title: Sulfolipid-1 biosynthesis restricts Mycobacterium tuberculosis growth in human macrophages.
abstract: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a highly evolved human pathogen characterized by its formidable cell wall. Many unique lipids and glycolipids from the Mtb cell wall are thought to be virulence factors that mediate host-pathogen interactions. An intriguing example is Sulfolipid-1 (SL-1), a sulfated glycolipid that has been implicated in Mtb pathogenesis, although no direct role for SL-1 in virulence has been established. Previously, we described the biochemical activity of the sulfotransferase Stf0 that initiates SL-1 biosynthesis. Here we show that a stf0-deletion mutant exhibits augmented survival in human but not murine macrophages, suggesting that SL-1 negatively regulates the intracellular growth of Mtb in a species-specific manner. Furthermore, we demonstrate that SL-1 plays a role in mediating the susceptibility of Mtb to a human cationic antimicrobial peptide in vitro, despite being dispensable for maintaining overall cell envelope integrity. Thus, we hypothesize that the species-specific phenotype of the stf0 mutant is reflective of differences in antimycobacterial effector mechanisms of macrophages.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Gilmore
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schelle
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Holsclaw
authors.forename: Clifton D
authors.initials: CD
authors.lastname: Leigh
authors.forename: Madhulika
authors.initials: M
authors.lastname: Jain
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Cox
authors.forename: Julie A
authors.initials: JA
authors.lastname: Leary
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000494:pharmacology; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D008055:Lipids / Q000096:biosynthesis* / Q000737:chemistry; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008055:Lipids; C015518:sulfolipids