Abstract

The type IV secretion system (T4SS) VirB/D4 of the facultative intracellular pathogen Bartonella henselae is known to translocate bacterial effector proteins into human cells. Two recent reports on DNA transfer into human cells have demonstrated the versatility of this bacterial secretion system for macromolecular substrate transfer. Moreover, these findings have opened the possibility for developing new tools for DNA delivery into specific human cell types. DNA can be introduced into these cells covalently attached to a site-specific integrase with potential target sequences in the human genome. This novel DNA delivery system is discussed in the context of existing methods for genetic modification of human cells.

Highlights

  • Bartonella henselae is known to translocate bacterial effector proteins into human cells

  • Of bacterial pathogens constitutes an additional example of the surprising versatility of these secretion systems, and it provides the foundation for new DNA delivery tools with exciting possibilities

  • Different T4SS-containing pathogens could be used to secrete a nucleoprotein complex accompanied by helper proteins, consisting of the DNA of choice covalently linked to a protein with integrase activity, directly into the cytoplasm of their target human cells

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Summary

Introduction

Bartonella henselae is known to translocate bacterial effector proteins into human cells. Some of the described problems for conventional gene delivery methods may be overcome by a recently reported means to deliver DNA into human cells that exploits a T4SS of the facultative intracellular human pathogen Bartonella henselae 18, to be secreted, since both protein and DNA molecules are transferred. . Bacterial T4SS show a remarkable plasticity in terms of the nature of the substrate conjugation 21, or effector protein translocation into human cells 22.

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