ESX-3 secretion system in Mycobacterium: An overview.

Mycobacteria are microorganisms distributed in the environment worldwide, and some of them, such as Mycobacterium tuberculosis or M. leprae, are pathogenic. The hydrophobic mycobacterial cell envelope has low permeation and bacteria need to export products across their structure. Mycobacteria possess specialized protein secretion systems, such as the Early Secretory Antigenic Target 6 secretion (ESX) system. Five ESX loci have been described in M. tuberculosis, called ESX-1 to ESX-5. The ESX-3 secretion system has been associated with mycobacterial metabolism and growth. The locus of this system is highly conserved across mycobacterial species. Metallo-proteins regulate negative ESX-3 transcription in high conditions of iron and zinc. Moreover, this secretion system is part of an antioxidant regulatory pathway linked to Zinc. EccA3, EccB3, EccC3, EccD3, and EccE3 are components of the ESX-3 secretion machinery, whereas EsxG-EsxH, PE5-PPE4, and PE15-PPE20 are proteins secreted by this system. In addition, EspG3 and MycP3 are complementary proteins involved in transport and proteolysis respectively. This system is associated to mycobacterial virulence by releasing the bacteria from the phagosome and inhibiting endomembrane damage response. Furthermore, components of this system inhibit the host immune response by reducing the recognition of M. tuberculosis-infected cells. The components of the ESX-3 secretion system play a role in drug resistance and cell wall integrity. Moreover, the expression data of this system indicated that external and internal factors affect ESX-3 locus expression. This review provides an overview of new findings on the ESX-3 secretion system, its regulation, expression, and functions.

[Spatial modeling of leprosy in the state of Bahia, Brazil, (2001-2015) and social determinants of health]. / Modelagem espacial da hanseníase no estado da Bahia, Brasil, (2001-2015) e determinantes sociais da saúde.

This work analyzes the spatial distribution of leprosy in Bahia and associated social determinants. It is an ecological study, with leprosy data from 2001-2015. Three epidemiological indicators were selected: coefficient of detection in the general population and in children under 15 and the rate of new cases with grade II physical disability. These indicators were flattened by the Local Empirical Bayesian Model and Global and Local Moran statistics were applied. The independent variables were selected from the IBGE-2010 Census. Multivariate regressions were employed, followed by spatial regression. Leprosy exhibited a heterogeneous distribution in the state, with concentration in the north-west axis and the south region. For the general detection coefficient, five variables composed the final model: demographic density, urban population proportion, per capita income, proportion of extremely poor and households with over three people per dormitory. The illiteracy proportion made up the final model for the grade II rate of physical disability. No determinants of the occurrence of the disease were identified in children under 15. The modeling used contributed to demonstrate the spatial heterogeneity and social determinants of the disease in Bahia, revealing the complexity of the problem.

O trabalho analisa a distribuição espacial da hanseníase na Bahia e os determinantes sociais relacionados. Estudo ecológico com dados de hanseníase do período 2001-2015. Três indicadores epidemiológicos foram selecionados: coeficiente de detecção na população geral e em menores de 15 anos e a taxa de casos novos com grau II de incapacidade. Os indicadores foram suavizados pelo Modelo Bayesiano Empírico Local e aplicou-se estatística de Moran Global e Local. As variáveis independentes foram selecionadas a partir do Censo IBGE-2010. Regressões multivariadas foram empregadas, seguidas de regressão espacial. Observou-se distribuição heterogênea no estado, com concentração no eixo norte-oeste e região sul. Para o coeficiente de detecção geral, cinco variáveis compuseram o modelo: densidade demográfica, proporção da população urbana, renda per capita, proporção de extremamente pobres e domicílios com mais de três pessoas por dormitório. A proporção de analfabetismo compôs o modelo final para a taxa de grau II de incapacidade física. Não foram identificados determinantes da ocorrência da doença em menores de 15 anos. A modelagem utilizada contribuiu para demonstrar a heterogeneidade espacial e os determinantes sociais da doença na Bahia, colocando em evidência a complexidade do problema.

Leprosy and social deprivation: Definition of priority areas in an endemic state Northeastern Brazil. / Hanseníase e carência social: definição de áreas prioritárias em estado endêmico do Nordeste brasileiro.

