Abstract
Lipids that are found only in the cell envelope of pathogenic mycobacteria, such as those containing multiple methyl-branched fatty acids, have long been thought to play a role in pathogenesis. Among these complex lipids, sulfolipids have been the most extensively studied over the last 50 years. The numerous biological effects exhibited by purified sulfolipids on phagocytic cells led to the idea that these molecules are probably important virulence factors facilitating the intracellular survival of Mycobacterium tuberculosis. However, definitive evidence to support this concept has been lacking. The recent construction of an isogenic sulfolipid-deficient mutant of M. tuberculosis H37Rv (Sirakova et al., J. Biol. Chem. 276:16833-16839, 2001) has for the first time provided the opportunity to directly assess the contribution of these complex lipids to pathogenesis. In the present study, we show that against all expectations, sulfolipid deficiency does not significantly affect the replication, persistence, and pathogenicity of M. tuberculosis H37Rv in mice and guinea pigs or in cultured macrophages.
MeSH Terms
Animals
Cell Line
Female
Guinea Pigs
Humans
Hypersensitivity, Delayed
Immunity, Cellular
In Vitro Techniques
Lipid Metabolism
Lipids/genetics
Lung/microbiology,pathology
Macrophages/microbiology
Mice
Mice, Inbred BALB C
Mutation
Mycobacterium tuberculosis/genetics,isolation & purification,pathogenicity,physiology
Tuberculosis, Pulmonary/etiology,immunology,microbiology,pathology
Virulence/genetics,physiology
Chemicals
Lipids
sulfolipids
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Rousseau Cécile
Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
Turner Oliver C
Rush Erik
Bordat Yann
Sirakova Tatiana D
Kolattukudy Pappachan E
Ritter Shannon
Orme Ian M
Gicquel Brigitte
Jackson Mary
References (25)
25 references, click to expand
-
Monocyte responses to sulfatide from Mycobacterium tuberculosis: inhibition of priming for enhanced release of superoxide, associated with increased secretion of interleukin-1 and tumor necrosis factor alpha, and altered protein phosphorylation.
Infect Immun. 1991 Aug;59(8):2542-8
PMID: 1649796
-
Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS).
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11554-9
PMID: 10500215
-
Mycobacterium tuberculosis phagosome.
Mol Microbiol. 1999 Mar;31(6):1603-9
PMID: 10209735
-
Cytochemical reaction of virulent tubercle bacilli.
Am Rev Tuberc. 1948 Dec;58(6):698
PMID: 18099848
-
Synergistic action of cord factor and mycobacterial sulfatides on mitochondria.
Infect Immun. 1974 Oct;10(4):733-41
PMID: 4214779
-
Lipids of putative relevance to virulence in Mycobacterium tuberculosis: phthiocerol dimycocerosate and the attenuation indicator lipid.
Infect Immun. 1974 Jan;9(1):150-8
PMID: 4271720
-
VIRULENCE AND MORPHOLOGICAL CHARACTERISTICS OF MAMMALIAN TUBERCLE BACILLI.
J Exp Med. 1947 Jul 31;86(2):175-84
PMID: 19871665
-
Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis.
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10955-60
PMID: 9380741
-
Inhibition of macrophage priming by sulfatide from Mycobacterium tuberculosis.
J Immunol. 1988 Jan 15;140(2):634-40
PMID: 2826597
-
SULFOLIPID FROM VIRULENT TUBERCLE BACILLI.
Proc Natl Acad Sci U S A. 1959 Dec;45(12):1801-4
PMID: 16590578
-
Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis.
Mol Microbiol. 1999 Oct;34(2):257-67
PMID: 10564470
-
Prevention of phagosome-lysosome fusion in cultured macrophages by sulfatides of Mycobacterium tuberculosis.
Proc Natl Acad Sci U S A. 1976 Jul;73(7):2510-4
PMID: 821057
-
Role of lipid content and hydrogen peroxide susceptibility in determining the guinea-pig virulence of Mycobacterium tuberculosis.
Br J Exp Pathol. 1982 Dec;63(6):693-700
PMID: 6817780
-
Polyanionic agents inhibit phagosome-lysosome fusion in cultured macrophages: a reply to the suggestion of Goren, Vatter, and Fiscus to the contrary.
J Leukoc Biol. 1988 Feb;43(2):179-82
PMID: 3422088
-
INFECTIVITY, PATHOGENICITY AND SULPHOLIPID FRACTION OF SOME INDIAN AND BRITISH STRAINS OF TUBERCLE BACILLI.
Tubercle. 1963 Dec;44:452-5
PMID: 14101326
-
Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv. I. Purification and properties.
Biochim Biophys Acta. 1970 Jun 9;210(1):116-26
PMID: 4989541
-
Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis.
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10961-6
PMID: 9380742
-
Effect of Mycobacterium tuberculosis-derived sulfolipid I on human phagocytic cells.
Infect Immun. 1988 Nov;56(11):2876-83
PMID: 2844675
-
Polyanionic agents do not inhibit phagosome-lysosome fusion in cultured macrophages.
J Leukoc Biol. 1987 Feb;41(2):122-9
PMID: 3468192
-
Immunopathogenesis of pulmonary granulomas in the guinea pig after infection with Mycobacterium tuberculosis.
Infect Immun. 2003 Feb;71(2):864-71
PMID: 12540568
-
The correlation of bacteriophage types of Mycobacterium tuberculosis with guinea-pig virulence and in vitro-indicators of virulence.
J Gen Microbiol. 1978 Sep;108(1):1-7
PMID: 80440
-
Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice.
Nature. 1999 Nov 4;402(6757):79-83
PMID: 10573420
-
Activation of human neutrophils by Mycobacterium tuberculosis-derived sulfolipid-1.
J Immunol. 1991 Apr 15;146(8):2730-6
PMID: 1849937
-
The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis.
J Biol Chem. 2001 May 18;276(20):16833-9
PMID: 11278910
-
Lipids of putative relevance to virulence in Mycobacterium tuberculosis: correlation of virulence with elaboration of sulfatides and strongly acidic lipids.
Infect Immun. 1974 Jan;9(1):142-9
PMID: 4202886