Host but Not Parasite Cholesterol ControlsToxoplasmaCell Entry by Modulating Organelle Discharge

Host cell cholesterol is implicated in the entry and replication of an increasing number of intracellular microbial pathogens. Although uptake of viral particles via cholesterol-enriched caveolae is increasingly well described, the requirement of cholesterol for internalization of eukaryotic pathogens is poorly understood and is likely to be partly organism specific. We examined the role of cholesterol in active host cell invasion by the protozoan parasite Toxoplasma gondii. The parasitophorous vacuole membrane (PVM) surrounding T. gondii contains cholesterol at the time of invasion. Although cholesterol-enriched parasite apical organelles termed rhoptries discharge at the time of cell entry and contribute to PVM formation, surprisingly, rhoptry cholesterol is not necessary for this process. In contrast, host plasma membrane cholesterol is incorporated into the forming PVM during invasion, through a caveolae-independent mechanism. Unexpectedly, depleting host cell plasma membrane cholesterol blocks parasite internalization by reducing the release of rhoptry proteins that are necessary for invasion. Cholesterol back-addition into host plasma membrane reverses this inhibitory effect of depletion on parasite secretion. These data define a new mechanism by which host cholesterol specifically controls entry of an intracellular pathogen.

Download Full-text

Toxoplasma invasion: the parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.93.16.8413 ◽

1996 ◽

Vol 93 (16) ◽

pp. 8413-8418 ◽

Cited By ~ 189

Author(s):

E. Suss-Toby ◽

J. Zimmerberg ◽

G. E. Ward

Keyword(s):

Plasma Membrane ◽

Host Cell ◽

Parasitophorous Vacuole ◽

Cell Plasma Membrane ◽

Cell Plasma

Download Full-text

The Nascent Parasitophorous Vacuole Membrane of Encephalitozoon cuniculi Is Formed by Host Cell Lipids and Contains Pores Which Allow Nutrient Uptake

Eukaryotic Cell ◽

10.1128/ec.00004-08 ◽

2008 ◽

Vol 7 (6) ◽

pp. 1001-1008 ◽

Cited By ~ 29

Author(s):

Karin Rönnebäumer ◽

Uwe Gross ◽

Wolfgang Bohne

Keyword(s):

Plasma Membrane ◽

Host Cell ◽

Fluorescent Dyes ◽

Parasitophorous Vacuole ◽

Time Lapse ◽

Host Cells ◽

Encephalitozoon Cuniculi ◽

Invasion Mechanism ◽

Cell Plasma ◽

Metabolite Exchange

ABSTRACT Microsporidia are obligate intracellular pathogens which enter host cells by the discharge of a hollow tube through which the sporoplasma is extruded into the host cell. Since this invasion mechanism is very different from common entry strategies, the formation of the parasitophorous vacuole (PV) in Encephalitozoon species is likely to be distinct from known principles. We investigated the origin of the nascent Encephalitozoon cuniculi PV membrane with the aid of fluorescent lipid probes. When Bodipy 500/510-C12-HPC-labeled spores were used for infection, the emerging PV membrane was unlabeled, suggesting that sporoplasma-derived lipids do not significantly contribute to the formation of the PV membrane. In contrast, when raft and nonraft microdomains of the host cell plasma membrane were selectively labeled with DiIC16 and Speedy DiO, both tracers were detectable in the nascent PV membrane shortly after infection, indicating that the bulk lipids of the PV membrane are host cell derived. Time-lapse fluorescence microscopy revealed that the formation of the PV membrane is a fast event (<1.3 s), which occurred simultaneously with the extrusion of the sporoplasma. The portion of the discharged tube which is in contact with the host cell was found to be coated with labeled host cell lipids, which might be an indication for a plasma membrane invagination at the contact site. To investigate the presence of pores in the E. cuniculi PV membrane, we microinjected fluorescent dyes of different sizes into infected host cells. A 0.5-kDa dextran as well as 0.8- to 1.1-kDa peptides could rapidly enter the PV, while a 10-kDa dextran was stably excluded from the PV lumen, indicating that the PV membrane possesses pores with an exclusion size of <10 kDa, which should allow metabolite exchange.

