ArticlePLoS pathogens2015
Lipidomic analysis links mycobactin synthase K to iron uptake and virulence in M. tuberculosis.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
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- Pheno- and genotypic iron acquisition of non-aureus staphylococci: a scoping review of literature with a focus on bovine mastitis.Veterinary research · 2025Article
- Redefining the role of the EryM acetyltransferase in natural product biosynthetic pathways.Structure (London, England : 1993) · 2025Article
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- Phenotypic and genotypic assessment of iron acquisition in diverse bovine-associated non-aureus staphylococcal strains.Veterinary research · 2024Article
- Iron Status and Supplementation during Tuberculosis.Microorganisms · 2023Review
- The role ofFrontiers in cellular and infection microbiology · 2023Review
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- A periplasmic cinched protein is required for siderophore secretion and virulence of Mycobacterium tuberculosis.Nature communications · 2022Article
- Iron deprivation enhances transcriptional responses toFrontiers in microbiology · 2022Article
- The Iron Response ofFrontiers in cellular and infection microbiology · 2022Review
- Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress.Molecular microbiology · 2021Article
- Siderophore-Mediated Iron Acquisition Plays a Critical Role in Biofilm Formation and Survival ofFrontiers in medicine · 2021Article
- A systematic evaluation of Mycobacterium tuberculosis Genome-Scale Metabolic Networks.PLoS computational biology · 2020Article
- Detection of Tuberculosis by The Analysis of Exhaled Breath Particles with High-resolution Mass Spectrometry.Scientific reports · 2020Article
- Heme and hemoglobin utilization by Mycobacterium tuberculosis.Nature communications · 2019Article
- Genome-wide Phenotypic Profiling Identifies and Categorizes Genes Required for Mycobacterial Low Iron Fitness.Scientific reports · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The prolonged survival of Mycobacterium tuberculosis (M. tb) in the host fundamentally depends on scavenging essential nutrients from host sources. M. tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores, synthesized by mycobactin synthases (Mbt). Although a general mechanism for mycobactin biosynthesis has been proposed, the biological functions of individual mbt genes remain largely untested. Through targeted gene deletion and global lipidomic profiling of intact bacteria, we identify the essential biochemical functions of two mycobactin synthases, MbtK and MbtN, in siderophore biosynthesis and their effects on bacterial growth in vitro and in vivo. The deletion mutant, ΔmbtN, produces only saturated mycobactin and carboxymycobactin, demonstrating an essential function of MbtN as the mycobactin dehydrogenase, which affects antigenicity but not iron uptake or M. tb growth. In contrast, deletion of mbtK ablated all known forms of mycobactin and its deoxy precursors, defining MbtK as the essential acyl transferase. The mbtK mutant showed markedly reduced iron scavenging and growth in vitro. Further, ΔmbtK was attenuated for growth in mice, demonstrating a non-redundant role of hydroxamate siderophores in virulence, even when other M. tb iron scavenging mechanisms are operative. The unbiased lipidomic approach also revealed unexpected consequences of perturbing mycobactin biosynthesis, including extreme depletion of mycobacterial phospholipids. Thus, lipidomic profiling highlights connections among iron acquisition, phospholipid homeostasis, and virulence, and identifies MbtK as a lynchpin at the crossroads of these phenotypes.
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