Deficiency in mycolipenate- and mycosanoate-derived acyltrehaloses enhances early interactions of Mycobacterium tuberculosis with host cells.
Lipids that are uniquely found in the cell envelope of pathogenic mycobacteria, such as those containing multiple methyl-branched long-chain fatty acids, have long been thought to play a role in host-pathogen interactions. The recent construction by Dubey et al. (2002) Mol Microbiol 45: 1451-1459, of a Mycobacterium tuberculosis mutant that is deficient in the synthesis of the di- and tri-methylbranched fatty acids, mycolipenates and mycosanoates, found in some forms of diacyltrehaloses (DAT) and polyacyltrehaloses (PAT) provided the opportunity to assess the contribution of these complex lipids to pathogenesis directly. We provide evidence that DAT/PAT deficiency affects the surface global composition of the mycobacterial cell envelope improving the efficiency with which M. tuberculosis binds to and enters phagocytic and non-phagocytic host cells. Interestingly, this property did not affect the overall replication and persistence of the tubercle bacillus in the lungs, spleen and liver of mice infected via the respiratory or intravenous route.
Rousseau
Cécile
C
Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
Neyrolles
Olivier
O
Bordat
Yann
Y
Giroux
Stéphanie
S
Sirakova
Tatiana D
TD
Prevost
Marie-Christine
MC
Kolattukudy
Pappachan E
PE
Gicquel
Brigitte
B
Jackson
Mary
M
D000818:Animals; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry; D005260:Female; D006017:Glycolipids / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D009171:Mycolic Acids / Q000737:chemistry*; D010587:Phagocytosis / Q000502:physiology; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000502:physiology*; D013154:Spleen / Q000382:microbiology; D014199:Trehalose / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D014376:Tuberculosis / Q000378:metabolism / Q000473:pathology
D005227:Fatty Acids; D006017:Glycolipids; D009171:Mycolic Acids; D011135:Polysaccharides, Bacterial; D014199:Trehalose