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Bacillus anthracis causes anthrax disease and can affect humans and other animals. This zoonotic disease has an impact on the economic and health aspects. B. anthracis population is divided into three major clades: A (with worldwide distribution), B, and C (restricted to specific regions). Anthrax is most common in agricultural regions of central and southwestern Asia, sub-Saharan Africa, Southern and Eastern Europe, the Caribbean, and Central and South America. Here, we sequenced by short and long reads technologies to generate a hybrid assembly of a lineage of B. anthracis recovered from animal source in the 1960s in Brazil. Isolate identification was confirmed by phenotypic/biochemical tests and MALDI-TOF MS. Antimicrobial susceptibility was performed by in-house broth microdilution. B. anthracis IAL52 was susceptible to penicillin, amoxicillin, doxycycline, levofloxacin, and tetracycline but non-susceptible to ciprofloxacin. IAL52 was classified as sequence type ST2, clade A.Br.069 (V770 group). Sequencing lineages of B. anthracis, especially from underrepresented regions, can help determine the evolution of this critical zoonotic and virulent pathogen.
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Antraz , Bacillus anthracis , Animais , Humanos , Bacillus anthracis/genética , Antraz/epidemiologia , Antraz/veterinária , Brasil/epidemiologia , Zoonoses , Sequenciamento Completo do Genoma/veterináriaRESUMO
Introducción. La epidemiología del ántrax en Perú es poco conocida. Su alto potencial epidémico y epizoótico podría amenazar la salud pública, especialmente desde sus regiones endémicas. Objetivo. Caracterizar los casos de ántrax humano en Perú del 2015 al 2019. Métodos. Se realizó un estudio transversal retrospectivo, a partir de los datos del Sistema Nacional de Vigilancia Epidemiológica e investigaciones de brotes en Perú del 2015 al 2019. Resultados. 71 casos de ántrax humano fueron registrados, 34 % (n = 24) confirmados y66 % (n = 47) probables. Los más afectados fueron varones (55 %) y el grupo etario de 30 a 59 años (45 %). Los casos estuvieron distribuidos principalmente en la costa norte del país. La forma cutánea autolimitada en miembros superiores fue la presentación clínica más frecuente. El 94 % (n = 67) de los casos tuvieron contacto con ganado vacuno infectado. Conclusión. Los casos de ántrax humano en Perú fueron en su mayoría de la forma cutánea, que se presentaron por brotes focalizados en áreas con antecedentes de trasmisión zoonótica. Este reporte pretende aportar al conocimiento epidemiológico de esta enfermedad y servir como insumo en la implementación de medidas de prevención y control.
Introduction. The epidemiology of anthrax in Peru is poorly understood. Its high epidemic and epizootic potential could threaten public health, especially in its endemic regions. Objective. To characterize cases of human anthrax in Peru from 2015 to 2019. Methods. A retrospective cross-sectional study was carried out; based on data from the National Epidemiological Surveillance System and investigations of anthrax outbreaks from 2015 to 2019 in Peru. Results. 71 cases of human anthrax were registered, 34 % (n = 24)confirmed and 66 % (n = 47) probable. The most affected were males (55 %) and the age group from 30to 59 years (45 %), distributed mainly on the north coast of the country. The self-limited cutaneous form was the most frequent clinical presentation. 94% (n = 67) of the cases had contact with infected cattle. Conclusions. The cases of human anthrax in Peru appear as focalized outbreaks in areas with a history of zoonotic transmission. This report aims to contribute to the epidemiological knowledge of this disease and serve as input in the implementation of prevention and control measures.
