Phthiocerol dimycocerosate transport is required for resisting interferon-gamma-independent immunity.
Nitric oxide (NO), which is an important component of immunity to Mycobacterium tuberculosis, has both cytotoxic and immune regulatory functions. We examined the way that this molecule interacts with M. tuberculosis in vivo by screening for bacterial mutations that alter growth in mice that are unable to produce inducible NO synthase (iNOS), the dominant source of NO during infection. We found that very few bacterial genes appeared to be specifically required for resistance to NO in vivo. Instead, mutations in several virulence factors caused greater attenuation in the absence of iNOS. Among these were mutants incapable of transporting the lipid phthiocerol dimycocerosate (PDIM). Although PDIM has been implicated in NO defense, this result indicates that PDIM has other roles during infection. We additionally found that PDIM transport is required for virulence in mice lacking interferon-gamma . Thus, PDIM is important for resisting an interferon-gamma-independent mechanism of immunity.
Murry
Jeffrey P
JP
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Pandey
Amit K
AK
Sassetti
Christopher M
CM
Rubin
Eric J
EJ
D000818:Animals; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008055:Lipids / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D014774:Virulence
D004269:DNA, Bacterial; D008055:Lipids; C008901:phthiocerol dimycocerosate; D007371:Interferon-gamma