Temperature dependence of the Langmuir monolayer packing of mycolic acids from Mycobacterium tuberculosis

Villeneuve, Masumi; Kawai, Mizuo; Kanashima, Hideki; Watanabe, Motoko; Minnikin, David E.; Nakahara, Hiroyuki

doi:10.1016/j.bbamem.2005.07.005

Cited by 68 publications

(81 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As reported previously, Monte Carlo calculations showed that most of the MAs from the slow-growing mycobacteria tend to form folded conformations, an energetically more stable form, in which the four methylene chain segments are packed together more or less in parallel, hereafter referred to as a 'W-form' conformation (Villeneuve et al, 2005(Villeneuve et al, , 2007(Villeneuve et al, , 2010. However, the thermodynamic studies of the Langmuir monolayers show that different MAs have different conformational behaviours (Villeneuve et al, 2005(Villeneuve et al, , 2007(Villeneuve et al, , 2010.…”

Section: Introductionmentioning

confidence: 74%

“…However, the thermodynamic studies of the Langmuir monolayers show that different MAs have different conformational behaviours (Villeneuve et al, 2005(Villeneuve et al, , 2007(Villeneuve et al, , 2010. Thus, non-oxygenated a-MAs take W-form conformations only in a limited area where both temperatures and surface pressures are very low (Villeneuve et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, non-oxygenated a-MAs take W-form conformations only in a limited area where both temperatures and surface pressures are very low (Villeneuve et al, 2010). Oxygenated MAs, especially keto-MAs, generally form more stable W-form conformations partly owing to the likely hydration of the keto group on the water surface (Villeneuve et al, 2005(Villeneuve et al, , 2007. Our previous monolayer studies showed that the MeO-MAs and keto-MAs from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and Mycobacterium tuberculosis (Mtb) Aoyama B had distinct conformational behaviours, including different features of the surface pressure (p) vs mean molecular area (A) isotherms (Villeneuve et al, 2005(Villeneuve et al, , 2007.…”

Section: Introductionmentioning

confidence: 99%

“…Oxygenated MAs, especially keto-MAs, generally form more stable W-form conformations partly owing to the likely hydration of the keto group on the water surface (Villeneuve et al, 2005(Villeneuve et al, , 2007. Our previous monolayer studies showed that the MeO-MAs and keto-MAs from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and Mycobacterium tuberculosis (Mtb) Aoyama B had distinct conformational behaviours, including different features of the surface pressure (p) vs mean molecular area (A) isotherms (Villeneuve et al, 2005(Villeneuve et al, , 2007. The constituent molecules of MeO-MAs and ketoMAs from BCG and those from Mtb are essentially the same, differing only in the ratios of the cis-and trans-cyclopropyl groups.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Conformational folding of mycobacterial methoxy- and ketomycolic acids facilitated by α-methyl trans-cyclopropane groups rather than cis-cyclopropane units

et al. 2013

Self Cite

View full text Add to dashboard Cite

Conformational folding of mycobacterial methoxyand ketomycolic acids facilitated by a-methyl trans-cyclopropane groups rather than cis-cyclopropane units The oxygenated long-chain mycolic acids from many mycobacteria are characterized by the presence of mid-chain cyclopropane groups, which can have either cis-configuration or transconfiguration with an adjacent methyl branch. To determine the effect of these functional groups on mycolic acid conformation, surface pressure (p) versus mean molecular area isotherms of methoxy-(MeO-) mycolic acids (MAs) from Mycobacterium kansasii, Mycobacterium tuberculosis (Mtb) Canetti and Mtb H37Ra, and of keto-MAs from Mycobacterium avium-intracellulare complex (MAC) and Mtb H37Ra were recorded and analysed. The MeO-and keto-MAs from Mtb H37Ra, containing scarcely any trans-cyclopropyl groups, apparently took no fully folded 'Wform' conformations. Keto-MA from MAC, whose trans-cyclopropyl group content is nearly 90 %, showed a very solid W-form conformation. MeO-MAs from M. kansasii and Mtb Canetti gave stable W-form conformations at lower temperatures and surface pressures and extended conformations at higher temperatures and surface pressures; their W-form conformation was not as stable as expected from their cis-cyclopropyl group content, probably because they had a wide range of constituent homologues. Energy level calculations of cis-or a-methyl transcyclopropane-containing model molecules and computer simulation studies confirmed the superior folding properties of the latter functional unit. The present results were compared with those of MeO-and keto-MAs from Mtb and from M. bovis Bacillus Calmette-Gué rin (BCG) reported previously. Among the oxygenated MAs, those having higher trans-cyclopropane content tended to take W-form conformations more firmly, implying that the meromycolate proximal intrachain a-methyl trans-cyclopropane groups facilitated MA folding more than cis-cyclopropane groups. INTRODUCTIONMycobacterial mycolic acids (MAs) are characteristic components of the mycobacterial cell envelope, where major proportions of the acids are covalently bonded to the cell wall penta-arabinosyl units (Minnikin, 1982;Draper, 1998;Dmitriev et al., 2000). As shown in the general structure below, MAs are long chain 2-alkyl branched, 3-hydroxy fatty acids, with two intra-chain groups X and Y in the major chain, termed the meromycolate chain:According to the distal intra-chain functional group X, the MAs in this study are classified into three major groups: a nonoxygenated a-, and two oxygenated groups, methoxy-(MeO-) and keto-MAs. According to the proximal intra-chain group Abbreviations: BCG, Mycobacterium bovis Bacillus Calmette-Gué rin; MAC, Mycobacterium avium-intracellulare complex; MA, mycolic acid; Mtb, Mycobacterium tuberculosis.