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It is still a challenge to develop needle-free mucosal vaccines. Despite progress in the development of the influenza vaccine, it must be reformulated annually because of antigenic changes in circulating influenza viral strains. Due to seasonal drift and shift of circulating strains, the influenza vaccine does not always match the circulating strains, and included adjuvants are not sufficient to induce a protective effect with long-lived memory cells. The adjuvants play a major role in the immune responses to a vaccine. Interestingly, the Bacillus anthracis detoxified anthrax edema toxin, which composes of protective antigen PA and N-fragment of edema factor (EFn), has shown improved effects for humoral and cellular immune responses. Here we describe the design of a universal influenza vaccine construct that consists of three tandem M2e repeats of the influenza antigen plus HA2 and detoxified toxin EFn, which is associated with the PA component, as well as the techniques used to corroborate protection. We present two major parts of description to demonstrate the vaccine strategy, using detoxified anthrax toxin for intranasal delivery of influenza antigen: (1) vaccine candidate design, production, and purification; (2) influenza virus microneutralization assay and cellular responses and lethal challenge with influenza viruses and B. anthracis Sterne spores. In the methods detailed here, we used different versions of the M2e-HA2 proteins.
Assuntos
Toxinas Bacterianas , Proteínas de Transporte , Vacinas/administração & dosagem , Adjuvantes Imunológicos , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/imunologia , Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Ensaio de Imunoadsorção Enzimática , Imunização , Vacinas contra Influenza/imunologia , Camundongos , Testes de Neutralização , Linfócitos T/imunologia , Linfócitos T/metabolismo , VacinaçãoRESUMO
Bacillus cereus sensu lato strains (B. cereus group) are widely distributed in nature and have received interest for decades due to their importance in insect pest management, food production and their positive and negative repercussions in human health. Consideration of practical uses such as virulence, physiology, morphology, or ill-defined features have been applied to describe and classify species of the group. However, current comparative studies have exposed inconsistencies between evolutionary relatedness and biological significance among genomospecies of the B. cereus group. Here, the combined analyses of core-based phylogeny and all versus all Average Nucleotide Identity values based on 2116 strains were conducted to update the genomospecies circumscriptions within B. cereus group. These analyses suggested the existence of 57 genomospecies, 37 of which are novel, thus indicating that the taxonomic identities of more than 39% of the analyzed strains should be revised or updated. In addition, we found that whole-genome in silico analyses were suitable to differentiate genomospecies such as B. anthracis, B. cereus and B. thuringiensis. The prevalence of toxin and virulence factors coding genes in each of the genomospecies of the B. cereus group was also examined, using phylogeny-aware methods at wide-genome scale. Remarkably, Cry and emetic toxins, commonly assumed to be associated with B. thuringiensis and emetic B. paranthracis, respectively, did not show a positive correlation with those genomospecies. On the other hand, anthrax-like toxin and capsule-biosynthesis coding genes were positively correlated with B. anthracis genomospecies, despite not being present in all strains, and with presumably non-pathogenic genomospecies. Hence, despite these features have been so far considered relevant for industrial or medical classification of related species of the B. cereus group, they were inappropriate for their circumscription. In this study, genomospecies of the group were accurately affiliated and representative strains defined, generating a rational framework that will allow comparative analysis in epidemiological or ecological studies. Based on this classification the role of specific markers such as Type VII secretion system, cytolysin, bacillolysin, and siderophores such as petrobactin were pointed out for further analysis.
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Bacillus anthracis , Bacillus , Bacillus cereus/genética , Humanos , Fenótipo , FilogeniaRESUMO
Canine and human osteosarcomas (OSA) share similarities. Novel therapies are necessary for these tumours. The Bacillus anthracis toxin was reengineered to target and kill cells with high expressions of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA). Since canine OSA express MMPs and uPA, we assessed whether the reengineered toxin could show efficacy against these tumours. Two OSA cell lines (canine D17 and human MG63) and a non-neoplastic canine osteoblastic cell line (COBS) were used. Cells were treated with different concentrations of the reengineered anthrax toxin and cell viability was quantified using MTT assay. The cell cycle, apoptosis, and necrosis were analysed by flow cytometry. The wound-healing assay was performed to quantify the migration capacity of treated cells. D17 and MG63 cells had significantly decreased viability after 24 h of treatment. Cell cycle analysis revealed that OSA cells underwent apoptosis when treated with the toxin, whereas COBS cells arrested in the G1 phase. The wound-healing assay showed that D17 and MG63 cells had a significantly reduced migration capacity after treatment. These results point for the first time towards the in vitro inhibitory effects of the reengineered anthrax toxin on OSA cells; this reengineered toxin could be further tested as a new therapy for OSA.
