Activation of Dendritic Cells by Liposomes Prepared from Phosphatidylinositol Mannosides from<i>Mycobacterium bovis</i>Bacillus Calmette-Guérin and Adjuvant Activity In Vivo

Sprott, G. Dennis; Dicaire, Chantal J.; Gurnani, Komal; Sad, Subash; Krishnan, Lakshmi

doi:10.1128/iai.72.9.5235-5246.2004

Cited by 62 publications

(47 citation statements)

References 31 publications

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“…At least one membrane lipid containing three fatty acyl chains, Gal-Glc-(N-acyl)GlcNGlc-diglyceride, from an extreme thermophile Thermus (30), is known to raise the thermal transition temperature of the membrane to close to 80°C, although the FAs are not of exceptional lengths (31). The physical behavior of acyl PIMs does not seem to have been investigated, but most intriguingly polar lipids from Mycobacterium bovis bacillus Calmette-Guérin, containing roughly 34% (by weight) Ac 1 /Ac 2 PIM 2 , were found to form liposomes only at temperatures above 55°C (32). The authors ascribe this high thermal transition point to the presence of C19:0 TS acid, but this may not be the whole explanation.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides

Bansal‐Mutalik

Nikaido

2014

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

211

232

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Mycobacterium species, including the human pathogen Mycobacterium tuberculosis, are unique among Gram-positive bacteria in producing a complex cell wall that contains unusual lipids and functions as a permeability barrier. Lipids in the cell wall were hypothesized to form a bilayer or outer membrane that would prevent the entry of chemotherapeutic agents, but this could not be tested because of the difficulty in extracting only the cell-wall lipids. We used reverse micellar extraction to achieve this goal and carried out a quantitative analysis of both the cell wall and the inner membrane lipids of Mycobacterium smegmatis. We found that the outer leaflet of the outer membrane contains a similar number of hydrocarbon chains as the inner leaflet composed of mycolic acids covalently linked to cell-wall arabinogalactan, thus validating the outer membrane model. Furthermore, we found that preliminary extraction with reverse micelles permitted the subsequent complete extraction of inner membrane lipids with chloroform-methanol-water, revealing that one-half of hydrocarbon chains in this membrane are contributed by an unusual lipid, diacyl phosphatidylinositol dimannoside. The inner leaflet of this membrane likely is composed nearly entirely of this lipid. Because it contains four fatty acyl chains within a single molecule, it may produce a bilayer environment of unusually low fluidity and may slow the influx of drugs, contributing to the general drug resistance phenotype of mycobacteria.Mycobacterium smegmatis | mycolic acid | phosphoinositides I t is now generally accepted that the organisms belonging to the Corynebacteria-Mycobacteria-Nocardia group are covered by a complex cell envelope containing the inner plasma membrane (IM), the peptidoglycan-arabinogalactan complex, and the outer membrane (OM) that is covalently linked to the arabinogalactan (1, 2). However, it has been nearly impossible to isolate the OM without contamination from IM components, and this makes the previous published studies on OM composition (3) and the models of OM (4, 5) less than convincing.The major limitation here has been the lack of a reliable technique capable of separating the IM and OM of mycobacteria. Although methods such as shaking with glass beads have been used in the past (3), these are random mechanical methods and an absolute selectivity cannot be achieved. Recently we used the technique of reverse micellar solution (RMS) extraction for Corynebacterium glutamicum cells and found that complete and selective removal of lipids from the OM was possible (6). Through the quantification of lipids we proved that a member of the Corynebacterineae had enough fatty acid chains beyond the peptidoglycan to form a complete OM bilayer barrier around the cell. In the process, we could assign the location of different lipid species to the OM and IM of the corynebacterial envelope. We now extend this approach to Mycobacterium smegmatis, which is commonly used as a model species of mycobacteria, a group including Mycobacterium tuberculosis tha...

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Section: Discussionmentioning

confidence: 99%

Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides

Bansal‐Mutalik

Nikaido

2014

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

211

232

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“…Nevertheless, they may be modified by specific molecules (e.g. mannosylated lipids) that recognize and bind to receptors expressed on APCs (17). Another important feature facilitating broad applications and up-scaling of the preparations is that antigen and DNA containing liposomes can be formulated as stable lyophilized products by addition of appropriate cryoprotectants (25).…”

Section: The Immunostimulatory Oligonucleotide Odn1668mentioning

confidence: 99%

“…Small unilamellar liposomes have a significant potential as delivery systems for the co-administration of antigens (peptides, lipopeptides) and of immunostimulatory adjuvants, including CpG oligonucleotides or DNA encoding antigens and/or immunostimulatory sequences (15). Additionally, the efficacy of liposome-based vaccines can be improved by targeting them more effectively and specifically to the APCs by exploiting various scavenger and other receptors as their targets (16)(17)(18) or by enhancing their cell uptake properties by modification with cell penetrating peptides (19).…”

Section: Introductionmentioning

confidence: 99%

Liposome Formulations of Hydrophobic Drugs

Schwendener

Schott

2009

Methods in Molecular Biology

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Here, we report methods of preparation of liposome vaccine formulations for the entrapment of antigenic peptides and antigen encoding plasmid DNAs. Two examples of liposomal vaccine formulations producing highly effective immune responses are given. Firstly, a formulation with encapsulated antigenic peptides derived from the hepatitis C virus NS4 and the core proteins, and secondly, the encapsulation of a plasmid DNA encoding the gp33 glycoprotein of the lymphocytic choriomeningitis virus (LCMV). Vaccination with liposomal HCV peptides in HLA-A2 transgenic mice by subcutaneous injections induced strong cytotoxic T cell responses as shown by lysis of human target cells expressing HCV proteins. The immunogenicity of the liposomal peptide vaccines was further enhanced by incorporation of immunostimulatory CpG oligonucleotide sequences, shown by a strong increase of the frequency of IFN-gamma secreting cells that persisted at high levels for long periods of time. With the LCMV model, we could show that upon intradermal injection, plasmid-DNA liposomes formed LCMV gp33 antigen depots facilitating long-lasting in vivo antigen loading of dendritic cells (DC), followed by a strong immune response. Our data show that liposomal formulations of peptide or plasmid-DNA vaccines are highly effective at direct in vivo antigen loading and activation of DC leading to protective antiviral and anti-tumor immune responses. 163Chapter 11

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“…Indeed, it has been suggested that this inner membrane may be "a bilayer environment of unusually low fluidity" [31] contributing to drug resistance. It was also noted [31] that the behaviour of PIM 2 liposomes had been found [66] to have behaviour suggestive of exceptional stability. It is now apparent that the inner mycobacterial plasma membrane is a highly specialised organelle, worthy of being distinguished with special nomenclature.…”

Section: Cell Envelope Organisationmentioning

confidence: 99%

Pathophysiological Implications of Cell Envelope Structure in Mycobacterium tuberculosis and Related Taxa

Minnikin¹,

Lee²,

Wu³

et al. 2015

Tuberculosis - Expanding Knowledge

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Activation of Dendritic Cells by Liposomes Prepared from Phosphatidylinositol Mannosides fromMycobacterium bovisBacillus Calmette-Guérin and Adjuvant Activity In Vivo

Cited by 62 publications

References 31 publications

Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides

Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides

Liposome Formulations of Hydrophobic Drugs

Pathophysiological Implications of Cell Envelope Structure in Mycobacterium tuberculosis and Related Taxa

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