A Vibrio effector protein is an inositol phosphatase and disrupts host cell membrane integrity.
The marine bacterium Vibrio parahaemolyticus causes gastroenteritis in humans and encodes the type III effector protein VPA0450, which contributes to host cell death caused by autophagy, cell rounding, and cell lysis. We found that VPA0450 is an inositol polyphosphate 5-phosphatase that hydrolyzed the D5 phosphate from the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate. VPA0450 disrupted cytoskeletal binding sites on the inner surface of membranes of human cells and caused plasma membrane blebbing, which compromised membrane integrity and probably contributed to cell death by facilitating lysis. Thus, bacterial pathogens can disrupt adaptor protein-binding sites required for proper membrane and cytoskeleton dynamics by altering the homeostasis of membrane-bound inositol-signaling molecules.
Broberg
Christopher A
CA
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Zhang
Lingling
L
Gonzalez
Herman
H
Laskowski-Arce
Michelle A
MA
Orth
Kim
K
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D001343:Autophagy; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D048430:Cell Shape; D019295:Computational Biology; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D014162:Transfection; D014736:Vibrio parahaemolyticus / Q000201:enzymology* / Q000472:pathogenicity*
D000199:Actins; D001426:Bacterial Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; C553203:VPA0450 protein, Vibrio parahaemolyticus; C021822:myo-inositol-1 (or 4)-monophosphatase; D000072181:Inositol Polyphosphate 5-Phosphatases