Decision letter: Vibrio deploys type 2 secreted lipase to esterify cholesterol with host fatty acids and mediate cell egress

AbstractPathogens find diverse niches for survival inside host cells where replication occurs in a relatively protected environment. Vibrio parahaemolyticus, a facultative intracellular pathogen, uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. However, after extensive analysis, the T3SS2 pathogenicity island appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of cell biology, microbial genetics and lipid biochemistry, we found that VPA0226, a constitutively secreted lipase, is required for escape of Vibrio parahaemolyticus from host cells. Remarkably, this lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response (i.e. arachidonic acid, 20:4) to esterify cholesterol, weakening the plasma membrane and allowing egress of the bacteria. This study reveals the resourcefulness of microbes and the interplay between virulence systems to evolve an ingenious scheme for survival and escape.Impact StatementConsidering the course of a pathogen’s evolution, there appears to be interplay between secretion systems, providing unique, synergistic mechanisms to support a successful lifestyle for possibly pathogenesis, symbiosis and/or parasitosis.

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Vibrio deploys type 2 secreted lipase to esterify cholesterol with host fatty acids and mediate cell egress

eLife ◽

10.7554/elife.58057 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Suneeta Chimalapati ◽

Marcela de Souza Santos ◽

Alexander E Lafrance ◽

Ann Ray ◽

Wan-Ru Lee ◽

...

Keyword(s):

Fatty Acids ◽

Host Cell ◽

Host Cells ◽

Host Cytoplasm ◽

System 2 ◽

Protective Environment ◽

Mediate Cell ◽

Type 3 ◽

Secreted Lipase ◽

Esterify Cholesterol

Pathogens find diverse niches for survival including inside a host cell where replication occurs in a relatively protective environment. Vibrio parahaemolyticus is a facultative intracellular pathogen that uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. Analysis of the T3SS2 pathogenicity island encoding the T3SS2 appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of molecular tools, we found that VPA0226, a constitutively secreted lipase, is required for escape of V. parahaemolyticus from the host cells. This lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response to esterify cholesterol, weakening the plasma membrane and allowing egress of the bacteria. This study reveals the resourcefulness of microbes and the interplay between virulence systems and host cell resources to evolve an ingenious scheme for survival and escape.

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The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre

Acta Diabetologica ◽

10.1007/s00592-021-01727-5 ◽

2021 ◽

Author(s):

Dominic Salamone ◽

Angela Albarosa Rivellese ◽

Claudia Vetrani

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Gut Microbiota ◽

Dietary Fibre ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Microbiota Composition ◽

The Relationship ◽

Chain Fatty Acids

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.

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Interaction between Erythrocyte Phospholipid Fatty Acids Composition and Variants of Inflammation-Related Genes on Type 2 Diabetes

Journal of Nutrigenetics and Nutrigenomics ◽

10.1159/000381347 ◽

2015 ◽

Vol 7 (4-6) ◽

pp. 252-263 ◽

Cited By ~ 3

Author(s):

Kelei Li ◽

Tao Huang ◽

Ju-Sheng Zheng ◽

Jianqin Sun ◽

Yanqiu Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Phospholipid Fatty Acids ◽

Fatty Acids Composition

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Plasma concentrations of trans fatty acids in persons with type 2 diabetes between September 2002 and April 2004

American Journal of Clinical Nutrition ◽

10.3945/ajcn.112.046508 ◽

2013 ◽

Vol 97 (4) ◽

pp. 862-871 ◽

Cited By ~ 9

Author(s):

Dawn C Schwenke ◽

John P Foreyt ◽

Edgar R Miller ◽

Rebecca S Reeves ◽

Mara Z Vitolins ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Trans Fatty Acids ◽

Plasma Concentrations

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Evidence for a novel pathway for the targeting of a Saccharomyces cerevisiae peroxisomal protein belonging to the isomerase/hydratase family

Journal of Cell Science ◽

10.1242/jcs.113.3.533 ◽

2000 ◽

Vol 113 (3) ◽

pp. 533-544

Author(s):

I.V. Karpichev ◽

G.M. Small

Keyword(s):

Saccharomyces Cerevisiae ◽

Fatty Acids ◽

Unsaturated Fatty Acids ◽

Beta Oxidation ◽

Peroxisomal Protein ◽

Intracellular Targeting ◽

Targeting Signals ◽

Peroxisome Targeting Signals

We, and others, have identified a novel Saccharomyces cerevisiae peroxisomal protein that belongs to the isomerase/hydratase family. The protein, named Dci1p, shares 50% identity with Eci1p, a delta(3)-cis-delta(2)-trans-enoyl-CoA isomerase that acts as an auxiliary enzyme in the beta-oxidation of unsaturated fatty acids. Both of these proteins are localized to peroxisomes, and both contain motifs at their amino- and carboxyl termini that resemble peroxisome targeting signals (PTS) 1 and 2. However, we demonstrate that the putative type 1 signaling motif is not required for the peroxisomal localization of either of these proteins. Furthermore, the correct targeting of Eci1p and Dci1p occurs in the absence of the receptors for the type 1 or type 2 peroxisome targeting pathway. Together, these data suggest a novel mechanism for the intracellular targeting of these peroxisomal proteins.

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