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Related Concept Videos

Gram-negative Bacterial Protein Secretion Systems01:17

Gram-negative Bacterial Protein Secretion Systems

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Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
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Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...
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Bacterial conjugation is a mechanism of horizontal gene transfer that enables the exchange of genetic material between bacterial cells through direct contact. This process is facilitated by a donor cell carrying a conjugative plasmid, which encodes genes necessary for pilus formation, DNA replication, and transfer. The conjugative plasmid plays a central role in initiating and executing the transfer of genetic material.The tra region of the conjugative plasmid encodes proteins responsible for...
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Updated: Aug 5, 2025

Electroporation of Functional Bacterial Effectors into Mammalian Cells
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Programmable protein delivery with a bacterial contractile injection system.

Joseph Kreitz1,2,3,4,5, Mirco J Friedrich1,2,3,4,5, Akash Guru1,2,3,4,5

  • 1Howard Hughes Medical Institute, Cambridge, MA, USA.

Nature
|March 29, 2023
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Summary
This summary is machine-generated.

Extracellular contractile injection systems (eCISs) can be engineered to deliver proteins into human cells. This breakthrough enables new possibilities for therapeutic protein delivery and gene editing applications.

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Biotechnology

Background:

  • Endosymbiotic bacteria utilize complex delivery systems to interact with host cells.
  • Extracellular contractile injection systems (eCISs) are macromolecular machines that inject protein payloads into eukaryotic cells.
  • Previous studies indicated eCISs target mouse cells, suggesting potential for therapeutic applications.

Purpose of the Study:

  • To investigate the target recognition mechanism of the Photorhabdus virulence cassette (PVC) eCIS.
  • To determine if PVC eCIS can be engineered to target human cells.
  • To assess the capacity of PVC eCIS for delivering diverse protein payloads into human cells.

Main Methods:

  • In silico structure-guided engineering of the PVC tail fiber.
  • Testing PVC eCIS targeting and protein delivery in human cells.
  • Analysis of protein payload delivery, including Cas9 and base editors.

Main Results:

  • Target selection by PVC eCIS is mediated by specific receptor recognition via its tail fiber.
  • PVC eCIS were successfully reprogrammed to target human cells and mice with high efficiency.
  • Diverse protein payloads were functionally delivered into human cells using the engineered PVC system.

Conclusions:

  • PVC eCIS are programmable devices for protein delivery.
  • Engineered PVC systems show potential for applications in gene therapy, cancer therapy, and biocontrol.
  • This study expands the utility of bacterial injection systems for eukaryotic cell manipulation.