ArticlePLoS pathogens2013
Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
144 citing papers in PubMed, 253 citations in OpenAlex.
- Structure, assembly, and mechanism of the MmpL family of transporters.Microbiology and molecular biology reviews : MMBR · 2026Review
- Tobramycin enhancesProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Article
- Bacterial Siderophore Production in Metal-Rich Environments: Underexplored Sources of Siderophores and Insights into Bioremediation.Journal of natural products · 2026Review
- Article
- Structural elucidation of the hexameric MmpS4-MmpL4 complex frombioRxiv : the preprint server for biology · 2026Article
- Contribution of Proteins to Membrane and Cell Wall Structures in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Transmission of bedaquiline-resistant Mycobacterium tuberculosis in KwaZulu-Natal, South Africa.American journal of respiratory and critical care medicine · 2026Article
- Article
- Siderophores and secondary metabolites produced byMicrobiology (Reading, England) · 2025Article
- Genomic characterisation of recurrent Mycobacterium avium isolates from chronically infected patients reveals patterns of within-host evolution.Genome medicine · 2025Article
- Structural and functional analysis of theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.Science advances · 2025Article
- VLX600, an anticancer iron chelator, exerts antimicrobial effects onMicrobiology spectrum · 2025Article
- Structure and assembly of the MmpL5/MmpS5 efflux transporter from Mycobacterium tuberculosis.Nature communications · 2025Article
- Verapamil and its metabolite norverapamil inhibit theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance in Mycobacterium abscessus.PLoS pathogens · 2025Article
- Properties and antibacterial effectiveness of metal-ion doped borate-based bioactive glasses.Future microbiology · 2025Review
- High Prevalence of atpE Mutations in Bedaquiline-Resistant Mycobacterium tuberculosis Isolates, Russia.Emerging infectious diseases · 2025Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Iron is an essential nutrient for most bacterial pathogens, but is restricted by the host immune system. Mycobacterium tuberculosis (Mtb) utilizes two classes of small molecules, mycobactins and carboxymycobactins, to capture iron from the human host. Here, we show that an Mtb mutant lacking the mmpS4 and mmpS5 genes did not grow under low iron conditions. A cytoplasmic iron reporter indicated that the double mutant experienced iron starvation even under high-iron conditions. Loss of mmpS4 and mmpS5 did not change uptake of carboxymycobactin by Mtb. Thin layer chromatography showed that the ΔmmpS4/S5 mutant was strongly impaired in biosynthesis and secretion of siderophores. Pull-down experiments with purified proteins demonstrated that MmpS4 binds to a periplasmic loop of the associated transporter protein MmpL4. This interaction was corroborated by genetic experiments. While MmpS5 interacted only with MmpL5, MmpS4 interacted with both MmpL4 and MmpL5. These results identified MmpS4/MmpL4 and MmpS5/MmpL5 as siderophore export systems in Mtb and revealed that the MmpL proteins transport small molecules other than lipids. MmpS4 and MmpS5 resemble periplasmic adapter proteins of tripartite efflux pumps of Gram-negative bacteria, however, they are not only required for export but also for efficient siderophore synthesis. Membrane association of MbtG suggests a link between siderophore synthesis and transport. The structure of the soluble domain of MmpS4 (residues 52-140) was solved by NMR and indicates that mycobacterial MmpS proteins constitute a novel class of transport accessory proteins. The bacterial burden of the mmpS4/S5 deletion mutant in mouse lungs was lower by 10,000-fold and none of the infected mice died within 180 days compared to wild-type Mtb. This is the strongest attenuation observed so far for Mtb mutants lacking genes involved in iron utilization. In conclusion, this study identified the first components of novel siderophore export systems which are essential for virulence of Mtb.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.