Regulatory Evolution Drives Evasion of Host Inflammasomes by Salmonella Typhimurium
Bushra Ilyas,
David T. Mulder,
Dustin J. Little,
Wael Elhenawy,
María M. Banda,
Deyanira Pérez-Morales,
Caressa N. Tsai,
N.Y.E. Chau,
Víctor H. Bustamante,
Brian K. Coombes
Affiliations
Bushra Ilyas
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada
David T. Mulder
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada
Dustin J. Little
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada
Wael Elhenawy
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada
María M. Banda
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
Deyanira Pérez-Morales
CONACYT, Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México
Caressa N. Tsai
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada
N.Y.E. Chau
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada
Víctor H. Bustamante
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
Brian K. Coombes
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada; Corresponding author
Summary: 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. : Bacterial pathogens tune their gene expression in certain host niches. Ilyas et al. identify an immune evasion mechanism evolved in S. enterica that couples repression of flagellar motility with host cell infection. Keywords: Salmonella, immune evasion, pathogenic adaptation, regulatory evolution, RNA-seq
