A sulfated metabolite produced by stf3 negatively regulates the virulence of Mycobacterium tuberculosis.
Sulfated molecules have been shown to modulate isotypic interactions between cells of metazoans and heterotypic interactions between bacterial pathogens or symbionts and their eukaryotic host cells. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces sulfated molecules that have eluded functional characterization for decades. We demonstrate here that a previously uncharacterized sulfated molecule, termed S881, is localized to the outer envelope of M. tuberculosis and negatively regulates the virulence of the organism in two mouse infection models. Furthermore, we show that the biosynthesis of S881 relies on the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate and a previously uncharacterized sulfotransferase, stf3. These findings extend the known functions of sulfated molecules as general modulators of cell-cell interactions to include those between a bacterium and a human host.
Molecular and Cell Biology, School of Public Health, and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Joseph D
JD
Mougous
Ryan H
RH
Senaratne
Christopher J
CJ
Petzold
Madhulika
M
Jain
Dong H
DH
Lee
Michael W
MW
Schelle
Michael D
MD
Leavell
Jeffery S
JS
Cox
Julie A
JA
Leary
Lee W
LW
Riley
Carolyn R
CR
Bertozzi
D000818:Animals; D005260:Female; D017353:Gene Deletion; D005798:Genes, Bacterial; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology; D014774:Virulence / Q000235:genetics / Q000502:physiology
D013431:Sulfates; D015238:Sulfotransferases