computador , Humanos , Proteínas Ligantes de Maltose/química , Metilação , Reprodutibilidade dos Testes , Streptococcus pyogenes/metabolismo
17.
Epidemiol Mikrobiol Imunol ; 69(3): 128-133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33086854

RESUMO

Úvod: Biomarkery jsou u septických pacientů využívány jak k diagnostice sepse, tak k antibiotickému stewardshipu. Sepse vyvolaná gramnegativními bakteriemi mívá odlišné charakteristiky, především vysoký prokalcitonin vs C-reaktivní protein v porovnání se sepsí vyvolanou grampozitivními bakteriemi. Avšak jednotlivá infekční agens, především Streptococcus pyogenes, nemusí do tohoto schématu zapadat, což může vest k nesprávné iniciální volbě antibiotika. Metody: Retrospektivní analýza biomarkerů, iniciální volby antibiotické léčby a výsledků léčby u pacientů se sepsí vyvolanou S. pyogenes, Escherichia coli a Staphylococcus aureus. Hodnoty biomarkerů byly porovnány pomocí Kruskal-Wallis testu s následným Dunn post-Hoc testem s prahem p < 0,05. Výsledky: Hodnoty prokalcitoninu byly nejvyšší u sepse vyvolané S. pyogenes (12,51 ng/ml, IQR: 6,26-48,38 ng/ml) oproti sepsi vyvolaná E. coli (4,30 ng/ml, IQR: 1,50-10,00 ng/ml, p < 0,001) a S. aureus (0,75 ng/ml, QR: 0,34-1,62 ng/ml, p < 0,001). Poměr neutrofilů a lymfocytů vykazoval stejné charakteristiky jako prokalcitonin. Správná iniciální antibiotická léčba byla v souboru S. pyogenes 11,29 % v porovnání s 99,3 % a 100 % u S. aureus a E. coli skupin. Závěr: Oproti předchozím studiím byly v našem souboru pozorovány nejvyšší hodnoty prokalcitoninu u pacientů se sepsí vyvolanou S. pyogenes spíše než gramnegativními bakteriemi. Vysoké hodnoty prokalcitoninu imitující gramnegativní zánětlivou odpověď přispěli k ovlivnění výběru iniciální antibiotické léčby (bez znalosti původce), což mohlo vést k vyšší mortalitě u této skupiny pacientů. Proto doporučujeme přehodnocení významu prokalcitoninu v diagnostice sepse pro zlepšení přežití i kvality života pacientů.


Assuntos
Antibacterianos/uso terapêutico , Sepse/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Biomarcadores , Escherichia coli , Staphylococcus aureus
18.
Nat Commun ; 11(1): 5018, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024089

RESUMO

The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins.


Assuntos
Exotoxinas/metabolismo , Prófagos/genética , Streptococcus pyogenes/patogenicidade , Streptococcus pyogenes/virologia , Animais , Proteínas de Bactérias/farmacologia , Linhagem Celular , Eritrócitos/efeitos dos fármacos , Exotoxinas/genética , Feminino , Glutationa/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Faringe/citologia , Escarlatina/epidemiologia , Escarlatina/microbiologia , Streptococcus pyogenes/genética , Estreptolisinas/farmacologia , Superantígenos/genética , Superantígenos/metabolismo
19.
Medicina (B Aires) ; 80(5): 531-540, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-33048799

RESUMO

Severe skin and soft tissue infections present a high morbidity and mortality and require a complex surgical treatment. Its estimated annual incidence is 0.3 to 5 cases per 10 000 people. The most common etiologic agents are Streptococcus pyogenes, Staphylococcus aureus, anaerobes and gram-negative bacilli. A prompt diagnosis and the timely initiation of an empirical antibiotic scheme and repeated surgical debridement can avert a worrisome outcome. New therapeutic options are promising, especially for infections caused by multidrug resistant germs. A multidisciplinary approach is fundamental for the correct management of these conditions.


Assuntos
Infecções dos Tecidos Moles/diagnóstico , Antibacterianos/uso terapêutico , Humanos , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/terapia , Infecções dos Tecidos Moles/terapia , Infecções Estafilocócicas/tratamento farmacológico , Streptococcus pyogenes
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