Dynamic remodeling of host membranes by self-organizing bacterial effectors

Ting-Sung Hsieh; Victor A Lopez; Miles H Black; Adam Osinski; Krzysztof Pawłowski; Diana R Tomchick; Jen Liou; Vincent S Tagliabracci

doi:10.1126/science.aay8118

Dynamic remodeling of host membranes by self-organizing bacterial effectors

Science. 2021 May 28;372(6545):935-941. doi: 10.1126/science.aay8118. Epub 2021 Apr 29.

Authors

Ting-Sung Hsieh^#¹, Victor A Lopez^#¹, Miles H Black^#¹, Adam Osinski¹, Krzysztof Pawłowski^{1

2}, Diana R Tomchick^{3

4}, Jen Liou⁵, Vincent S Tagliabracci^{6

7

8}

Affiliations

¹ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Department of Biochemistry and Microbiology, Institute of Biology, Warsaw University of Life Sciences, Warsaw 02-776, Poland.
³ Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁴ Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁵ Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁶ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. [email protected].
⁷ Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁸ Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

^# Contributed equally.

Abstract

During infection, intracellular bacterial pathogens translocate a variety of effectors into host cells that modify host membrane trafficking for their benefit. We found a self-organizing system consisting of a bacterial phosphoinositide kinase and its opposing phosphatase that formed spatiotemporal patterns, including traveling waves, to remodel host cellular membranes. The Legionella effector MavQ, a phosphatidylinositol (PI) 3-kinase, was targeted to the endoplasmic reticulum (ER). MavQ and the Legionella PI 3-phosphatase SidP, even in the absence of other bacterial components, drove rapid PI 3-phosphate turnover on the ER and spontaneously formed traveling waves that spread along ER subdomains inducing vesicle and tubule budding. Thus, bacteria can exploit a self-organizing membrane-targeting mechanism to hijack host cellular structures for survival.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Proteins / chemistry
Bacterial Proteins / metabolism*
COS Cells
Chlorocebus aethiops
Endoplasmic Reticulum / metabolism*
Endoplasmic Reticulum / ultrastructure
Feedback, Physiological
HeLa Cells
Host-Pathogen Interactions
Humans
Intracellular Membranes / metabolism*
Intracellular Membranes / ultrastructure
Legionella pneumophila / enzymology
Legionella pneumophila / genetics
Legionella pneumophila / growth & development
Legionella pneumophila / physiology*
Mice
Mutation
Phosphatidylinositol 3-Kinase / chemistry
Phosphatidylinositol 3-Kinase / metabolism*
Phosphatidylinositol Phosphates / chemistry
Phosphatidylinositol Phosphates / metabolism*
Phosphoric Monoester Hydrolases / metabolism
Protein Domains
RAW 264.7 Cells

Substances

Bacterial Proteins
Phosphatidylinositol Phosphates
phosphatidylinositol 3-phosphate
Phosphatidylinositol 3-Kinase
Phosphoric Monoester Hydrolases
phosphatidylinositol-3-phosphatase

Abstract

Publication types

MeSH terms

Substances

Grants and funding