The role of lipid droplets in microbial pathogenesis

Brink, Jacobus T R; Fourie, Ruan; Sebolai, Olihile M.; Albertyn, Jacobus; Pohl, Carolina H.

doi:10.1099/jmm.0.001383

Cited by 14 publications

(9 citation statements)

References 166 publications

(316 reference statements)

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“…The formation of viroplasms requires host lipid droplets (LDs) and several viral proteins, specifically NSP2 and NSP5 (Cheung et al, 2010;Kim et al, 2012;Gaunt et al, 2013;Crawford and Desselberger, 2016). Lipid droplets are organelles that play diverse roles in the physiology and pathophysiology of cells (Walther et al, 2017;Brink et al, 2021). The major components, making up the neutral core of LDs, are triacylglycerols and sterol esters, which serve as energy stores during nutrient deprivation (Jackson et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Rotavirus-Mediated Prostaglandin E2 Production in MA104 Cells Promotes Virus Attachment and Internalisation, Resulting in an Increased Viral Load

et al. 2022

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Rotaviruses are one of the leading causes of severe dehydrating diarrhoea in infants and children under the age of five. Despite the introduction of vaccines, disease burden remains high in sub-Saharan Africa, with no known anti-viral treatments available. During early infection rotavirus attaches to several cellular receptors and enters the cells by either clathrin-dependent or -independent endocytosis. Prostaglandin E2, an abundant eicosanoid, is produced from arachidonic acid during rotavirus infection and inhibition of prostaglandin E2 formation have a deleterious effect on rotavirus infection. In this study, MA104 cells were supplemented with γ-linolenic acid (GLA), a precursor of arachidonic acid. Infection of supplemented cells with rotavirus SA11 led to a depletion in the relative percentages of GLA and arachidonic acid which coincided with an increased production of prostaglandin E2 as monitored by ELISA. Confocal microscopy demonstrated that prostaglandin E2 co-localises with the viroplasm-forming proteins, NSP5 and NSP2. Due to the known association of viroplasms with lipid droplets and the fact that lipid droplets are sites for prostaglandin E2 production, our results indicate a possible role for viroplasms in the production of rotavirus-induced prostaglandin E2. Replication kinetics showed that inhibitors, targeting the biosynthesis of prostaglandin E2, had negative effects on rotavirus yield, especially during the early stages of infection. Using flow cytometry and prostaglandin E2 addback experiments, we show that prostaglandin E2 enhances the attachment and internalisation of rotavirus in MA104 cells indicating a possible role for prostaglandin E2 during clathrin-mediated rotavirus entry. The production of prostaglandin E2 during rotavirus infection could serve as a possible target for anti-viral treatment.

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Section: Introductionmentioning

confidence: 99%

Rotavirus-Mediated Prostaglandin E2 Production in MA104 Cells Promotes Virus Attachment and Internalisation, Resulting in an Increased Viral Load

et al. 2022

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“…In addition to L. pneumophila , several intracellular pathogens accumulate LDs on their pathogen vacuoles to get access to and metabolize fatty acids (Walpole et al, 2018; Bosch et al, 2021; Brink et al, 2021). Pathogenic Mycobacterium species, such as M. tuberculosis and M. leprae , trigger LD formation during infection, to exploit lipids derived from these organelles as carbon and energy source.…”

Section: Discussionmentioning

confidence: 99%

The large GTPase Sey1/atlastin mediates lipid droplet- and FadL-dependent intracellular fatty acid metabolism ofLegionella pneumophila

