The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella
Por:
Pérez-Morales D., Banda M.M., Elizabeth Chau, N. Y., Salgado H., Martínez-Flores I., Antonio Ibarra, J., Ilyas B., Coombes B.K., Bustamante V.H.
Publicada:
1 jul 2017
Resumen:
The evolution of bacterial pathogenicity, heavily influenced by
horizontal gene transfer, provides new virulence factors and regulatory
connections that alter bacterial phenotypes. Salmonella pathogenicity
islands 1 and 2 (SPI-1 and SPI-2) are chromosomal regions that were
acquired at different evolutionary times and are essential for
Salmonella virulence. In the intestine of mammalian hosts, Salmonella
expresses the SPI-1 genes that mediate its invasion to the gut
epithelium. Once inside the cells, Salmonella down-regulates the SPI-1
genes and induces the expression of the SPI-2 genes, which favor its
intracellular replication. The mechanism by which the invasion machinery
is deactivated following successful invasion of host cells is not known.
Here, we show that the SPI-2 encoded transcriptional regulator SsrB,
which positively controls SPI-2, acts as a dual regulator that represses
expression of SPI-1 during intracellular stages of infection. The
mechanism of this SPI-1 repression by SsrB was direct and acts upon the
hilD and hilA regulatory genes. The phenotypic effect of this molecular
switch activity was a significant reduction in invasion ability of S.
enterica serovar Typhimurium while promoting the expression of genes
required for intracellular survival. During mouse infections, Salmonella
mutants lacking SsrB had high levels of hilA (SPI-1) transcriptional
activity whereas introducing a constitutively active SsrB led to
significant hilA repression. Thus, our results reveal a novel
SsrB-mediated mechanism of transcriptional crosstalk between SPI-1 and
SPI-2 that helps Salmonella transition to the intracellular lifestyle.
Filiaciones:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Microbiol Mol, Cuernavaca, Morelos, Mexico
Univ Autonoma Estado Morelos, Ctr Invest Biotecnol, CONACYT, Cuernavaca, Morelos, Mexico
McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON, Canada
McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON, Canada
Univ Nacl Autonoma Mexico, Programa Genom Computac, Ctr Ciencias Genom, Cuernavaca, Morelos, Mexico
Inst Politecn Nacl, Escuela Nacl Ciencias Biol, Dept Microbiol, Mexico City, DF, Mexico
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
CONACYT, Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada
Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico
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