ArticleProceedings of the National Academy of Sciences of the United States of America2003
MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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130 citing papers in PubMed, 244 citations in OpenAlex.
- Structure, assembly, and mechanism of the MmpL family of transporters.Microbiology and molecular biology reviews : MMBR · 2026Review
- Sulfolipid-1 fromJournal of neurophysiology · 2026Article
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- Genome and drug resistance analysis ofFrontiers in microbiology · 2026Article
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- MmpL12 transports lipooligosaccharides and impacts virulence inMicrobiology (Reading, England) · 2025Article
- Performance of direct detection ofMicrobiology spectrum · 2025Article
- Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.Science advances · 2025Article
- An unusual genetic switch controlsbioRxiv : the preprint server for biology · 2025Article
- Genotyping and drug susceptibility patterns of Mycobacterium avium subsp. hominissuis isolates from different hosts.Scientific reports · 2025Article
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- Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.PLoS biology · 2024Article
- A Loss of Function in LprG-Rv1410c Homologues Attenuates Growth during Biofilm Formation inPathogens (Basel, Switzerland) · 2023Article
- Intricate link between siderophore secretion and drug efflux inAntimicrobial agents and chemotherapy · 2023Article
- Clinical strains of Mycobacterium tuberculosis exhibit differential lipid metabolism-associated transcriptome changes in in vitro cholesterol and infection models.Pathogens and disease · 2023Article
- The Key Roles ofFrontiers in microbiology · 2023Article
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- Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains.Nature communications · 2022Article
- The Iron Response ofFrontiers in cellular and infection microbiology · 2022Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis, the causative agent of human tuberculosis, is unique among bacterial pathogens in that it displays a wide array of complex lipids and lipoglycans on its cell surface. One of the more remarkable lipids is a sulfated glycolipid, termed sulfolipid-1 (SL-1), which is thought to mediate specific host-pathogen interactions during infection. However, a direct role for SL-1 in M. tuberculosis virulence has not been established. Here we show that MmpL8, a member of a large family of predicted lipid transporters in M. tuberculosis, is required for SL-1 production. The accumulation of an SL-1 precursor, termed SL(1278), in mmpL8 mutant cells indicates that MmpL8 is necessary for an intermediate step in the SL-1 biosynthesis pathway. We use a novel fractionation procedure to demonstrate that SL-1 is present on the cell surface, whereas SL(1278) is found exclusively in more internal layers. Importantly, we show that mmpL8 mutants are attenuated for growth in a mouse model of tuberculosis. However, SL-1 per se is not required for establishing infection as pks2 mutants, which are defective in an earlier step in SL-1 biosynthesis, have no obvious growth defect. Thus, we hypothesize that either MmpL8 transports molecules in addition to SL-1 that mediate host-pathogen interactions or the accumulation of SL(1278) in mmpL8 mutant cells interferes with other pathways required for growth during the early stages of infection.
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