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Related Experiment Videos

Redefining the essential trafficking pathway for outer membrane lipoproteins.

Marcin Grabowicz1, Thomas J Silhavy2

  • 1Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

Proceedings of the National Academy of Sciences of the United States of America
|April 19, 2017
PubMed
Summary

Gram-negative bacteria outer membrane (OM) lipoprotein trafficking is essential, but LolA and LolB are not strictly required. The Cpx stress response bypasses these proteins, preventing lethal mislocalization.

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Area of Science:

  • Microbiology
  • Bacterial Cell Envelope
  • Protein Trafficking

Background:

  • The Gram-negative bacterial outer membrane (OM) is a critical permeability barrier and antibiotic resistance factor.
  • Lipoproteins are essential components of the OM, involved in various cellular processes including cell wall synthesis and antibiotic efflux.
  • The periplasmic chaperone LolA and OM receptor LolB are believed to be essential for trafficking lipoproteins to the OM.

Purpose of the Study:

  • To investigate the essentiality of LolA and LolB in lipoprotein trafficking to the Gram-negative bacterial outer membrane.
  • To identify the mechanisms that regulate lipoprotein trafficking and the bacterial response to mislocalized lipoproteins.

Main Methods:

  • Genetic manipulation of bacterial strains to bypass LolA and LolB functions.
Keywords:
Cpx responseLol pathwayNlpElipoprotein traffickingouter membrane

Related Experiment Videos

  • Activation of the envelope stress response.
  • Assessment of lipoprotein trafficking and cell viability.

    • Main Results:

    • LolA and LolB can be bypassed by activating the Cpx envelope stress response, even without toxic mislocalized substrates.
    • The Cpx stress response monitors lipoprotein trafficking and protects the cell from mislocalized lipoproteins.
    • An alternative trafficking pathway exists, indicating LolA and LolB are not mechanistically essential for trafficking itself.

    Conclusions:

    • The essentiality of LolA and LolB is primarily linked to preventing lethal accumulation of mislocalized lipoproteins, not essential mechanistic steps in trafficking.
    • The Cpx stress response plays a crucial role in managing lipoprotein trafficking and cellular integrity.
    • Gram-negative bacteria possess alternative pathways for lipoprotein transport under specific stress conditions.