Aspectos Epidemiológicos Del Cáncer De Hígado en Costa Rica Años 1990-2014

Today, liver cancer involvement has become more relevant, as globally and more specifically in the Americas, there has been an increase in liver cancer, which is not inconsiderable as a cause of global mortality. Liver cancer represents a pathology that affects various population groups worldwide, with hepatocellular carcinoma being the most common. While it is true that liver cancer was not included in the main cancers with the highest incidence in Costa Rica, primary liver cancer is said to be a major health problem worldwide. In Costa Rica during the period 1990 to 2014, there was a greater involvement by liver cancer in men, the hepatitis C virus presented the highest mortality rate as a cause of this condition, followed by liquor consumption and other causes. The age group with the highest mortality rate was the population over the age of 70. The overall mortality rate showed a noticeable decrease; however, compared to other Latin American countries the rate in Costa Rica is higher, similar to that of the United States. The epidemiological characteristics analyzed showed in their rates a tendency to decline. Both incidence rate and prevalence over the 25 years of study showed higher male than female numbers.En la actualidad la afectación por cáncer de hígado ha adquirido una mayor relevancia, ya que a nivel mundial y más específicamente en el Continente Americano, se ha notado un incremento en dicha patología, la cual llega a ocupar un lugar no despreciable como causa de mortalidad a nivel mundial. El cáncer de hígado representa una patología que afecta diversos grupos poblacionales a nivel mundial, siendo el carcinoma hepatocelular el más frecuente. Si bien es cierto que el cáncer de hígado no estaba incluido dentro de los principales tipos de cáncer con mayor incidencia en Costa Rica, se dice que a nivel mundial el cáncer de hígado primario es un problema de salud importante. En Costa Rica durante el período de 1990 al 2014, se presentó una mayor afectación por cáncer de hígado en los hombres, el virus de la hepatitis C presentó la tasa más alta de mortalidad como causa de este padecimiento, seguido de consumo de licor y otras causas. El grupo etario con la mayor tasa de mortalidad fue la población mayor de 70 años. La tasa general de mortalidad mostró una notoria disminución; sin embargo, en comparación con otros países latinoamericanos la tasa en Costa Rica es superior, siendo similar a la de Estados Unidos. Las características epidemiológicas analizadas, mostraron en sus tasas una tendencia a la disminución. Tanto la tasa de incidencia como de prevalencia a lo largo de los 25 años de estudio mostraron cifras mayores en el sexo masculino que en el sexo femenino

Brucella Genetic Variability in Wildlife Marine Mammals Populations Relates to Host Preference and Ocean Distribution

Intracellular bacterial pathogens probably arose when their ancestor adapted from a free-living environment to an intracellular one, leading to clonal bacteria with smaller genomes and less sources of genetic plasticity. Still, this plasticity is needed to respond to the challenges posed by the host. Members of the Brucella genus are facultative-extracellular intracellular bacteria responsible for causing brucellosis in a variety of mammals. The various species keep different host preferences, virulence, and zoonotic potential despite having 97–99% similarity at genome level. Here, we describe elements of genetic variation in Brucella ceti isolated from wildlife dolphins inhabiting the Pacific Ocean and the Mediterranean Sea. Comparison with isolates obtained from marine mammals from the Atlantic Ocean and the broader Brucella genus showed distinctive traits according to oceanic distribution and preferred host. Marine mammal isolates display genetic variability, represented by an important number of IS711 elements as well as specific IS711 and SNPs genomic distribution clustering patterns. Extensive pseudogenization was found among isolates from marine mammals as compared with terrestrial ones, causing degradation in pathways related to energy, transport of metabolites, and regulation/ transcription. Brucella ceti isolates infecting particularly dolphin hosts, showed further degradation of metabolite transport pathways as well as pathways related to cell wall/membrane/envelope biogenesis and motility. Thus, gene loss through pseudogenization is a source of genetic variation in Brucella, whichinturn, relates to adaptation to different hosts.This is relevant to understand the natural history of bacterial diseases, their zoonotic potential, and the impact of human interventions such as domestication.Comisión Nacional para la Gestión de la Biodiversidad/[R-028-203-OT]/CONAGEBIO/Costa RicaMinisterio de Ciencia, Tecnología y Telecomunicaciones/[FV-004-13]/MICITT/Costa RicaWellcome Trust/[098051]/WT/LondresWellcome Trust/[106690/Z/14/Z]/WT/LondresUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

A Sinorhizobium meliloti and Agrobacterium tumefaciens ExoR ortholog is not crucial for Brucella abortus virulence

