Research Article

Dynamic remodeling of host membranes by self-organizing bacterial effectors

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Science  28 May 2021:
Vol. 372, Issue 6545, pp. 935-941
DOI: 10.1126/science.aay8118

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Bacterial effectors manipulate membranes

Many pathogenic bacteria use molecular syringes to translocate proteins called effectors into the host cell to hijack the cellular machinery for their proliferation. Legionella pneumophila, the causative bacteria of Legionnaires' disease, uses a large effector arsenal and harnesses the host membrane system to establish a specialized vacuole where it replicates. Hsieh et al. show that, within this effector arsenal, the phospholipid kinase MavQ and the phosphatase SidP work together and self-organize on the intracellular membrane network of its eukaryotic host to promote membrane remodeling. The interactions between MavQ and SidP constitute positive and negative feedback loops, respectively, that orchestrate their spatiotemporal oscillation during infection.

Science, aay8118, this issue p. 935


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.

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