The Vibrio parahaemolyticus effector VopQ induces autophagosome accumulation in host cells

Abstract

Vibrio parahaemolyticus, a Gram‐negative bacterium, is the leading cause of seafood‐borne illness in the United States. This pathogen is able to infect and survive in humans by manipulating the host cellular machinery via bacterial Type III effector proteins that are translocated into the host cell, where they disrupt cellular signaling. One of the principal effector proteins, VopQ, has been demonstrated to be necessary and sufficient to induce autophagosome accumulation. I propose to elucidate the precise cellular and molecular mechanism by which VopQ induces autophagosome accumulation. Since autophagosomes are transient vesicles, the accumulation could be due to an increase in formation of autophagosomes or a decrease in lysosomal fusion. Using biochemical assays and yeast genetics we have uncovered a novel target that reveals the role of VopQ in vesicle fusion during autophagy.With the discovery of several bacterial effectors that function to manipulate host membranes, many eukaryotic vesicle trafficking pathways have been unveiled, and many new questions have surfaced about the mechanisms of novel bacterial effectors. Understanding the mechanism by which VopQ induces autophagosome accumulation could be essential in understanding V. para infection and could give new insights into the mechanisms of eukaryotic vesicle trafficking.

Chromogranin B (CHGB) is dimorphic and responsible for dominant anion channels delivered to cell surface via regulated secretion

“…For example, C-type lectins released from small intestine epithelial cells reconstitute hexameric pores in membranes of G + bacteria to kill the germs (Mukherjee et al, 2009(Mukherjee et al, , 2014. VopQ, a pathogenic effector protein of the Vibrio species, is released inside infected cells to puncture lysosomal or vacuolar membranes by forming non-selective channels, which then causes cell demise (Sreelatha et al, 2013(Sreelatha et al, , 2015. Other examples include non-selective CLIC proteins (Tulk et al, 2000;Ashley, 2003;Edwards, 2010;Gururaja Rao et al, 2017;Hossain et al, 2019), membrane-attacking C5b/C6-9 complexes (Michaels et al, 1976;Young and Young, 1990;Zalman and Muller-Eberhard, 1990;Bayly-Jones et al, 2017;Menny et al, 2018;Parsons et al, 2019), colicins (Schein et al, 1978;Weaver et al, 1981;Kienker et al, 2000), Gasdermin D N-terminal domains (GSDMD) in pyroptosis (Chen et al, 2016;Ding et al, 2016;Liu et al, 2016;Ruhl and Broz, 2016;Ruan et al, 2018), BAK or BAX in mitochondria (Antignani and Youle, 2006;Cosentino and Garcia-Saez, 2017;Uren et al, 2017a,b), phosphorylated MLKL channels for necroptosis (Su et al, 2014;Wang et al, 2014;Zhang and Han, 2016;Shrestha et al, 2019), microbiocidal defensins (Hristova et al, 1996;Zhang et al, 2010;Awang and Pongprayoon, 2018), etc.…”