Membrane Cholesterol: a Crucial Molecule Affecting Interactions of Microbial Pathogens with Mammalian Cells

Goluszko, Pawel; Nowicki, B.

doi:10.1128/iai.73.12.7791-7796.2005

Cited by 129 publications

(96 citation statements)

References 64 publications

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“…Although no other pathogens are known to catabolize cholesterol, intracellular parasites interact with this compound for a variety of different purposes (38). Similarly, the degradation of cholesterol by M. tuberculosis might play important roles other than providing carbon and energy.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial persistence requires the utilization of host cholesterol

Pandey

Sassetti²

2008

Proc. Natl. Acad. Sci. U.S.A.

939

1,039

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A hallmark of tuberculosis is the ability of the causative agent, Mycobacterium tuberculosis , to persist for decades despite a vigorous host immune response. Previously, we identified a mycobacterial gene cluster, mce4 , that was specifically required for bacterial survival during this prolonged infection. We now show that mce4 encodes a cholesterol import system that enables M. tuberculosis to derive both carbon and energy from this ubiquitous component of host membranes. Cholesterol import is not required for establishing infection in mice or for growth in resting macrophages. However, this function is essential for persistence in the lungs of chronically infected animals and for growth within the IFN-γ-activated macrophages that predominate at this stage of infection. This finding indicates that a major effect of IFN-γ stimulation may be to sequester potential pathogens in a compartment devoid of more commonly used nutrients. The unusual capacity to catabolize sterols allows M. tuberculosis to circumvent this defense and thereby sustain a persistent infection.

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Section: Discussionmentioning

confidence: 99%

Mycobacterial persistence requires the utilization of host cholesterol

Pandey

Sassetti²

2008

Proc. Natl. Acad. Sci. U.S.A.

939

1,039

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“…Cholesterol maintains the membrane integrity and is preferentially confined to lipid rafts (Goluszko & Nowicki, 2005). The lipid-raft domains allow receptor clustering and are rich in signalling molecules, and thus are involved in receptor signalling.…”

Section: T Forsythia Invasion Requires Cholesterol-rich Lipid-raft Dmentioning

confidence: 99%

“…The entry of many pathogens into host cells involves cholesterol-and sphingolipid-rich membrane microdomains or lipid rafts (Goluszko & Nowicki, 2005;van der Goot & Harder, 2001;Zaas et al, 2005). Cholesterol maintains the membrane integrity and is preferentially confined to lipid rafts (Goluszko & Nowicki, 2005).…”

Section: T Forsythia Invasion Requires Cholesterol-rich Lipid-raft Dmentioning

confidence: 99%

Tannerella forsythia invasion in oral epithelial cells requires phosphoinositide 3-kinase activation and clathrin-mediated endocytosis

Mishima

Sharma

2011

Microbiology

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Tannerella forsythia, a Gram-negative anaerobe implicated in periodontitis, has been detected within human buccal epithelial cells and shown to invade oral epithelial cells in vitro. We have previously shown that this bacterium triggers host tyrosine kinase-dependent phosphorylation and actin-dependent cytoskeleton reorganization for invasion. On the bacterial side, the leucine-rich repeat cell-surface BspA protein is important for entry. The present study was undertaken to identify host signalling molecules during T. forsythia entry into human oral and cervical epithelial cells. Specifically, the roles of phosphatidylinositol 3-kinase (PI3K), Rho-family GTPases, cholesterol-rich membrane microdomains and the endocytic protein clathrin were investigated. For this purpose, cell lines were pretreated with chemical inhibitors or small interfering RNAs (siRNAs) that target PI3Ks, Rho GTPases, clathrin and cholesterol (a critical component of ‘lipid rafts’), and the resulting effects on T. forsythia uptake were determined. Our studies revealed that T. forsythia entry is dependent on host PI3K signalling, and that purified BspA protein causes activation of this lipid kinase. Bacterial entry also requires the cooperation of host Rac1 GTPase. Finally, our findings indicate an important role for clathrin and cholesterol-rich lipid microdomains in the internalization process

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“…A number of bacteria similarly exhibit cholesterol dependence, including Anaplasma phagocytophilum (Xiong et al 2009), Escherichia coli (Goluszko and Nowicki 2005), Mycobacterium (Gatfield and Pieters 2000), Staphylococcus aureus (Liu et al 2008), Salmonella (Hayward et al 2005), and Shigella (Hayward et al 2005), among others. Some, such as Mycobacterium tuberculosis, utilize cholesterol as a primary carbon source throughout the course of infection, such that degradation of this sterol is crucial for bacterial persistence (Miner et al 2009).…”

Section: Cholesterol and Infectionmentioning

confidence: 99%