show abstract

Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Conformational folding of mycobacterial methoxy- and ketomycolic acids facilitated by α-methyl trans-cyclopropane groups rather than cis-cyclopropane units

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been previously demonstrated that the regular spacing of functional groups in mycobacterial mycolic acids facilitates folding and packing in monolayer studies (Villeneuve et al, 2005(Villeneuve et al, , 2007. This folding ability is important in allowing mycolic acids to be accommodated within the dimensions of the mycobacterial outer membrane, revealed for the first time by cryo-electron microscopy (Zuber et al, 2008).…”

Section: Discussionmentioning

confidence: 95%

Structural elucidation and genomic scrutiny of the C60–C100 mycolic acids of Segniliparus rotundus

et al. 2013

View full text Add to dashboard Cite

Mycolic acids, very long-chain a-alkyl, b-hydroxylated fatty acids, occur in the members of the order Corynebacteriales where their chain lengths (C 26 -C 88 ) and structural features (oxygen functions, cis or trans double bonds, cyclopropane rings and methyl branches) are genus-and species-specific. The molecular composition and structures of the mycolic acids of two species belonging to the genus Segniliparus were determined by a combination of modern analytical chemical techniques, which include MS and NMR. They consist of mono-ethylenic C 62-C 64 (a9), di-ethylenic C 77 -C 79 (a) and extremely long-chain mycolic acids (a + ) ranging from 92 to 98 carbon atoms and containing three unsaturations, cis and/or trans double bonds and/or cyclopropanes. The double bonds in each class of mycolic acids were positioned by oxidative cleavage and exhibit locations similar to those of a-and a9-mycolic acids of mycobacteria. For the ultralong chain a-mycolic acids, the three double bonds were located at equally spaced carbon intervals (C 13 -C 16 ), with the methyl branches adjacent to the proximal and distal trans double bonds. Examination of the Segniliparus rotundus genome compared with those of other members of the Corynebacteriales indicated two obvious differences in genes encoding the elongation fatty acid (FAS-II) enzymes involved in the biosynthesis of mycolic acids: the organization of 3-ketoacyl-ACP synthases (KasA and KasB) and (3R)-hydroxyacyl-ACP dehydratases (HadAB/ BC), on one hand, and the presence of two copies of the hadB gene encoding the catalytic domain of the latter enzyme type, on the other. This observation is discussed in light of the most recent data accumulated on the biosynthesis of this hallmark of Corynebacteriales.

show abstract

Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern

et al. 2010

View full text Add to dashboard Cite

Mycolic acids (MAs) occur in the cell wall of Mycobacterium tuberculosis as variable mixtures of different classes and chain lengths. Here, we address the relationship between the structure and its inflammatory function of this virulence factor using single synthetic MA isomers, differing in oxygenation class and cis- versus α-methyl-trans proximal cyclopropane orientation. Analysis of bronchoalveolar inflammation, lung histopathology and alveolar macrophage transcription revealed a strong dependence on these meromycolic chemistries of mouse pulmonary inflammation in response to intratracheal treatments with MAs. Whereas α-MA was inert, oxygenated methoxy- and keto-MA with cis-cyclopropane stereochemistry elicited solid to mild inflammatory responses respectively. In trans-cyclopropane orientation, methoxy-MA partially lost its inflammatory activity and keto-MA exerted anti-inflammatory alternative activation of alveolar macrophages and counteracted cis-methoxy-MA induced airway inflammation. The differential innate immune activities of MAs demonstrated here, dependent on oxygenation class and cis versus α-methyl-trans cyclopropane chemistry, identify a novel means for M. tuberculosis to steer host immune responses during infection.

show abstract

Temperature dependence of the Langmuir monolayer packing of mycolic acids from Mycobacterium tuberculosis

Cited by 68 publications

References 20 publications

Conformational folding of mycobacterial methoxy- and ketomycolic acids facilitated by α-methyl trans-cyclopropane groups rather than cis-cyclopropane units

Conformational folding of mycobacterial methoxy- and ketomycolic acids facilitated by α-methyl trans-cyclopropane groups rather than cis-cyclopropane units

Structural elucidation and genomic scrutiny of the C60–C100 mycolic acids of Segniliparus rotundus

Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern

Contact Info

Product

Resources

About