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Antígenos de Bactérias/farmacologia , Antineoplásicos/farmacologia , Toxinas Bacterianas/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Animais , Antígenos de Bactérias/genética , Apoptose/efeitos dos fármacos , Toxinas Bacterianas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Masculino , Metaloproteinases da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Invasividade Neoplásica , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Engenharia de ProteínasRESUMO
Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.
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Antígenos de Bactérias/uso terapêutico , Antineoplásicos/uso terapêutico , Toxinas Bacterianas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Melanoma/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/farmacologia , Antineoplásicos/farmacologia , Toxinas Bacterianas/genética , Toxinas Bacterianas/farmacologia , Doenças do Cão/metabolismo , Doenças do Cão/patologia , Cães , Feminino , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Melanoma/veterinária , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/veterinária , Engenharia de Proteínas , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
ABSTRACT China's compulsory annual livestock anthrax vaccination policy has remarkably reduced but not completely eradicated human anthrax infections. Herein we describe a sporadic human cutaneous anthrax outbreak involving two cases in 2018 in Shaanxi Province, both involving herdsman who dealt with unvaccinated and potentially sick cattle. Both patients showed Bacillus anthracis-positive blister smear and blood culture. Treatment with penicillin was followed by uneventful recovery for both. The prompt performance of the prophylactic measures successfully interrupted the further transmission of this sporadic human cutaneous anthrax outbreak.
Assuntos
Humanos , Masculino , Adulto , Dermatopatias Bacterianas/patologia , Antraz/patologia , Penicilinas/uso terapêutico , Bacillus anthracis/isolamento & purificação , China/epidemiologia , Surtos de Doenças , Resultado do Tratamento , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/epidemiologia , Antraz/tratamento farmacológico , Antraz/epidemiologia , Antibacterianos/uso terapêuticoRESUMO
China's compulsory annual livestock anthrax vaccination policy has remarkably reduced but not completely eradicated human anthrax infections. Herein we describe a sporadic human cutaneous anthrax outbreak involving two cases in 2018 in Shaanxi Province, both involving herdsman who dealt with unvaccinated and potentially sick cattle. Both patients showed Bacillus anthracis-positive blister smear and blood culture. Treatment with penicillin was followed by uneventful recovery for both. The prompt performance of the prophylactic measures successfully interrupted the further transmission of this sporadic human cutaneous anthrax outbreak.
Assuntos
Antraz/patologia , Dermatopatias Bacterianas/patologia , Adulto , Antraz/tratamento farmacológico , Antraz/epidemiologia , Antibacterianos/uso terapêutico , Bacillus anthracis/isolamento & purificação , China/epidemiologia , Surtos de Doenças , Humanos , Masculino , Penicilinas/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND Bacillus anthracis is the aetiologic agent of anthrax, a re-emerging, septicaemic, haemorrhagic and lethal disease that affects humans, domestic ruminants and wildlife. Plasmids pXO1 and pXO2 are attributes that confer pathogenicity to B. anthracis strains. This bacterium was used as biological weapon in the World Wars and in the biological attack in the United States of America at 2001. B. anthracis is classified as a Tier 1 bioterrorism agent by the Centers for Diseases Control and Prevention. Anthrax is recognised as a re-emerging disease. Several studies concerning the dynamics of B. anthracis cycle in soil revealed that nonpathogenic B. anthracis strains due to lack of pXO2 plasmid are commonly found in some types of soil. OBJECTIVES This study aimed isolation and identification of B. anthracis spores in soil samples of the state of Rio de Janeiro, Brazil. METHODS Phenotypic and genotypic approaches were used to identify isolates including MALDI-TOF/MS, motility test, susceptibility to gamma phage and penicillin, survey for pag and cap genes as surrogates of pXO1 and pXO2 plasmids, respectively, and sequencing of 16SrRNA-encoding gene. Physicochemical analysis of the soil samples were carried out to describe soil characteristics. FINDINGS We observed the presence of one B. anthracis pXO1+ and pXO2- isolated from clay loam soil; one B. anthracis-like strain pXO1+ and pXO2-isolated from loamy sand; and 10 Bacillus spp. strains sensitive to phage-gamma that need better characterisation to define which their species were recovered from loamy sand. MAIN CONCLUSIONS This work showed promising results and it was the first study to report results from an active surveillance for B. anthracis in Brazil.
