Regulatory Evolution Drives Evasion of Host Inflammasomes by Salmonella Typhimurium
Por:
Ilyas, Bushra, Mulder, David T., Little, Dustin J., Elhenawy, Wael, Banda, Maria M., Perez-Morales, Deyanira, Tsai, Caressa N., Chau, N. Y. E., Bustamante, Victor H., Coombes, Brian K.
Publicada:
23 oct 2018
Categoría:
Biochemistry, genetics and molecular biology (miscellaneous)
Resumen:
Bacterial two-component regulatory systems (TCS) couple the detection of
niche-specific cues with adaptive gene expression to optimize fitness.
In Salmonella Typhimurium (STM), the SsrA-SsrB TCS regulates virulence
genes needed for survival within host cells, yet the impact of this TCS
on regulatory evolution in this pathogen remains incompletely
understood. Here, we show that SsrB alters a transcriptional network
controlling bacterial motility to limit inflammasome activation during
host cell infection. Using comparative RNA sequencing between STM and S.
bongori (SBG) engineered to express SsrB, we show that SsrB represses
flagellar gene expression in STM but activates this pathway in SBG,
which has evolved in the absence of SsrB. Motility repression in STM is
driven by an SsrB-binding region upstream of flhDC that appears to have
evolved in STM following divergence from SBG. These data reveal a
divergent regulatory circuit in non-coding DNA that reduces flagellar
gene expression to evade host defenses.
Filiaciones:
McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4L8, Canada
McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8S 4L8, Canada
Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Microbiol Mol, Cuernavaca, Morelos, Mexico
Univ Autonoma Estado Morelos, Ctr Invest Biotecnol, CONACYT, Cuernavaca, Morelos, Mexico
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