INTRODUCTION: Leprosy is a disease that reserves close relation with social and economic conditions. Brazil is the only country that has not yet reached the goal of eliminating the disease as a public health problem. OBJECTIVE: This study aimed to analyze social deprivation in the municipalities of Bahia and its relation with the detection of new cases of leprosy in the population. METHODS: It is an ecological study conducted in the state of Bahia, from 2001 to 2015. Variables analyzed: detection rate of new cases, social deprivation index (SDI) and Hansen's disease in children under 15 years of age. The SDI was built on four variables: socioeconomic performance index, per capita income, proportion of extremely poor, and household density. For spatial analysis, local empirical bayesian modeling and global and local Moran statistics were used. Statistical analysis used multivariate, spatial and logistic regression, odds ratio calculation and analysis of variance. RESULTS: Leprosy showed heterogeneous distribution in the state, with concentration in the north-west and south axis. 60.4% (n = 252) of the municipalities presented very low life conditions. An association was observed between living conditions and the detection of leprosy, with higher coefficients in the municipality group with better living conditions (p < 0.001). CONCLUSION: It was concluded that the worst conditions acted as an impediment to the diagnosis, while increasing the risk of illness. Good conditions have the opposite effect.

INTRODUÇÃO: A hanseníase é uma doença que guarda estreita relação com as condições sociais e econômicas. O Brasil é o único país que ainda não alcançou a meta de eliminação da doença como problema de saúde pública. OBJETIVO: Este trabalho teve como objetivo analisar a associação entre a carência social dos municípios baianos e a detecção de casos novos de hanseníase na população, como instrumento para a definição de áreas prioritárias para intervenção. METODOLOGIA: Trata-se de um estudo ecológico realizado no estado da Bahia, no período de 2001 a 2015. Variáveis analisadas: coeficiente de detecção casos novos, índice de carência social (ICS) e hanseníase em menores de 15 anos. O ICS foi construído com base em quatro variáveis: índice de performance socioeconômica, renda per capita, proporção de extremamente pobres e densidade domiciliar. Na análise espacial, foram utilizadas modelagem bayesiana empírica local e estatística de Moran global e local. Na análise estatística, foram empregados regressão multivariada, espacial e logística, cálculo do odds ratio e análise de variância. RESULTADOS: A hanseníase apresentou distribuição heterogênea no estado, com concentração no eixo norte-oeste e sul. Dos municípios, 60,4% (n = 252) apresentaram muito baixa condição de vida. Observou-se associação entre as condições de vida e a detecção da hanseníase, com maiores coeficientes no grupo de município com melhor condição de vida (p < 0,001). CONCLUSÃO: As piores condições atuaram como um impeditivo ao diagnóstico, ao mesmo tempo que ampliaram o risco de adoecimento. As boas condições possuem efeito inverso.

Hanseníase e carência social: definição de áreas prioritárias em estado endêmico do Nordeste brasileiro / Leprosy and social deprivation: Definition of priority areas in an endemic state Northeastern Brazil

RESUMO: Introdução: A hanseníase é uma doença que guarda estreita relação com as condições sociais e econômicas. O Brasil é o único país que ainda não alcançou a meta de eliminação da doença como problema de saúde pública. Objetivo: Este trabalho teve como objetivo analisar a associação entre a carência social dos municípios baianos e a detecção de casos novos de hanseníase na população, como instrumento para a definição de áreas prioritárias para intervenção. Metodologia: Trata-se de um estudo ecológico realizado no estado da Bahia, no período de 2001 a 2015. Variáveis analisadas: coeficiente de detecção casos novos, índice de carência social (ICS) e hanseníase em menores de 15 anos. O ICS foi construído com base em quatro variáveis: índice de performance socioeconômica, renda per capita, proporção de extremamente pobres e densidade domiciliar. Na análise espacial, foram utilizadas modelagem bayesiana empírica local e estatística de Moran global e local. Na análise estatística, foram empregados regressão multivariada, espacial e logística, cálculo do odds ratio e análise de variância. Resultados: A hanseníase apresentou distribuição heterogênea no estado, com concentração no eixo norte-oeste e sul. Dos municípios, 60,4% (n = 252) apresentaram muito baixa condição de vida. Observou-se associação entre as condições de vida e a detecção da hanseníase, com maiores coeficientes no grupo de município com melhor condição de vida (p < 0,001). Conclusão: As piores condições atuaram como um impeditivo ao diagnóstico, ao mesmo tempo que ampliaram o risco de adoecimento. As boas condições possuem efeito inverso.