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Humanos , Plasmídeos/análise , Microbiologia do Solo , Esporos Bacterianos , Bacillus anthracis/isolamento & purificação , DNA Bacteriano/genética , Reação em Cadeia da Polimerase/métodos , Fatores de Virulência/genética , Plasmídeos/genética , Solo , Bacillus anthracis/genética , Bacillus anthracis/patogenicidade , Toxinas Bacterianas , Virulência , Brasil , DNA Bacteriano/análise , Análise de Sequência de DNA , Antígenos de BactériasRESUMO
Abstract Ecthyma gangrenosum is an uncommon dermatological manifestation characterized by round, indurated ulcers with a central necrotic black eschar and surrounding erythema. This report describes the case of a 5-year-old girl, affected by acute lymphocytic leukemia, presenting with a black eschar on her right thigh. Such lesions should always be correctly identified to avoid potentially fatal bacteraemia. Furthermore, because of its similar clinical presentation, cutaneous anthrax must be ruled out.
Assuntos
Humanos , Feminino , Pré-Escolar , Infecções por Pseudomonas/microbiologia , Úlcera Cutânea/microbiologia , Ectima/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Pseudomonas aeruginosa , Infecções por Pseudomonas/patologia , Úlcera Cutânea/patologia , Ectima/patologiaRESUMO
Bacillus anthracis protective antigen (PA) is a well known and relevant immunogenic protein that is the basis for both anthrax vaccines and diagnostic methods. Properly folded antigenic PA is necessary for these applications. In this study a high level of PA was obtained in recombinant Escherichia coli. The protein was initially accumulated in inclusion bodies, which facilitated its efficient purification by simple washing steps; however, it could not be recognized by specific antibodies. Refolding conditions were subsequently analyzed in a high-throughput manner that enabled nearly a hundred different conditions to be tested simultaneously. The recovery of the ability of PA to be recognized by antibodies was screened by dot blot using a coefficient that provided a measure of properly refolded protein levels with a high degree of discrimination. The best refolding conditions resulted in a tenfold increase in the intensity of the dot blot compared to the control. The only refolding additive that consistently yielded good results was L-arginine. The statistical analysis identified both cooperative and negative interactions between the different refolding additives. The high-throughput approach described in this study that enabled overproduction, purification and refolding of PA in a simple and straightforward manner, can be potentially useful for the rapid screening of adequate refolding conditions for other overexpressed antigenic proteins.
El antígeno protector de Bacillus anthracis (protective antigen, PA) es una importante proteína inmunogénica, en la que se basan tanto las vacunas contra el ántrax/carbunclo como varios métodos diagnósticos. Para estas aplicaciones es esencial que el PA mantenga sus propiedades antigénicas, para lo cual debe estar correctamente plegado. En este estudio se obtuvieron altos niveles del PA en Escherichia coli recombinante. Inicialmente, la proteína se acumuló desnaturalizada en cuerpos de inclusión, lo que facilitó su eficiente purificación en simples pasos de lavado, pero no fue reconocida por anticuerpos específicos. Se analizaron las condiciones de replegado con un sistema de alto rendimiento, evaluando simultáneamente casi un centenar de condiciones diferentes. La recuperación de la capacidad del PA de ser reconocido por los anticuerpos se evaluó por dot blot utilizando un coeficiente que proporcionó una medida de los niveles de proteína correctamente plegada, con un alto grado de discriminación. Las mejores condiciones de renaturalización permitieron un aumento de diez veces en la intensidad de los dot blots con respecto del control. El único aditivo que produjo buenos resultados de forma constante fue la L-arginina. El análisis estadístico de las interacciones entre los diferentes aditivos de replegado permitió identificar tanto interacciones cooperativas como negativas. El enfoque de alto rendimiento descripto en este trabajo, que permitió la sobreproducción, purificación y plegado del PA de una manera sencilla y directa, puede ser potencialmente útil para el rápido screening de las condiciones adecuadas de replegado cuando se sobreexpresan otras proteínas antigénicas.
