1 research outputs found
Sulfolipid-1 Biosynthesis Restricts <i>Mycobacterium tuberculosis</i> Growth in Human Macrophages
<i>Mycobacterium tuberculosis</i> (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 <i>stf0</i>-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 <i>in vitro</i>, despite being dispensable for maintaining overall cell envelope
integrity. Thus, we hypothesize that the species-specific phenotype
of the <i>stf0</i> mutant is reflective of differences in
antimycobacterial effector mechanisms of macrophages