Detection of Antimycolic Acid Antibodies by Liposomal Biosensors

Lemmer, Yolandy; Thanyani, Simon T.; Vrey, Pieter Jakobus; Driver, Cathryn H S; Venter, L.; Wyngaardt, Sandra Van; Bokum, Annemieke Ten; Ozoemena, Kenneth I.; Pilcher, Lynne A.; Fernig, David G.; Stoltz, Anton; Swai, Hulda; Verschoor, J.A.

doi:10.1016/s0076-6879(09)64005-2

Cited by 20 publications

(12 citation statements)

References 27 publications

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“…Preparation of the ELISA plates was done as previously described with modifications [28,52,53]. Where liposomes were used in the inhibition of serum anti-MA antibodies in literature (75 μg MA/1 μl of serum), we used MA-NPs (2 μg MA/1 μl of serum).…”

Section: Immuno Detection Of Ma On Particle Surfacesmentioning

confidence: 99%

“…An attractive hypothesis would be that the MA present on the external surface of the NPs may interact with anti-MA antibodies in the vicinity of the sites of infection to cause a localised immune complex that may enhance uptake of the NPs in the infected and surrounding uninfected macrophages. MA could also target cholesterol present in the plasma membrane of uninfected or infected macrophages [25,26] and, more interestingly, in the membrane of phagosomes in which pathogenic mycobacteria are harboured [27], by means of its attraction to cholesterol [20,21,28].…”

Section: Introductionmentioning

confidence: 99%

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Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Lemmer

Kalombo

Pietersen

et al. 2015

Journal of Controlled Release

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The appearance of drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologies might alleviate the limitations of current therapies, we have designed a new nanoformulation for use as an anti-TB drug delivery system. It consists of incorporating mycobacterial cell wall mycolic acids (MA) as targeting ligands into a drug-encapsulating Poly dl-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bone marrow-derived mouse macrophages, either uninfected or infected with different mycobacterial strains (Mycobacterium avium, Mycobacterium bovis BCG or Mtb), were exposed to encapsulated isoniazid-PLGA nanoparticles (NPs) using MA as a targeting ligand. The fate of the NPs was monitored by electron microscopy. Our study showed that i) the inclusion of MA in the nanoformulations resulted in their expression on the outer surface and a significant increase in phagocytic uptake of the NPs; ii) nanoparticle-containing phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; and iii) nanoparticle-containing phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.

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Section: Immuno Detection Of Ma On Particle Surfacesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Lemmer

Kalombo

Pietersen

et al. 2015

Journal of Controlled Release

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“…There remained, however, an overlap between the anti-MA antibody binding signals between TB patient and control sera that made the ELISA outcome not adequately accurate as a diagnostic indicator. One way to get around this problem was to employ modern antibody detection technology where antibody binding is detected in real time, thereby increasing the sensitivity of the reaction [92,130]. These authors also showed that human TB patient anti-MA antibodies included IgG, by demonstrating that a significant part of the anti-MA antibody activity could be purified with Protein A affinity chromatography, known to be insensitive for IgM.…”

Section: The Human Antibody Response To Mycolic Acidsmentioning

confidence: 99%

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

Verschoor

Baird

Grooten

2012

Progress in Lipid Research

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Mycolic acids constitute the waxy layer of the outer cell wall of Mycobacterium spp and a few other genera. They are diverse in structure, providing a unique chromatographic foot-print for almost each of the more than seventy Mycobacterium species. Although mainly esterified to cell wall arabinogalactan, trehalose or glucose, some free mycolic acid is secreted during in vitro growth of M. tuberculosis. In M. tuberculosis, alpha-, keto-and methoxy-mycolic acids are the main classes, each differing in their ability to attract neutrophils, induce foamy macrophages or adopt an antigenic structure for antibody recognition. Of interest is their particular relationship to cholesterol, discovered by their ability to attract cholesterol, to bind Amphotericin B or to be recognised by monoclonal antibodies that cross-react with cholesterol. The structural elements that determine this diverse functionality include the carboxylic acid in the mycolic motif, as well as the nature and stereochemistry of the two functional groups in the merochain. The functional diversity of mycolic acid classes implies that much information may be contained in the selective expression and secretion of mycolic acids to establish tuberculosis after infection of the host. Their cholesteroid nature may relate to how they utilize host cholesterol for their persistent survival.

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“…Part of the problem in this case may be that some of the antibodies present are cross-reactive to mycolic acids and cholesterol [Benadie, 2008]. In order to seek to improve sensitivity and specificity, Verschoor et al have developed a method based on the use of mycolic acid containing liposomes in an inhibition assay using surface Plasmon resonance [Verschoor, 2010;Thanyani et al, 2008;Lemmer et al, 2009]. One singular advantage of this method is that the signals are retained in HIV patients [Schleicher et al, 2002].…”

Section: Scheme 1: Common Classes Of Mycolic Acids In Mycobacteriamentioning

confidence: 99%

Thiol modified mycolic acids

Balogun

Huws

Sirhan

et al. 2013

Chemistry and Physics of Lipids

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Detection of Antimycolic Acid Antibodies by Liposomal Biosensors

Cited by 20 publications

References 27 publications

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

Thiol modified mycolic acids

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