Assuntos
Redobramento de Proteína/efeitos dos fármacos , Anticorpos/análise , Antígenos/análise , Bacillus anthracis/efeitos dos fármacos , Bacillus anthracis/imunologia , Dobramento de Proteína/efeitos dos fármacosRESUMO
Bacillus anthracis protective antigen (PA) is a well known and relevant immunogenic protein that is the basis for both anthrax vaccines and diagnostic methods. Properly folded antigenic PA is necessary for these applications. In this study a high level of PA was obtained in recombinant Escherichia coli. The protein was initially accumulated in inclusion bodies, which facilitated its efficient purification by simple washing steps; however, it could not be recognized by specific antibodies. Refolding conditions were subsequently analyzed in a high-throughput manner that enabled nearly a hundred different conditions to be tested simultaneously. The recovery of the ability of PA to be recognized by antibodies was screened by dot blot using a coefficient that provided a measure of properly refolded protein levels with a high degree of discrimination. The best refolding conditions resulted in a tenfold increase in the intensity of the dot blot compared to the control. The only refolding additive that consistently yielded good results was L-arginine. The statistical analysis identified both cooperative and negative interactions between the different refolding additives. The high-throughput approach described in this study that enabled overproduction, purification and refolding of PA in a simple and straightforward manner, can be potentially useful for the rapid screening of adequate refolding conditions for other overexpressed antigenic proteins.
Assuntos
Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/imunologia , Bacillus anthracis/imunologia , Bacillus anthracis/metabolismo , Modelos Moleculares , Redobramento de ProteínaRESUMO
Anthrax, caused by Bacillus anthracis (B anthracis), poses a potential threat as a bioterror agent because after inhalation, the spores rapidly cause bacteraemia and toxaemia. It produces a toxin consisting of three proteins ie protective antigen (PA), oedema factor (EF) and lethal factor (LF). Protective antigen plays a central role in the pathophysiology of anthrax and offers an excellent therapeutic target for treatment of anthrax. Raxibacumab is a recombinant, fully human, IgG1λ monoclonal antibody directed against PA of B anthracis. It inhibits PA binding to the anthrax toxin receptor and inhibits toxin-mediated cell death. It has been approved under animal rule or animal efficacy rule by the United States Food and Drug Administration which comes into play when it is not feasible or ethical to perform controlled clinical trials in humans. It has shown promising results in various animal studies which includes significantly improved survival rates in the raxibacumab group than non-raxibacumab group.
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Após 2001, a utilização de patógenos reforçou seu emprego como arma de guerra. Este estudo descritivo tem por objetivo discutir estratégias de contingenciamento em ataque por anthrax, auxiliando no reconhecimento precoce e estabelecimento de medidas de contenção. Profissionais de saúde necessitam reconhecer a infecção, pois em atentados, o elemento-chave é médico e não militar. O anthrax por inalação é a forma de atentado mais provável com 100% de mortalidade, caso não haja tratamento imediato. É altamente resistente; tem período de incubação de um a seis dias; seus sintomas iniciais são similares à influenza; só permite diagnóstico em NB3; a vacina é aquela recomendada para ocupações de risco, de disponibilidade restrita; e requer profilaxia antibiótica longa.
As from 2001, the use of biological agents reinforced the possibility of its consolidation as warfare. This descriptive study aims to discuss the contingency strategies for anthrax attack, seeking early recognition and establishment of containment measures. Health professionals need to recognize the infection since the key-element during an attack is medical rather than military one. Anthrax inhalation is the most likely form of attack with 100% mortality rate, if no immediate treatment is provided. The virus is highly resistant; has an incubation period of one to six days; its early symptoms are similar to influenza's; diagnosis is only allowed in NB3; the vaccine is the one recommended for risk occupations, of restricted availability; and requires long antibiotic prophylaxis.
