Structure of a novel contractile injection system in Salmonella enterica subsp. salamae
(2025)- Abstract
- Extracellular contractile injection systems (eCISs) are phage-derived nanomachines used by bacteria to deliver effectors into target cells. Well-studied examples include the Photorhabdus asymbiotica virulence cassettes and the antifeeding prophage from Serratia entomophila, which have been engineered for heterologous cargo delivery. Recent genomic analyses identified previously uncharacterized eCIS gene clusters in the opportunistic human pathogen Salmonella enterica subspecies salamae, but their structure, function, and biotechnological potential remain unexplored. Here, we report a high-resolution cryo-electron microscopy structure of the S. enterica eCIS. Our atomic models reveal a unique sheath architecture, an expansive cage-like... (More)
- Extracellular contractile injection systems (eCISs) are phage-derived nanomachines used by bacteria to deliver effectors into target cells. Well-studied examples include the Photorhabdus asymbiotica virulence cassettes and the antifeeding prophage from Serratia entomophila, which have been engineered for heterologous cargo delivery. Recent genomic analyses identified previously uncharacterized eCIS gene clusters in the opportunistic human pathogen Salmonella enterica subspecies salamae, but their structure, function, and biotechnological potential remain unexplored. Here, we report a high-resolution cryo-electron microscopy structure of the S. enterica eCIS. Our atomic models reveal a unique sheath architecture, an expansive cage-like shell around a central spike, and an associated transmembrane hydrolase. We identify a putative effector encoded within the operon exhibiting periplasmic toxicity and provide evidence that the S. enterica eCIS deviates from canonical eCISs by interacting with the inner membrane. Guided by these structural features, we uncover a previously unannotated cluster of contractile injection systems (CISs). Together, our findings expand the known diversity of CIS structures and functions and lay the groundwork for engineering customizable protein delivery platforms. (Less)
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https://lup.lub.lu.se/record/f6ca43da-ca0a-44cd-b1e8-477d9ec6468e
- author
- organization
- publishing date
- 2025-06-02
- type
- Working paper/Preprint
- publication status
- published
- subject
- publisher
- bioRxiv
- DOI
- 10.1101/2025.06.01.657177
- language
- English
- LU publication?
- yes
- id
- f6ca43da-ca0a-44cd-b1e8-477d9ec6468e
- date added to LUP
- 2025-06-03 22:22:26
- date last changed
- 2025-06-04 08:48:25
@misc{f6ca43da-ca0a-44cd-b1e8-477d9ec6468e, abstract = {{Extracellular contractile injection systems (eCISs) are phage-derived nanomachines used by bacteria to deliver effectors into target cells. Well-studied examples include the Photorhabdus asymbiotica virulence cassettes and the antifeeding prophage from Serratia entomophila, which have been engineered for heterologous cargo delivery. Recent genomic analyses identified previously uncharacterized eCIS gene clusters in the opportunistic human pathogen Salmonella enterica subspecies salamae, but their structure, function, and biotechnological potential remain unexplored. Here, we report a high-resolution cryo-electron microscopy structure of the S. enterica eCIS. Our atomic models reveal a unique sheath architecture, an expansive cage-like shell around a central spike, and an associated transmembrane hydrolase. We identify a putative effector encoded within the operon exhibiting periplasmic toxicity and provide evidence that the S. enterica eCIS deviates from canonical eCISs by interacting with the inner membrane. Guided by these structural features, we uncover a previously unannotated cluster of contractile injection systems (CISs). Together, our findings expand the known diversity of CIS structures and functions and lay the groundwork for engineering customizable protein delivery platforms.}}, author = {{Ejaz, Rooshanie N. and Funke, Kristin and Kielkopf, Claudia S. and Martin, Freddie J.O. and Šiborová, Marta and Hendriks, Ivo A. and Sofos, Nicholas H. and Pape, Tillmann H. and Rebrova, Eva Maria and Nielsen, Michael L. and Erhardt, Marc and Taylor, Nicholas M. I.}}, language = {{eng}}, month = {{06}}, note = {{Preprint}}, publisher = {{bioRxiv}}, title = {{Structure of a novel contractile injection system in Salmonella enterica subsp. salamae}}, url = {{http://dx.doi.org/10.1101/2025.06.01.657177}}, doi = {{10.1101/2025.06.01.657177}}, year = {{2025}}, }