ABSTRACT
Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA) that methylates K14 of histone H3 (H3K14me3) to counteract host immune responses. However, it is not known how L. pneumophila infection catalyses H3K14 methylation as this residue is usually acetylated. Here we show that L. pneumophila secretes a eukaryotic-like histone deacetylase (LphD) that specifically targets H3K14ac and works in synergy with RomA. Both effectors target host chromatin and bind the HBO1 histone acetyltransferase complex that acetylates H3K14. Full activity of RomA is dependent on the presence of LphD as H3K14 methylation levels are significantly decreased in a ∆lphD mutant. The dependency of these two chromatin-modifying effectors on each other is further substantiated by mutational and virulence assays revealing that the presence of only one of these two effectors impairs intracellular replication, while a double knockout (∆lphD∆romA) can restore intracellular replication. Uniquely, we present evidence for "para-effectors", an effector pair, that actively and coordinately modify host histones to hijack the host response. The identification of epigenetic marks modulated by pathogens has the potential to lead to the development of innovative therapeutic strategies to counteract bacterial infection and strengthening host defences.
Subject(s)
Legionella pneumophila , Legionella , Legionnaires' Disease , Humans , Legionella/metabolism , Chromatin/metabolism , Bacterial Proteins/metabolism , Legionnaires' Disease/genetics , Histones/metabolismABSTRACT
Se presentan algunos de los resultados de la etapa cuantitativa de un estudio mixto en el cual se combinó la metodología cualitativa y la cuantitativa. La etapa cuantitativa consistió en un diseño descriptivo correlacional cuyo objetivo fue establecer la asociación entre la intención de usar anticonceptivos artificiales (modernos) y algunas variables psicosociales: metas personales futuras, percepción del rol de género, severidad atribuida al embarazo en la adolescencia, vulnerabilidad de llegar a embarazarse, barreras percibidas para acercarse al consultorio; riesgo social atribuible a la condición de embarazo durante la adolescencia, uso de anticonceptivos artificiales (A.A.) entre las amigas, consejo otorgado por las amigas, y número de parejas. Se administró una encuesta a un total de 260 adolescentes embarazadas de estrato social bajo asistentes a control de embarazo. Los datos muestran asociación significativa entre la intención de usar A.A. y las metas a mediano plazo, el consejo otorgado por las amigas en relación al uso de A.A. y orientación femenina en el rol de género. Contrario a lo esperado, el uso de A.A. por parte de las amigas no se encuentra asociado a la intención que expresan de usarlos, tampoco en las adolescentes la percepción de las barreras para acercarse al consultorio constituye un impedimento en su intención de usar A.A. Aún cuando las adolescentes reconocen que existe un riesgo social al embarazarse atribuible a la reacción social ante un embarazo, esta variable no es lo suficientemente importante en su intención de usar A.A.
In the present work some of the results from the quantitative stage of a combined study merging quantitative and qualitative methodologies are presented. The quantitative stage consisted of a correlational descriptive design aiming at establishing the association between the intention to use artificial contraceptives (modern) and some psychosocial variables: future individual goals, gender role perception, the stressfulness and severity attributed to the situation of pregnancy during adolescence, the vulnerability derived of becoming pregnant, the perceived barriers to attend outpatient clinics, social risk attributed to the condition of being pregnant during adolescence, use of artificial contraceptives (AA) among friends, friend counseling and partner number. A survey was implemented among 260 pregnant adolescents from a low social stratum that were under pregnancy follow up. Data showed a significant association between the intent to use contraceptives and the medium term goals, friend counseling with regard to the use of contraceptives and female orientation in gender role. Unlike the expected, the use of AA by friends did not correlate to the intention to use they expressed. The perception of barriers to attend outpatient clinics by adolescents did not represent an impediment to their intention to use AA. Although adolescents acknowledge there is a social risk upon becoming pregnant that can be attributed to the social reaction before a pregnancy, such variable is not significant enough for their intention to use AA.
