Phthiocerols

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Typical phthiocerol lipid (PDIM) of the mycobacterial cell wall as a VDW model

Phthiocerols and phthiocerol lipids are a group of waxes that are produced exclusively by pathogenic mycobacteria and are part of their outermost cell wall . All in all, they are long-chain diols , their diesters with special long-chain fatty acids , and other derivatives such as ketones and glycosides . They are partly responsible for the fact that these germs are able to stop the innate immune response of the infected organism and to survive for a long time in macrophages ("latent infection"). A third of the world population is latently infected with mycobacteria.

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The main body of the phthiocerol lipids is phthiocerol with 33 to 41 carbon atoms, which has two adjacent hydroxyl groups and one methyl and one methoxy group. Esterified with it are two identical fatty acid residues, which can be 27 to 31 carbon atoms long and have two or three methyl residues in the 2,3,4-position. Since these fatty acids are called mycocerosinic acid and phthioceranic acid , diesters are called phthiocerol dimycocerosate ( DIM ) and phthiocerol diphthioceranate ( DIP ), respectively . Another phenyl derivative is abbreviated to PDIM and glycosides to PGL (phenolic glycolipid). The length of the chains and the composition of the glycosides is different in each bacterial species.

After the uptake ( phagocytosis ) of mycobacteria by the phagocytes of the infected organism, these are initially located in an endosome called a phagosome . The normal process would be gradual maturation of the endosome, followed by fusion with a lysosome . It has been shown that PDIM is a factor in Mycobacterium marinum that prevents this.

Use as a biomarker

Phthiocerols are on the one hand stable waxes, on the other hand specific for mycobacteria. They are therefore ideally suited to serve as an indicator of mycobacterial infection in mammalian skeletons. These properties could be confirmed in a study on almost 200-year-old corpses that were known to have died of tuberculosis.

Individual evidence

  1. Guenin-Macé L, Siméone R, Demangel C: Lipids of pathogenic Mycobacteria: contributions to virulence and host immune suppression . In: Transboundary and Emerging Diseases . 56, No. 6-7, August 2009, pp. 255-268. doi : 10.1111 / j.1865-1682.2009.01072.x . PMID 19486312 .
  2. Daffé M, Lane Elle MA: Distribution of phthiocerol diesters, phenolic mycosides and related compounds in mycobacteria . In: J. Gen. Microbiol. . 134, No. 7, July 1988, pp. 2049-2055. PMID 3149973 .
  3. Robinson N, Kolter T, Wolke M, Rybniker J, Hartmann P, Plum G: Mycobacterial phenolic glycolipid inhibits phagosome maturation and subverts the pro-inflammatory cytokine response . In: Traffic . 9, No. 11, November 2008, pp. 1936-1947. doi : 10.1111 / j.1600-0854.2008.00804.x . PMID 18764820 .
  4. Redman JE, Shaw MJ, Mallet AI, et al. : Mycocerosic acid biomarkers for the diagnosis of tuberculosis in the Coimbra Skeletal Collection . In: Tuberculosis (Edinb) . 89, No. 4, July 2009, pp. 267-277. doi : 10.1016 / j.tube.2009.04.001 . PMID 19493698 .