ABSTRACT: Introduction: Leprosy is a disease that reserves close relation with social and economic conditions. Brazil is the only country that has not yet reached the goal of eliminating the disease as a public health problem. Objective: This study aimed to analyze social deprivation in the municipalities of Bahia and its relation with the detection of new cases of leprosy in the population. Methods: It is an ecological study conducted in the state of Bahia, from 2001 to 2015. Variables analyzed: detection rate of new cases, social deprivation index (SDI) and Hansen's disease in children under 15 years of age. The SDI was built on four variables: socioeconomic performance index, per capita income, proportion of extremely poor, and household density. For spatial analysis, local empirical bayesian modeling and global and local Moran statistics were used. Statistical analysis used multivariate, spatial and logistic regression, odds ratio calculation and analysis of variance. Results: Leprosy showed heterogeneous distribution in the state, with concentration in the north-west and south axis. 60.4% (n = 252) of the municipalities presented very low life conditions. An association was observed between living conditions and the detection of leprosy, with higher coefficients in the municipality group with better living conditions (p < 0.001). Conclusion: It was concluded that the worst conditions acted as an impediment to the diagnosis, while increasing the risk of illness. Good conditions have the opposite effect.

Spatial modeling of leprosy in the state of Bahia and its social determinants: a study of health inequities.

BACKGROUND: Leprosy is a neglected disease caused by Mycobacterium leprae. Brazil has the second largest number of cases in the world. OBJECTIVES: To analyze the spatial distribution of leprosy in the state of BAHIA, Brazil, and the association between his occurrence and the synthetic indicators of municipal socioeconomic performance, social vulnerability and income inequality. METHODS: An ecological study with secondary data obtained from the National System of Notifiable Diseases. Dependent variables: coefficient of detection in the general population and in the population under 15 years old and the rate of grade II of physical disability. Independent variables: Synthetic indicators of socioeconomic performance, social vulnerability and income inequality. RESULTS: The highest coefficients of detection of new cases in the general population and in children under 15 years old are concentrated in the north-west axis and in the southern region of the state. On the other hand, the highest rates of degree II of physical incapacity are concentrated in the north, northeast and south regions. Only the Index of Social and Economic Performance(IPESE)-Economy and Finance composed the final regression model of the general detection coefficients and in children under 15 years old. The municipalities with the highest indexes had the highest detection coefficients, reflecting the capacity to diagnose new cases. STUDY LIMITATIONS: The use of synthetic indicators is a limitation of the study. CONCLUSIONS: Leprosy presents a heterogeneous spatial pattern in the state of BAHIA, and the IPESE-Economics and Finance indicator is the only one with explanatory potential of the disease.

Leprosy transmission in Bahia, 2001-2015: modeling based on Jointpoint regression and spatial scan statistics. / Transmissão da hanseníase na Bahia, 2001-2015: modelagem a partir de regressão por pontos de inflexão e estatística de varredura espacial.

OBJECTIVE: to describe the trend and the spatial distribution of leprosy in the state of Bahia, Brazil, 2001-2015. METHODS: this was a mixed ecological study of epidemiological indicators of leprosy; Jointpoint regression was used for the temporal analysis, while spatial scan statistics were used to identify clusters of the disease; the trend was classified as stationary, increasing or decreasing; we calculated the annual percent change (APC) and average annual percent change (AAPC). RESULTS: there was a reduction in prevalence (AAPC = -5.6; p<0,001), treatment dropout (AAPC = -13.7; p<0.001), and females with leprosy (AAPC = -0.6; p<0.001); the new grade II case coefficient (AAPC = 2.7; p<0.001) and the proportion of multibacillary cases (AAPC = 2,2; p<0.001) showed a growing trend; spatial distribution was heterogeneous and concentrated in three regions in particular (north, west and south of the state), with variation between the indicators. CONCLUSION: persisting leprosy transmission in the state, late diagnosis and high hidden prevalence is suggested.

Spatial modeling of leprosy in the state of Bahia and its social determinants: a study of health inequities

Abstract BACKGROUND: Leprosy is a neglected disease caused by Mycobacterium leprae. Brazil has the second largest number of cases in the world. OBJECTIVES: To analyze the spatial distribution of leprosy in the state of BAHIA, Brazil, and the association between his occurrence and the synthetic indicators of municipal socioeconomic performance, social vulnerability and income inequality. METHODS: An ecological study with secondary data obtained from the National System of Notifiable Diseases. Dependent variables: coefficient of detection in the general population and in the population under 15 years old and the rate of grade II of physical disability. Independent variables: Synthetic indicators of socioeconomic performance, social vulnerability and income inequality. RESULTS: The highest coefficients of detection of new cases in the general population and in children under 15 years old are concentrated in the north-west axis and in the southern region of the state. On the other hand, the highest rates of degree II of physical incapacity are concentrated in the north, northeast and south regions. Only the Index of Social and Economic Performance(IPESE)-Economy and Finance composed the final regression model of the general detection coefficients and in children under 15 years old. The municipalities with the highest indexes had the highest detection coefficients, reflecting the capacity to diagnose new cases. STUDY LIMITATIONS: The use of synthetic indicators is a limitation of the study. CONCLUSIONS: Leprosy presents a heterogeneous spatial pattern in the state of BAHIA, and the IPESE-Economics and Finance indicator is the only one with explanatory potential of the disease.