Download Full-text

Cell plasma membrane cholesterol as a diagnostic

Current Opinion in Electrochemistry ◽

10.1016/j.coelec.2017.04.004 ◽

2017 ◽

Vol 2 (1) ◽

pp. 82-87 ◽

Cited By ~ 3

Author(s):

Li Li ◽

Binyu Lu ◽

Dechen Jiang ◽

Minchul Shin ◽

Thomas J. Kelley ◽

...

Keyword(s):

Plasma Membrane ◽

Membrane Cholesterol ◽

Cell Plasma Membrane ◽

Cell Plasma ◽

Plasma Membrane Cholesterol

Download Full-text

Sterols, Oxysterols, and Accessible Cholesterol: Signalling for Homeostasis, in Immunity and During Development

Frontiers in Physiology ◽

10.3389/fphys.2021.723224 ◽

2021 ◽

Vol 12 ◽

Author(s):

William J. Griffiths ◽

Yuqin Wang

Keyword(s):

Plasma Membrane ◽

Total Cell ◽

Cholesterol Homeostasis ◽

Microbial Pathogens ◽

Membrane Cholesterol ◽

Hedgehog Signalling ◽

Signalling Molecule ◽

Hedgehog Signalling Pathway ◽

Patched 1 ◽

Plasma Membrane Cholesterol

In this article we discuss the concept of accessible plasma membrane cholesterol and its involvement as a signalling molecule. Changes in plasma membrane accessible cholesterol, although only being minor in the context of total cholesterol plasma membrane cholesterol and total cell cholesterol, are a key regulator of overall cellular cholesterol homeostasis by the SREBP pathway. Accessible cholesterol also provides the second messenger between patched 1 and smoothened in the hedgehog signalling pathway important during development, and its depletion may provide a mechanism of resistance to microbial pathogens including SARS-CoV-2. We revise the hypothesis that oxysterols are a signalling form of cholesterol, in this instance as a rapidly acting and paracrine version of accessible cholesterol.

Download Full-text

Microelectrode Analysis of Cell Plasma Membrane Cholesterol

ECS Meeting Abstracts ◽

10.1149/ma2014-01/22/992 ◽

2014 ◽

Keyword(s):

Plasma Membrane ◽

Membrane Cholesterol ◽

Cell Plasma Membrane ◽

Cell Plasma ◽

Plasma Membrane Cholesterol

Download Full-text

Ultrastructure of Haustoria of Plant Pathogenic Fungi

Microscopy and Microanalysis ◽

10.1017/s1431927600025824 ◽

1998 ◽

Vol 4 (S2) ◽

pp. 1140-1141

Author(s):

C. W. Mims ◽

E. A. Richardson

Keyword(s):

Plasma Membrane ◽

Host Cell ◽

Pathogenic Fungi ◽

Life Cycles ◽

Plant Pathogenic Fungi ◽

Obligate Parasites ◽

Cell Plasma ◽

Different Types ◽

Host Cell Wall ◽

Host Plasma Membrane

Most plant pathogenic fungi that are obligate parasites produce haustoria which are thought to be involved in nutrient absorption. A haustorium is a specialized hyphal branch that penetrates the host cell wall and invaginates the host cell plasma membrane. The host plasma membrane ensheathing the haustorium is termed the extrahaustorial membrane. This presentation provides examples of different types of haustoria produced by plant pathogenic fungi. Species considered here are 1) Cronartium quercuum f. sp.fusiforme, the cause of fusiform gall rust of pine, 2) Puccinia arachidis, the cause of peanut rust1, 3) Uncinuliella australiana, the cause of powdery mildew of crape myrtle, 4) Exobasidium camelliae, a pathogen of Camellia sasanqua2, and 5) Cercosporidium personatum, the cause of late leaf spot of peanut.Rust fungi typically require two different host species to complete their life cycles. The dikaryotic phase of the rust life cycle consists of intercellular hyphae that give rise to specialized haustoria known as D-haustoria which are remarkably similar from one species to the next.

Download Full-text