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In this study we evaluate the capacity of Virtual Hybridization to identify between highly related bacterial strains. Eight genomic fingerprints were obtained by virtual hybridization for the Bacillus anthracis genome set, and a set of 15,264 13-nucleotide short probes designed to produce genomic fingerprints unique for each organism. The data obtained from each genomic fingerprint were used to obtain hybridization patterns simulating a DNA microarray. Two virtual hybridization methods were used: the Direct and the Extended method to identify the number of potential hybridization sites and thus determine the minimum sensitivity value to discriminate between genomes with 99.9% similarity. Genomic fingerprints were compared using both methods and phylogenomic trees were constructed to verify that the minimum detection value is 0.000017. Results obtained from the genomic fingerprints suggest that the distribution in the trees is correct, as compared to other taxonomic methods. Specific virtual hybridization sites for each of the genomes studied were also identified.
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In the present work, we applied docking and molecular dynamics techniques to study 11 compounds inside the enzymes dihydrofolate reductase (DHFR) from the biological warfare agent Bacillus anthracis (BaDHFR) and Homo sapiens sapiens (HssDHFR). Six of these compounds were selected for a study with the mutant BaF96IDHFR. Our results corroborated with experimental data and allowed the proposition of a new molecule with potential activity and better selectivity for BaDHFR.
Assuntos
Antibacterianos/química , Bacillus anthracis/química , Proteínas de Bactérias/química , Antagonistas do Ácido Fólico/química , Bibliotecas de Moléculas Pequenas/química , Tetra-Hidrofolato Desidrogenase/química , Bacillus anthracis/enzimologia , Bacillus anthracis/genética , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Armas Biológicas , Domínio Catalítico , Desenho de Fármacos , Humanos , Cinética , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação , Especificidade da Espécie , Relação Estrutura-Atividade , Tetra-Hidrofolato Desidrogenase/genética , TermodinâmicaRESUMO
Bacillus anthracis es un bacilo gram positivo del grupo Bacillus cereus, que posee un genoma extremadamente monomórfco y comparte gran similitud fsiológica y de estructura genética con B. cereus y Bacillus thuringiensis. En este artículo se describen nuevos métodos moleculares para la identifcación y tipifcación de B. anthracis, basados en repeticiones en tándem de número variable o en diferencias genéticas detectadas por secuenciación, desarrollados en los últimos años. Los aspectos moleculares de los factores de virulencia tradicionales, cápsula, antígeno protector, factor letal y factor edema se describen en profundidad, junto con factores de virulencia recientemente propuestos, como los sideróforos, petrobactina y bacilibactina, la adhesina de la capa S y la lipoproteína MntA. También se detalla la organización molecular de los megaplásmidos pXO1 y pXO2, incluyendo la isla de patogenicidad de pXO1. El esqueleto genético de estos plásmidos se ha encontrado en otras especies relacionadas, probablemente debido a eventos de transferencia lateral. Finalmente, se presentan los dos receptores celulares del antígeno protector, ANTXR1/TEM8 y ANTXR2/CMG2, esenciales en la interacción del patógeno con el hospedador. Los estudios moleculares realizados en los últimos años han permitido aumentar enormemente el conocimiento de los diferentes aspectos de este microorganismo y su relación con el hospedador, pero a la vez han abierto nuevos interrogantes sobre este notorio patógeno.
Bacillus anthracis, a gram-positive rod belonging to the Bacillus cereus group, has an extremely monomorphic genome, and presents high structural and physiological similarity with B. cereus and Bacillus thuringiensis. In this work, the new molecular methods for the identifcation and typing of B. anthracis developed in the last years, based on variable number tandem repeats or on genetic differences detected through sequencing, are described. The molecular aspects of traditional virulence factors: capsule, protective antigen, lethal factor and edema factor are described in depth, together with virulence factors recently proposed, such as the siderophores petrobactin and bacillibactin, the S-layer adhesin and the MntA lipoprotein. It is detailed the molecular organization of megaplasmids pXO1 and pXO2, including the pathogenicity island of pXO1. The genetic skeleton of these plasmids has been observed in related species, and this could be attributed to lateral gene transfer. Finally, the two anthrax toxin protective antigen receptors, ANTXR1/TEM8 and ANTXR2/CMG2, essential for the interaction of the pathogen with the host, are presented. The molecular studies performed in recent years have greatly increased knowledge in different aspects of this microorganism and its relationship with the host, but at the same time they have raised new questions about this noted pathogen.
