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Microtubule motors control membrane dynamics of Salmonella-containing vacuoles

Julie Guignot1, Emmanuelle Caron, Carmen Beuzón

  • 1Department of Infectious Diseases, Centre for Molecular Microbiology and Infection, Imperial College London, London, SW7 2AZ, UK.

Journal of Cell Science
|February 19, 2004
PubMed

Insights

Salmonella Typhimurium infection hijacks host cell microtubules. Microtubule motors are crucial for Salmonella-containing vacuole (SCV) integrity and bacterial replication within host cells.

Area of Science:

  • Cell Biology
  • Microbiology
  • Infectious Diseases

Background:

  • Salmonella enterica serovar Typhimurium (S. typhimurium) invades host cells, residing within Salmonella-containing vacuoles (SCVs).
  • SCVs are specialized compartments essential for bacterial survival and replication.
  • S. typhimurium utilizes effector proteins, like SifA, translocated via the SPI-2 type III secretion system, to manipulate host cell processes and maintain SCV integrity.

Purpose of the Study:

  • To investigate the role of host cell microtubules and motor proteins in the intracellular lifestyle of S. typhimurium.
  • To elucidate the mechanisms by which S. typhimurium manipulates microtubule dynamics around SCVs.
  • To understand the contribution of microtubule motors to SCV dynamics and bacterial replication.

Main Methods:

  • Microscopy to observe SCV and microtubule organization in infected epithelial cells and macrophages.
  • Inhibition of kinesin and dynein motor activity.
  • Analysis of Sif formation, vacuolar membrane integrity, and bacterial replication.
  • Investigation of the role of Rab7 and its effector RILP in dynein recruitment to SCVs.

Main Results:

  • Intracellular S. typhimurium induces significant microtubule accumulation around bacterial microcolonies, independent of SPI-2 actin assembly but dependent on bacterial protein synthesis.
  • Microtubule motor proteins, kinesin and dynein, are recruited to SCVs in epithelial cells.
  • Inhibition of kinesin or dynein impairs Sif formation, leads to vacuolar membrane loss in sifA mutants, causes abnormal vacuole morphology, and reduces wild-type bacterial replication.
  • Dynein recruitment to SCVs is dependent on Rab7 activity, and while RILP is recruited in a Rab7-dependent manner, it may not be the sole mediator of dynein recruitment.

Conclusions:

  • Microtubule motors play a critical role in regulating vacuolar membrane dynamics during intracellular S. typhimurium replication.
  • The recruitment and activity of microtubule motors are essential for maintaining SCV integrity and promoting bacterial proliferation.
  • Rab7 and its effectors are involved in the recruitment of dynein to SCVs, highlighting a complex interplay between host cell machinery and bacterial pathogens.

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