Publication: Functional characterization of the effector protein SteA of "Salmonella" Typhimurium through heterologous expression in "Saccharomyces cerevisiae"
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2018-02-22
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Universidad Complutense de Madrid
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Abstract
Salmonella enterica es un patógeno bacteriano intracelular facultativo que causa una amplia variedad de enfermedades en humanos (Figueira & Holden, 2012). La virulencia de S. enterica se basa en la translocación de dos conjuntos de efectores bacterianos en las células huésped a través de sistemas de secreción de tipo 3 (T3SS) codificados por las 2 islas de patogenicidad SPI-1 y SPI-2. Los efectores del T3SS de la SPI-1 permiten a las bacterias invadir la célula huésped, mientras que los efectores del T3SS de la SPI-2 son responsables de la replicación intracelular y supervivencia de Salmonella dentro de una vacuola llamada Salmonella-containing vacuole (SCV) (Figueira y Holden, 2012; LaRock et al., 2015). SteA está entre el grupo de efectores de Salmonella que pueden ser translocados tanto por el T3SS de la SPI-1 como el de laSPI- 2 (Geddes et al., 2005; Cardenal-Muñoz y Ramos-Morales, 2011). Los mutantes carentes de este efector en S. Typhimurium muestran atenuación de la virulencia en modelos murinos de infección sistémica (Geddes et al., 2005, Lawley et al., 2006). Sin embargo, a pesar de su importancia para la patogénesis de S. Typhimurium, se han publicado pocos estudios sobre la función de SteA. Se ha descrito que SteA se localiza en la red trans-Golgi (TGN) cuando se expresa ectópicamente en células de mamífero no infectadas o se secreta por S. Typhimurium en células infectadas (Geddes et al., 2005). Sin embargo, en un estudio diferente, se demostró que el efector SteA translocado por la bacteria se localiza en los filamentos inducidos por Salmonella (SIFs) enriquecidos en el marcador del TGN 1,4-galactosiltransferasa (GalT) (Van Engelenburg & Palmer, 2010). Además, SteA contribuye al control de la dinámica de la membrana de la SCV y a la formación de SIFs, ya que las células infectadas con un mutante ΔsteA muestran menos SIFs, aumento de la agrupación de SCVs y vacuolas morfológicamente anormales que contienen más de una bacteria (Domingues et al., 2014)...
Salmonella enterica serovars are facultative intracellular bacterial pathogens causing a wide variety of diseases in humans (Figueira & Holden, 2012). S. enterica virulence relies on secreting two sets of bacterial effectors into host cells through the SPI-1 and SPI-2 T3SSs. SPI-1 effectors enable bacteria to invade the host cell while SPI-2 effectors are responsible for their intracellular replication and survival within the Salmonella-containing vacuole (SCV) (Figueira & Holden, 2012; Ramos-Morales, 2012; LaRock et al., 2015). SteA is among the group of Salmonella effectors that can be translocated by both the SPI-1 and the SPI-2 T3SSs (Geddes et al., 2005; Cardenal- Munoz & Ramos-Morales, 2011), and mutants lacking this effector in S. enterica serovar Typhimurium display virulence attenuation in mouse models of systemic infection (Geddes et al., 2005; Lawley et al., 2006). However, in spite of its importance for S. Typhimurium pathogenesis, only few studies on SteA function have been published. It has been reported that SteA localizes to the trans-Golgi network (TGN) when ectopically expressed in uninfected mammalian cells or delivered by S. Typhimurium into infected host cells (Geddes et al., 2005). However, in a different study, bacterially translocated SteA was shown to localize to Salmonella-induced tubules enriched in the TGN marker 1,4-galactosyltransferase (GalT) (Van Engelenburg & Palmer, 2010). In addition, SteA contributes to the control of SCV membrane dynamics and Salmonella-induced filaments (SIFs) formation, since cells infected with a ΔsteA mutant showed less SIFs, increased clustering of SCVs, and morphologically abnormal vacuoles containing more than one bacterium (Domingues et al., 2014)...
Salmonella enterica serovars are facultative intracellular bacterial pathogens causing a wide variety of diseases in humans (Figueira & Holden, 2012). S. enterica virulence relies on secreting two sets of bacterial effectors into host cells through the SPI-1 and SPI-2 T3SSs. SPI-1 effectors enable bacteria to invade the host cell while SPI-2 effectors are responsible for their intracellular replication and survival within the Salmonella-containing vacuole (SCV) (Figueira & Holden, 2012; Ramos-Morales, 2012; LaRock et al., 2015). SteA is among the group of Salmonella effectors that can be translocated by both the SPI-1 and the SPI-2 T3SSs (Geddes et al., 2005; Cardenal- Munoz & Ramos-Morales, 2011), and mutants lacking this effector in S. enterica serovar Typhimurium display virulence attenuation in mouse models of systemic infection (Geddes et al., 2005; Lawley et al., 2006). However, in spite of its importance for S. Typhimurium pathogenesis, only few studies on SteA function have been published. It has been reported that SteA localizes to the trans-Golgi network (TGN) when ectopically expressed in uninfected mammalian cells or delivered by S. Typhimurium into infected host cells (Geddes et al., 2005). However, in a different study, bacterially translocated SteA was shown to localize to Salmonella-induced tubules enriched in the TGN marker 1,4-galactosyltransferase (GalT) (Van Engelenburg & Palmer, 2010). In addition, SteA contributes to the control of SCV membrane dynamics and Salmonella-induced filaments (SIFs) formation, since cells infected with a ΔsteA mutant showed less SIFs, increased clustering of SCVs, and morphologically abnormal vacuoles containing more than one bacterium (Domingues et al., 2014)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Microbiología II, leída el 13-06-2017