Assuntos
Animais , Humanos , Antraz/microbiologia , Bacillus anthracis/fisiologia , Antraz/epidemiologia , Antraz/veterinária , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/fisiologia , Toxinas Bacterianas , Técnicas de Tipagem Bacteriana , Sequência de Bases , Bacillus anthracis/classificação , Bacillus anthracis/genética , Bacillus anthracis/patogenicidade , Bacillus/classificação , Cápsulas Bacterianas/fisiologia , DNA Bacteriano/genética , Ilhas Genômicas/fisiologia , Repetições Minissatélites , Dados de Sequência Molecular , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiologia , Plasmídeos , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/fisiologia , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Virulência/genética , Virulência/fisiologia , ZoonosesRESUMO
Introducción: ántrax o carbunco, es una enfermedad infecciosa causada por bacterias llamadas bacillus anthracis. La infección en los humanos compromete con mayor frecuencia la piel, el tracto gastrointestinal o los pulmones. La infección en humanos ocurre por contacto directo con carne, restos o productos de animales contaminados como: cuero, pelo, lana o huesos, es un contacto generalmente ocupacional. Caso clínico: paciente masculino, de 64 años de edad, raza negra y de profesión obrero agrícola. Durante un periodo de 8 días, previos a su ingreso, presentó fiebre, sin precisar gradación, con escalofríos, decaimiento, cefalea universal pulsátil y pérdida del apetito; notó además aumento local del volumen en la región peri orbitaria derecha con secreción purulenta, acompañándose de adenopatías submaxilares dolorosas y movibles. Con estos elementos se decidió su hospitalización. Al segundo día de estar en sala apareció una lesión costrosa de alrededor de cuatro centímetros de diámetro con un color negruzco, de bordes bien definidos, con halo eritematoso que le impedía la abertura palpebral. Se concluyó que este paciente estuvo en contacto con carnes de ganado vacuno. Conclusiones: se diagnóstico al paciente ántrax cutáneo, se tuvo en cuenta los elementos clínicos epidemiológicos y de laboratorio. Al duodécimo día de tratamiento con penicilina cristalina, se desprendió de forma espontánea la costra, sin dejar secuelas. En este caso no se presentó ninguna complicación clínica. El paciente es egresado con diagnóstico confirmado por el laboratorio, de infección por el bacillus anthracis.
Introduction: anthrax or carbuncle is an infectious disease caused by Bacillus anthracis bacteria. In humans the infection most frequently affects the skin, the gastrointestinal tract or the lungs; it direct contact with parts of infected animals or by consuming their meat, in a occupational contact generally. Clinical case: a 64 years old, masculine, black race patient, agricultural worker as profession. During a period of 8 days, previous to his admission, presented fever, without specifying gradation, with shivers, declining, and pulsatile universal headache and lost of appetite; the patient also noticed local increase of the volume in the right periorbital region with purulent secretion, accompanying by painful and movable submaxilla. With these elements was decided his hospitalization. To the second day of being admitted a crustosus lesion appeared around four centimeters of diameter with a blackish color, of well-defined rims, with erythematous halo impeded him the palpebral opening. It was concluded this patient was in contact with meats of cattle. Conclusions: it was diagnosed him cutaneous anthrax; it was taking into account the epidemiologic, clinical and laboratory elements. To the twelfth day of treatment with crystalline penicillin, the crust came off in a spontaneous way, without any sequelae. In this case any clinical complication was not presented. The patient was discharged with a diagnostic confirmed by the laboratory, of infection by bacillus anthracis.