Transmissão da hanseníase na Bahia, 2001-2015: modelagem a partir de regressão por pontos de inflexão e estatística de varredura espacial / Transmisión de la lepra en Bahia, 2001-2015: modelado a partir de regresión por Joinpoint y estadística de barrido espacial / Leprosy transmission in Bahia, 2001-2015: modeling based on Jointpoint regression and spatial scan statistics

Objetivo: descrever a tendência e a distribuição espacial da hanseníase no estado da Bahia, Brasil, em 2001-2015. Métodos: estudo ecológico misto dos indicadores epidemiológicos da hanseníase; na análise temporal, utilizou-se a regressão Joinpoint, e a estatística de varredura espacial na identificação de clusters da doença; a tendência foi classificada como estacionária, crescente ou decrescente; calculou-se a variação percentual anual (APC: annual percent change) e a variação percentual anual média (AAPC: average annual percent change). Resultados: houve redução da prevalência (AAPC = -5,6; p<0,001), do abandono (AAPC = -13,7; p<0,001) e de mulheres doentes (AAPC = -0,6; p<0,001); o coeficiente de casos novos de grau II (AAPC = 2,7; p<0,001) e a proporção de casos multibacilares (AAPC = 2,2; p<0,001) apresentaram tendência crescente; revelou-se distribuição espacial heterogênea, concentrada em três regiões destacadas (norte, oeste e sul do estado), e variação entre indicadores. Conclusão: sugere-se persistência da transmissão da hanseníase no estado, diagnóstico tardio e elevada prevalência oculta.

Objetivo: describir la tendencia y distribución espacial de la lepra en el estado de Bahia, Brasil, en 2001-2015. Métodos: estudio ecológico mixto de los indicadores epidemiológicos de la lepra; se utilizó la regresión Joinpoint para el análisis temporal y la estadística espacial para la identificación de clusters de la enfermedad; la tendencia se clasificó en estacionaria, creciente o decreciente; se calculó el cambio porcentual anual (APC: annual percent change) y la variación porcentual anual promedio (AAPC: average annual percent change). Resultados: se ha reducido la prevalencia (AAPC = -5,6; p<0,001), el abandono (AAPC = -13,7; p<0,001) y las mujeres enfermas (AAPC = -0,6; p<0,001); la tasa de nuevos casos de grado II (AAPC = 2,7; p<0,001) y la proporción de casos multibacilares (AAPC = 2,2; p<0,001) presentaron una tendencia de crecimiento; la distribución espacial fue heterogénea, con concentración en tres regiones de destaque (norte, oeste y sur del estado) y variación entre indicadores. Conclusión: sugiere persistencia de la transmisión de la lepra en el estado, diagnóstico tardío y elevada prevalencia oculta.

Objective: to describe the trend and the spatial distribution of leprosy in the state of Bahia, Brazil, 2001-2015. Methods: this was a mixed ecological study of epidemiological indicators of leprosy; Jointpoint regression was used for the temporal analysis, while spatial scan statistics were used to identify clusters of the disease; the trend was classified as stationary, increasing or decreasing; we calculated the annual percent change (APC) and average annual percent change (AAPC). Results: there was a reduction in prevalence (AAPC = -5.6; p<0,001), treatment dropout (AAPC = -13.7; p<0.001), and females with leprosy (AAPC = -0.6; p<0.001); the new grade II case coefficient (AAPC = 2.7; p<0.001) and the proportion of multibacillary cases (AAPC = 2,2; p<0.001) showed a growing trend; spatial distribution was heterogeneous and concentrated in three regions in particular (north, west and south of the state), with variation between the indicators. Conclusion: persisting leprosy transmission in the state, late diagnosis and high hidden prevalence is suggested.

Proteomic changes in response to potassium starvation in the extremophilic yeast Debaryomyces hansenii.

In this work, we performed for the first time a proteomic approach to the processes induced by long-term potassium starvation in the halotolerant yeast Debaryomyces hansenii. The proteomic profile under this ionic stress conditions shows that important changes in gene expression take place as an adaptive response. We found a significant protein expression repression as well as metabolic changes such as the inhibition of the upper part of the glycolysis, the amino acid synthesis, and the Krebs cycle. On the other hand, genes related to stress responses, protein degradation, and sterols synthesis were upregulated in response to potassium deprivation. The findings in this study provide important information about how this particular yeast copes with ionic stress at molecular levels, which might further enrich the global understanding of salt tolerance processes in eukaryal systems and moreover highlighting the importance of the 'omics' approaches as a complement to the classical physiological studies.