Hüsler

Stauffer

Keller

et al. 2022

Preprint

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The facultative intracellular bacterium Legionella pneumophila employs the Icm/Dot type IV secretion system (T4SS) to replicate in a unique membrane-bound compartment, the Legionella containing vacuole (LCV). The endoplasmic reticulum (ER)-resident large fusion GTPase Sey1/atlastin promotes remodeling and expansion of LCVs, and the GTPase is also implicated in the formation of ER-derived lipid droplets (LDs). Here we show that LCVs intimately interact with palmitate-induced LDs in Dictyostelium discoideum amoeba. Comparative proteomics of LDs isolated from the D. discoideum parental strain Ax3 or Δsey1 revealed 144 differentially produced proteins, of which 7 or 22 were exclusively detected in LDs isolated from strain Ax3 or Δsey1, respectively. Using dually fluorescence-labeled amoeba producing the LCV marker P4C GFP or AmtA-GFP and the LD marker mCherry-perilipin, we discovered that Sey1 and the L. pneumophila Icm/Dot T4SS as well as the effector LegG1 promote LCV-LD interactions. In vitro reconstitution of the LCV-LD interactions using purified LCVs and LDs from D. discoideum Ax3 or Δsey1 revealed that Sey1 and GTP promote this process. The LCV-LD interactions were impaired for Δsey1-derived LDs, suggesting that Sey1 regulates LD composition. Palmitate promoted the growth of (i) L. pneumophila wild-type in D. discoideum Ax3 but not in Δsey1 mutant amoeba and (ii) L. pneumophila wild-type but not ΔfadL mutant bacteria lacking a homologue of the E. coli fatty acid transporter FadL. Finally, isotopologue profiling indicated that intracellular L. pneumophila metabolizes 13C-palmitate, and its catabolism was reduced in D. discoideum Δsey1 and L. pneumophila ΔfadL. Taken together, our results reveal that Sey1 mediates LD- and FadL-dependent fatty acid metabolism of intracellular L. pneumophila.

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“…Likewise, intracellular protozoan parasites such as Trypanosoma cruzi or Leishmania major associate with LDs to acquire host lipids (D'Avila et al, 2011; Rabhi et al, 2012). Excellent reviews have been published on the role of LDs for interactions of host cells with viruses, bacteria, fungi, and parasites (Barisch & Soldati, 2017a; Brink et al, 2021; Herker et al, 2021; Libbing et al, 2019; Roingeard & Melo, 2017; Vallochi et al, 2018). In the following chapters, we will outline recent discoveries elucidating the role of LDs for selected bacteria–host cell interactions.…”

Section: Subversion Of Lipid Droplets By Microbial Pathogensmentioning

confidence: 99%

“…Due to their many functions, LDs have become the focus of intensive research. In the course of the last decade, there have been multiple excellent reviews extensively discussing the topics of LD homeostasis (Cohen, 2018; Hashemi & Goodman, 2015; Henne et al, 2018), function (Welte & Gould, 2017), motility (Kilwein & Welte, 2019), and organelle interactions (Olzmann & Carvalho, 2019; Rakotonirina‐Ricquebourg et al, 2022), as well as LD‐dependent cellular signaling and innate immunity (Bosch et al, 2021; Bosch & Pol, 2022), and the role of LDs for host–pathogen interactions (Brink et al, 2021; Herker et al, 2021; Libbing et al, 2019; Welte, 2015). This review will summarize the current state of knowledge regarding the biogenesis and functions of LDs, and then focus on the modulation of lipids and LDs in the context of intracellular lipid and FA metabolism by selected pathogenic bacteria.…”

Section: Introductionmentioning

confidence: 99%

Tapping lipid droplets: A rich fat diet of intracellular bacterial pathogens

Hüsler

Stauffer

Hilbi

2023

Molecular Microbiology

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Lipid droplets (LDs) are dynamic and versatile organelles present in most eukaryotic cells. LDs consist of a hydrophobic core of neutral lipids, a phospholipid monolayer coat, and a variety of associated proteins. LDs are formed at the endoplasmic reticulum and have diverse roles in lipid storage, energy metabolism, membrane trafficking, and cellular signaling. In addition to their physiological cellular functions, LDs have been implicated in the pathogenesis of several diseases, including metabolic disorders, cancer, and infections. A number of intracellular bacterial pathogens modulate and/or interact with LDs during host cell infection. Members of the genera Mycobacterium, Legionella, Coxiella, Chlamydia, and Salmonella exploit LDs as a source of intracellular nutrients and membrane components to establish their distinct intracellular replicative niches. In this review, we focus on the biogenesis, interactions, and functions of LDs, as well as on their role in lipid metabolism of intracellular bacterial pathogens.

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The role of lipid droplets in microbial pathogenesis

Cited by 14 publications

References 166 publications

Rotavirus-Mediated Prostaglandin E2 Production in MA104 Cells Promotes Virus Attachment and Internalisation, Resulting in an Increased Viral Load

Rotavirus-Mediated Prostaglandin E2 Production in MA104 Cells Promotes Virus Attachment and Internalisation, Resulting in an Increased Viral Load

The large GTPase Sey1/atlastin mediates lipid droplet- and FadL-dependent intracellular fatty acid metabolism ofLegionella pneumophila

Tapping lipid droplets: A rich fat diet of intracellular bacterial pathogens

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