Brucella is a facultative extracellular-intracellular pathogen that belongs to the Alphaproteo- bacteria class. Precise sensing of environmental changes and a proper response mediated by a gene expression regulatory network are essential for this pathogen to survive. The plant-related Alphaproteobacteria Sinorhizobium meliloti and Agrobacterium tumefaciens also alternate from a free to a host-associated life, where a regulatory invasion switch is needed for this transition. This switch is composed of a two-component regulatory system (TCS) and a global inhibitor, ExoR. In B. abortus, the BvrR/BvrS TCS is essential for intra- cellular survival. However, the presence of a TCS inhibitor, such as ExoR, in Brucella is still unknown. In this work, we identified a genomic sequence similar to S. meliloti exoR in the B. abortus 2308W genome, constructed an exoR mutant strain, and performed its characteri- zation through ex vivo and in vivo assays. Our findings indicate that ExoR is related to the BvrR phosphorylation state, and is related to the expression of known BvrR/BrvS gene tar- gets, such as virB8, vjbR, and omp25 when grown in rich medium or starving conditions. Despite this, the exoR mutant strain showed no significant differences as compared to the wild-type strain, related to resistance to polymyxin B or human non-immune serum, intracel- lular replication, or infectivity in a mice model. ExoR in B. abortus is related to BvrR/BvrS as observed in other Rhizobiales; however, its function seems different from that observed for its orthologs described in A. tumefaciens and S. meliloti.Brucella es un patógeno extracelular-intracelular facultativo que pertenece a la clase de las alfaproteobacterias. Para que este patógeno sobreviva, es esencial que detecte con precisión los cambios ambientales y dé una respuesta adecuada mediada por una red de regulación de la expresión génica. Las alfaproteobacterias Sinorhizobium meliloti y Agrobacterium tumefaciens, relacionadas con las plantas, también alternan entre una vida libre y otra asociada al hospedador, y para esta transición es necesario un interruptor regulador de la invasión. Este interruptor está compuesto por un sistema regulador de dos componentes (TCS) y un inhibidor global, ExoR. En B. abortus, el TCS BvrR/BvrS es esencial para la supervivencia intracelular. supervivencia intracelular. Sin embargo, la presencia de un inhibidor del TCS, como ExoR, en Brucella es aún desconocida. En este trabajo, identificamos una secuencia genómica similar a la de ExoR de S. meliloti en el genoma de B.abortus 2308W, construimos una cepa mutante de ExoR y realizamos su caracterización mediante ensayos ex vivo e in vivo. Nuestros resultados indican que ExoR está relacionado con la estado de fosforilación de BvrR, y está relacionado con la expresión de objetivos génicos conocidos de BvrR/BrvS, como virB8, vjbR y omp25 cuando se cultiva en medio rico o en condiciones de inanición. A pesar de esto, la cepa mutante exoR no mostró diferencias significativas en comparación con la cepa de tipo salvaje, relacionadas con la resistencia a la polimixina B o al suero humano no inmune, la replicación intracelular o la infectividad en un modelo de ratón. El ExoR en B. abortus está relacionado con el BvrR/BvrS como como se ha observado en otros Rhizobiales; sin embargo, su función parece diferente de la observada para sus ortólogos descritos en A. tumefaciens y S. meliloti.This work was supported by Fondos del Sistema FEES/CONARE [02-2020, 0652-19 to C. G-V], Fondos FIDA, Universidad Nacional [SIA 0047-17 to C. G-V], Espacio Universitario de Estudios Avanzados, UCREA [B8762] from the Presidency of University of Costa Rica, and the Vice Presidency for Research, University of Costa Rica [C0456 to E.C-O]. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.Escuela de Medicina Veterinari

Brucella abortus senses the intracellular environment through the BvrR/Bvrs two-component system, which allows B. abortus to adapt to its replicative nich

Brucella abortus is a facultative extracellular-intracellular pathogen belonging to a group of Alphaproteobacteria that establishes close interactions with animal cells. This bacterium enters host cells in a membrane-bound compartment, avoiding the lysosomal route and reaching the endoplasmic reticulum through the action of the type IV secretion system, VirB. In this work, we demonstrate that the BvrR/BvrS two-component system senses the intracellular environment to mount the transcriptional response required for intracellular life adaptation. By combining a method to purify intracellularly extracted bacteria with a strategy that allows direct determination of BvrR phosphorylation, we showed that upon entrance to host cells, the regulatory protein BvrR was activated (BvrR-P) by phosphorylation at aspartate 58. This activation takes place in response to intracellular cues found in early compartments, such as low pH and nutrient deprivation. Furthermore, BvrR activation was followed by an increase in the expression of VjbR and VirB. The in vitro activation of this BvrR-P/VjbR/VirB virulence circuit rescued B. abortus from the inhibition of intracellular replication induced by bafilomycin treatment of cells, demonstrating the relevance of this mechanism for intracellular bacterial survival and replication. All together, our results indicate that B. abortus senses the transition from the extracellular to the intracellular milieu through BvrR/BvrS, allowing the bacterium to transit safely to its replicative niche. These results serve as a working model for understanding the role of this family of two-component systems in the adaptation to intracellular life of AlphaproteobacteriaBrucella abortus es un patógeno facultativo extracelular-intracelular perteneciente a un grupo de alfaproteobacterias que establece estrechas interacciones con las células animales. Esta bacteria entra en las células huéspedes en un compartimento unido a la membrana, evitando la ruta lisosómica y llegando al retículo endoplásmico por la acción del sistema de secreción de tipo IV, VirB. En este trabajo, demostramos que el sistema de dos componentes BvrR/BvrS detecta el entorno intracelular para montar la respuesta transcripcional necesaria para la adaptación de la vida intracelular. Combinando un método para purificar las bacterias extraídas intracelularmente con una estrategia que permite la determinación directa de la fosforilación de BvrR, demostramos que al entrar en las células huéspedes, la proteína reguladora BvrR fue activada (BvrR-P) por la fosforilación en el aspartato 58. Esta activación tiene lugar en respuesta a las señales intracelulares encontradas en los primeros compartimentos, como el bajo pH y la privación de nutrientes. Además, a la activación de BvrR le siguió un aumento de la expresión de VjbR y VirB. La activación in vitro de este circuito de virulencia BvrR-P/VjbR/VirB rescató a B. abortus de la inhibición de la replicación intracelular inducida por el tratamiento de las células con bafilomicina, lo que demuestra la importancia de este mecanismo para la supervivencia y la replicación de las bacterias intracelulares. En conjunto, nuestros resultados indican que B. abortus percibe la transición del medio extracelular al intracelular a través de BvrR/BvrS, permitiendo a la bacteria transitar con seguridad a su nicho de replicación. Estos resultados sirven como modelo de trabajo para comprender el papel de esta familia de sistemas de dos componentes en la adaptación a la vida intracelular de las alfaproteobacterias.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari

Senses the Intracellular Environment through the BvrR/BvrS Two-Component System, Which Allows To Adapt to Its Replicative Niche

Brucella abortus is a facultative extracellular-intracellular pathogen belonging to a group of Alphaproteobacteria that establishes close interactions with animal cells. This bacterium enters host cells in a membrane-bound compartment, avoiding the lysosomal route and reaching the endoplasmic reticulum through the action of the type IV secretion system, VirB. In this work, we demonstrate that the BvrR/BvrS two-component system senses the intracellular environment to mount the transcriptional response required for intracellular life adaptation. By combining a method to purify intracellularly extracted bacteria with a strategy that allows direct determination of BvrR phosphorylation, we showed that upon entrance to host cells, the regulatory protein BvrR was activated (BvrR-P) by phosphorylation at aspartate 58. This activation takes place in response to intracellular cues found in early compartments, such as low pH and nutrient deprivation. Furthermore, BvrR activation was followed by an increase in the expression of VjbR and VirB. The in vitro activation of this BvrR-P/VjbR/VirB virulence circuit rescued B. abortus from the inhibition of intracellular replication induced by bafilomycin treatment of cells, demonstrating the relevance of this mechanism for intracellular bacterial survival and replication. All together, our results indicate that B. abortus senses the transition from the extracellular to the intracellular milieu through BvrR/BvrS, allowing the bacterium to transit safely to its replicative niche. These results serve as a working model for understanding the role of this family of two-component systems in the adaptation to intracellular life of Alphaproteobacteria.Universidad de Costa Rica/[803-B3-761]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

Senses the Intracellular Environment through the BvrR/BvrS Two-Component System, Which Allows To Adapt to Its Replicative Niche

Brucella abortus is a facultative extracellular-intracellular pathogen belonging to a group of Alphaproteobacteria that establishes close interactions with animal cells. This bacterium enters host cells in a membrane-bound compartment, avoiding the lysosomal route and reaching the endoplasmic reticulum through the action of the type IV secretion system, VirB. In this work, we demonstrate that the BvrR/BvrS two-component system senses the intracellular environment to mount the transcriptional response required for intracellular life adaptation. By combining a method to purify intracellularly extracted bacteria with a strategy that allows direct determination of BvrR phosphorylation, we showed that upon entrance to host cells, the regulatory protein BvrR was activated (BvrR-P) by phosphorylation at aspartate 58. This activation takes place in response to intracellular cues found in early compartments, such as low pH and nutrient deprivation. Furthermore, BvrR activation was followed by an increase in the expression of VjbR and VirB. The in vitro activation of this BvrR-P/VjbR/VirB virulence circuit rescued B. abortus from the inhibition of intracellular replication induced by bafilomycin treatment of cells, demonstrating the relevance of this mechanism for intracellular bacterial survival and replication. All together, our results indicate that B. abortus senses the transition from the extracellular to the intracellular milieu through BvrR/BvrS, allowing the bacterium to transit safely to its replicative niche. These results serve as a working model for understanding the role of this family of two-component systems in the adaptation to intracellular life of Alphaproteobacteria.Universidad de Costa Rica/[803-B3-761]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

Public 2308W annotation

This is an editable version of B. abortus 2308W. The aim of this document is to provide a simple mechanism for updates in genes annotation.Esta es una versión editable de B. abortus 2308W. El objetivo de este documento es proporcionar un mecanismo simple para las actualizaciones en la anotación de genes.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari