Subversion of the Endocytic and Secretory Pathways by Bacterial Effector Proteins

Weber, Mary M.; Faris, Robert

doi:10.3389/fcell.2018.00001

Cited by 98 publications

(87 citation statements)

References 147 publications

(203 reference statements)

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“…41 In general, secreted bacterial virulence factors are known for their capacity to produce cellular changes that subvert host cell endocytic and secretory pathway functions. 42 Such cellular changes are commonly observed as a result of infection by obligate and facultative intracellular pathogens, with some pathogens and virulence factors inducing changes in the distribution of intracellular components of polarized intestinal epithelial cells. For example, Shiga toxin disrupts retrograde vesicle trafficking 43 to incite epithelial cell intoxication.…”

Section: Implications For Vibrio Cholerae Pathophysiologymentioning

confidence: 99%

Cholix protein domain I functions as a carrier element for efficient apical to basal epithelial transcytosis

et al. 2020

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Cholix (Chx) is expressed by the intestinal pathogen Vibrio cholerae as a single chain of 634 amino acids (~70.7 kDa protein) that folds into three distinct domains, with elements of the second and third domains being involved in accessing the cytoplasm of nonpolarized cells and inciting cell death via ADP-ribosylation of elongation factor 2, respectively. In order to reach nonpolarized cells within the intestinal lamina propria, however, Chx must cross the polarized epithelial barrier in an intact form. Here, we provide in vitro and in vivo demonstrations that a nontoxic Chx transports across intestinal epithelium via a vesicular trafficking pathway that rapidly achieves vesicular apical to basal (A→B) transcytosis and avoids routing to lysosomes. Specifically, Chx traffics in apical endocytic Rab7 + vesicles and in basal exocytic Rab11 + vesicles with a transition between these domains occurring in the ER-Golgi intermediate compartment (ERGIC) through interactions with the lectin mannose-binding protein 1 (LMAN1) protein that undergoes an intracellular redistribution that coincides with the reorganization of COPI + and COPII + vesicular structures. Truncation studies demonstrated that domain I of Chx alone was sufficient to efficiently complete A→B transcytosis and capable of ferrying genetically conjoined human growth hormone (hGH). These studies provide evidence for a pathophysiological strategy where native Chx exotoxin secreted in the intestinal lumen by nonpandemic V. cholerae can reach nonpolarized cells within the lamina propria in an intact form by using a nondestructive pathway to cross in the intestinal epithelial that appears useful for oral delivery of biopharmaceuticals. One-Sentence Summary: Elements within the first domain of the Cholix exotoxin protein are essential and sufficient for the apical to basal transcytosis of this Vibrio cholerae-derived virulence factor across polarized intestinal epithelial cells.

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Section: Implications For Vibrio Cholerae Pathophysiologymentioning

confidence: 99%

Cholix protein domain I functions as a carrier element for efficient apical to basal epithelial transcytosis

et al. 2020

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“…Many microbial pathogens exploit, disrupt, or otherwise modulate host membrane trafficking pathways in order to establish infection (Weber & Faris, ). This review focuses on interaction of pathogens with a host trafficking event termed “exocytosis,” the fusion of intracellular vesicles with the plasma membrane (Rizo & Sudhof, ; Taguchi, ; Wu & Guo, ).…”

Section: Introductionmentioning

confidence: 99%

Interaction of microbial pathogens with host exocytic pathways

Ireton

Ngo

Bhalla

2018

Cellular Microbiology

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Many microbial pathogens co-opt or perturb host membrane trafficking pathways. This review covers recent examples in which microbes interact with host exocytosis, the fusion of intracellular vesicles with the plasma membrane. The bacterial pathogens Listeria monocytogenes and Staphylococcus aureus subvert recycling endosomal pathways of exocytosis in order to induce their entry into human cells. By contrast, entry of the protozoan pathogen Trypanosoma cruzi or the virus adenovirus into host cells involves exploitation of lysosomal exocytosis. Toxins produced by Bacillus anthracis or Vibrio cholerae interfere with exocytosis pathways mediated by the GTPase Rab11 and the exocyst complex. By doing so, anthrax or cholera toxins impair recycling of cadherins to cell-cell junctions and disrupt the barrier properties of endothelial cells or intestinal epithelial cells, respectively. Uropathogenic Escherichia coli (UPEC) is expelled from bladder epithelial cells through two different exocytic routes that involve sensing of bacteria in vacuoles by host Toll-like receptor 4 (TLR4) or monitoring of the pH of lysosomes harbouring UPEC. The TLR4 pathway is mediated by multiple Rab GTPases and the exocyst, whereas the other pathway involves exocytosis of lysosomes. Expulsion of UPEC through these pathways is thought to benefit the host.

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“…The different membrane-bound organelles that compose the secretory pathway and the endo-lysosomal system of eukaryotic cells constitute targets of choice for many intracellular pathogens, which have evolved highly diverse strategies to hijack and/or subvert these trafficking pathways to their benefit (2, 3). In that context, the importance of retrograde trafficking for the infection cycle of a number of human pathogens (viruses and bacteria) has been recognized in the past years (e.g., (42, 43)).…”

Section: Discussionmentioning

confidence: 99%

“…Cellular invasion is a common strategy shared by many bacterial pathogens of human and animals in order to escape host defenses and to establish a protected replicative niche. This notably applies to the human pathogens of the genus Salmonella , Shigella , Legionella , or Brucella (1–3). Knowledge of the host cellular pathways that are subverted by these pathogenic bacteria in order to reach and/or establish their intracellular replicative niches can be highly instructive for the development of new treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

A role for the VPS retromer inBrucellaintracellular replication revealed by genome-wide siRNA screening

Casanova

Low

Québatte

et al. 2018

Preprint

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26Brucella, the causing agent of brucellosis, is a major zoonotic pathogen with worldwide 27 distribution. Brucella resides and replicates inside infected host cells in membrane-bound 28 compartments called BCVs (Brucella-containing vacuoles). Following uptake, Brucella 29 resides in eBCVs (endosomal BCVs) that gradually mature from early to late endosomal 30 features. Through a poorly understood process that is key to the intracellular lifestyle of 31 Brucella, the eBCV escapes fusion with lysosomes by transitioning to the rBCV (replicative 32 BCV), a replicative niche directly connected to the endoplasmic reticulum (ER). Despite the 33 notion that this complex intracellular lifestyle must depend on a multitude of host factors, a 34 holistic view on which of these components control Brucella cell entry, trafficking and 35 replication is still missing. Here we used a systematic cell-based siRNA knockdown screen in 36HeLa cells infected with Brucella abortus and identified 425 components of the human 37 infectome for Brucella infection. These include multiple components of pathways involved in 38 central processes such as cell cycle, actin cytoskeleton dynamics or vesicular trafficking. Using 39 assays for pathogen entry, knockdown complementation and co-localization at single-cell 40 resolution, we identified the requirement of the VPS retromer for Brucella to escape the 41 lysosomal degradative pathway and to establish its intracellular replicative niche. We thus 42 validated a component of the VPS retromer as novel host factor critical for Brucella 43 intracellular trafficking. Further, our genome-wide data shed light on the interplay between 44 central host processes and the biogenesis of the Brucella replicative niche. 45 46 3 Importance 47With >300,000 new cases of human brucellosis annually, Brucella is regarded as one of the 48 most important zoonotic bacterial pathogen worldwide. The causing agent of brucellosis 49 resides inside host cells within vacuoles termed Brucella containing vacuoles (BCVs). 50Although few host components required to escape the degradative lysosomal pathway and to 51 establish the ER-derived replicative BCV (rBCV) have already been identified, the global 52 understanding of this highly coordinated process is still partial and many factors remain 53 unknown. To gain a deeper insight into these fundamental questions we performed a genome-54 wide RNA interference (RNAi) screen aiming at discovering novel host factors involved in the 55Brucella intracellular cycle. We identified 425 host proteins that contribute to Brucella cellular 56 entry, intracellular trafficking, and replication. Together, this study sheds light on previously 57 unknown host pathways required for the Brucella infection cycle and highlights the VPS 58 retromer components as critical factors for the establishment of the Brucella intracellular 59 replicative niche. 60 61 62Cellular invasion is a common strategy shared by many bacterial pathogens of human and 63 animals in order to escape host defenses and to establ...

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Subversion of the Endocytic and Secretory Pathways by Bacterial Effector Proteins

Cited by 98 publications

References 147 publications

Cholix protein domain I functions as a carrier element for efficient apical to basal epithelial transcytosis

Cholix protein domain I functions as a carrier element for efficient apical to basal epithelial transcytosis

Interaction of microbial pathogens with host exocytic pathways

A role for the VPS retromer inBrucellaintracellular replication revealed by genome-wide siRNA screening

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