ABSTRACT
La tuberculosis pulmonar (TB) es un problema de salud pública a nivel mundial. La Organización Mundial de la Salud estimó para el año 2017 alrededor de 10 millones de personas enfermas y 1,3 millones de muertes. La facultad que posee MTB para modular la respuesta inmune, sobrevivir y persistir bajo el ambiente hostil en el hospedero y en la TB latente ha sido ampliamente investigada, y requiere de regulación y control de la expresión genética. El objetivo es presentar una revisión de las investigaciones relacionadas con los reguladores de la expresión de genes de MTB que están asociados con la virulencia, persistencia y supervivencia en la TB latente. Se hizo una revisión de las investigaciones de los últimos 20 años. Se concluye que MTB posee una maquinaria genética que controla la expresión de genes que participan en virulencia y persistencia, en respuesta a la hipoxia, estrés oxidativo, falta de nutrientes y pH ácido. Entre ellos, participan los sistemas de dos componentes, factores sigma y reguladores transcripcionales. En algunos casos se ha comprobado que funcionan interconectados como una red. Los hallazgos de las investigaciones aportan conocimientos para el descubrimiento de nuevos blancos para el desarrollo de drogas antituberculosas, nuevas vacunas y métodos de diagnóstico de la TB, con el propósito de proveer nuevas estrategias para el control de la enfermedad(AU)
Pulmonary tuberculosis (TB) is a public health problem worldwide. The World Health Organization estimated about 10 million sick people and 1.3 million deaths in 2017. The ability of MTB to modulate the immune response, survive and persist under the hostile environment in the host and in latent TB has been extensively investigated, and requires regulation and control of genetic expression. The objective is to present a review of research related to regulators of MTB gene expression that are associated with virulence, persistence and survival in latent TB. A review of the investigations of the last 20 years was made. Finally, it is concluded that MTB has a genetic machinery that controls the expression of genes that participate in virulence and persistence in response to hypoxia, oxidative stress, lack of nutrients and acidic pH. Among them, two-component systems, sigma factors and transcriptional regulators participate. It has been proven that they work interconnected as a network in some cases. The research findings provide insights for the discovery of new targets for the development of anti-tuberculosis drugs, new vaccines and methods for diagnosis of TB, with the purpose of providing new strategies for disease control(AU)
Subject(s)
Humans , Male , Female , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/prevention & control , Tuberculosis, Pulmonary/epidemiology , Virulence FactorsABSTRACT
We designed a strategy for the sequencing and bioinformatical characterization of the 1,3-propanediol operon regulator genes from the Colombian Clostridium sp. strain IBUN13A, which is taxonomically related to Clostridium butyricum. Three genes are proposed to be involved in the operon's transcriptional activity, the dhaS and dhaA genes through a two-component system and the third gene named dhaY, which encodes a putative transcriptional regulator similar to the domains of the dhaS/A system. Phylogenetic analyses indicated that the predicted proteins had a modular structure consisting of domains homologous to different signal transduction systems, but had significant differences concerning their conserved residues, pointing to the possibility that they constitute ancestral domains. In accordance with the prediction of functions, we propose a mechanism of regulation of the proteins studied of the 1,3-propanediol operon of the native strain, as a response to the presence of glycerol in the medium, which provides valuable information on the overall regulation of the glycerol metabolism in Clostridium sp.
Se diseñó una estrategia de amplificación, secuenciación y caracterización bioinformática de los genes reguladores del operón 1,3-propanediol (1,3-PD) de la cepa nativa colombiana Clostridium sp. IBUN 13A, relacionada taxonómicamente con Clostridium butyricum. Se identificaron tres genes que pueden estar involucrados en la regulación transcripcional de dicho operón: los genes dhaS y dhaA -a través de un sistema de transducción de señales de dos componentes-y un tercer gen que se denominó dhaY, que codifica para un regulador transcripcional putativo, similar a los dominios presentes en las proteínas del sistema DhaS/A. Los análisis filogenéticos indican que las proteínas predichas presentan una estructura modular con dominios homólogos a diferentes sistemas de transducción de señales, pero muestran diferencias importantes en los residuos conservados, lo que sugiere que podrían ser estos los dominios ancestrales. La predicción de funciones postula un mecanismo de regulación de las proteínas estudiadas sobre el promotor del operón 1,3-PD de la cepa nativa como respuesta a la presencia de glicerol en el medio, lo cual aporta información importante sobre la regulación global del metabolismo del glicerol en Clostridium sp.
Nesta pesquisa foi feita uma estratégia para a amplificacäo, sequenciamento e caracterizacäo bioinformática dos genes reguladores do operon 1,3 propanodiol (1,3-PD) da cepa colombiana Clostridium sp. IBUN 13A, relacionada taxonomicamente com o Clostridium butyricum. Tèm sido identificados tres genes que podem estar envolvidos na regulacáo transcricional do operon. Os genes dhaS e dhaA por meio de um sistema de dois componentes e o terceiro gene nomeado de dhaY, que codifica para um regulador transcridonal putativo, parecido com os dominios presentes nas proteínas do sistema DhaS/A. A análise filogenètica mostra que estas proteínas apresentam uma estrutura modular com dominios homólogos a diferentes sistemas de traducáo de sinais, mas pressupöem diferencas importantes nos residuos conservados, indicando provavelmente que possam constituir os dominios ancestrais. De acordo com a predicáo de funcöes, é postulado um mecanismo de regulacáo do sistema DhaS/A, DhaY sobre o promotor do operon 1,3-DP da cepa nativa, como resposta à presenca de glicerol no meio, aportando informacöes importantes da regulacáo global do metabolismo do glicerol no Clostridium sp.
ABSTRACT
PURPOSE: Low-affinity penicillin-binding protein PBP 2a encoded by mecA is closely related to methicillin resistance in staphylococci, and the expression of PBP 2a is controlled by regulator elements encoded by mecR1 and mecI. Deletion or mutation which occurred in mecI is considered to be associated with constitutive production of PBP 2a. We investigated the distribution of mec regulator genes and the presence of the mutations in mecI among mecA gene-positive methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase negative Staphylococcus (MRCNS) strains. METHODS: A total of 28 MRSA and 26 MRCNS clinical strains were isolated at Chung-Ang University Hospital. The distribution of mec regulator genes and the presence of mutations in mecI were analyzed using polymerase chain reaction and direct sequencing. RESULTS: In 28 MRSA and 26 MRCNS, only mecR1A-positive pattern (type lll) was detected in 53.6% of MRSA and 46.4% of MRCNS. The mecR1 (mecR1A and mecR1B) and mecI-positive pattern (type l) were detected in 42.3% of MRSA and 38.5% of MRCNS. In 19.2% of MRCNS was type lV in which no mec regulator genes were detected. Our results showed that a greater genomic variation existed in MRCNS than a MRSA. Results in direct sequencing of mecI revealed that mecI gene tested in our study did not harbour mutations and deletions. There was no correlation between the level of resistance and the presence or absence of mec regulator genes. CONCLUSION: The induction of methicillin resistance and the variability of phenotypic expression of methicillin resistance suggested that additional factors on the chromosome are involved.