ArticleScientific reports2018
HadD, a novel fatty acid synthase type II protein, is essential for alpha- and epoxy-mycolic acid biosynthesis and mycobacterial fitness.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Mycobacterium tuberculosis lacking CtpF and MmpL7 transporters exhibits altered microbiological traits associated with virulence determinants.Archives of microbiology · 2026Article
- Exquisite specificity of Pks13 defines the essentiality of trehalose in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Protein-Mediated Virulence in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Functional characterization of GplA (MSMEG-0394) reveals a novel determinant of glycopeptidolipids homeostasis inFrontiers in microbiology · 2026Article
- Cell walls: a comparative view of the composition of cell surfaces of plants, algae, and microorganisms.Journal of experimental botany · 2025Review
- HadBD dehydratase from Mycobacterium tuberculosis fatty acid synthase type II: A singular structure for a unique function.Protein science : a publication of the Protein Society · 2024Article
- Lsr2 acts as a cyclic di-GMP receptor that promotes keto-mycolic acid synthesis and biofilm formation in mycobacteria.Nature communications · 2024Article
- TargetingRSC medicinal chemistry · 2023Review
- 1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex inACS infectious diseases · 2022Article
- Unveiling the Biosynthetic Pathway for Short Mycolic Acids in Nontuberculous Mycobacteria: Mycobacterium smegmatis MSMEG_4301 and Its Ortholog Mycobacterium abscessus MAB_1915 Are Essential for the Synthesis of α'-Mycolic Acids.Microbiology spectrum · 2022Article
- The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis.Scientific reports · 2022Article
- Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The aceE involves in mycolic acid synthesis and biofilm formation in Mycobacterium smegmatis.BMC microbiology · 2020Article
- Mechanisms of Resistance Associated with the Inhibition of the Dehydration Step of Type II Fatty Acid Synthase inACS infectious diseases · 2020Article
- Discovery of a novel dehydratase of the fatty acid synthase type II critical for ketomycolic acid biosynthesis and virulence of Mycobacterium tuberculosis.Scientific reports · 2020Article
- The MmpL3 interactome reveals a complex crosstalk between cell envelope biosynthesis and cell elongation and division in mycobacteria.Scientific reports · 2019Article
- Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages.Microorganisms · 2019Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycolic acids (MAs) have a strategic location within the mycobacterial envelope, deeply influencing its architecture and permeability, and play a determinant role in the pathogenicity of mycobacteria. The fatty acid synthase type II (FAS-II) multienzyme system is involved in their biosynthesis. A combination of pull-downs and proteomics analyses led to the discovery of a mycobacterial protein, HadD, displaying highly specific interactions with the dehydratase HadAB of FAS-II. In vitro activity assays and homology modeling showed that HadD is, like HadAB, a hot dog folded (R)-specific hydratase/dehydratase. A hadD knockout mutant of Mycobacterium smegmatis produced only the medium-size alpha'-MAs. Data strongly suggest that HadD is involved in building the third meromycolic segment during the late FAS-II elongation cycles, leading to the synthesis of the full-size alpha- and epoxy-MAs. The change in the envelope composition induced by hadD inactivation strongly altered the bacterial fitness and capacities to aggregate, assemble into colonies or biofilms and spread by sliding motility, and conferred a hypersensitivity to the firstline antimycobacterial drug rifampicin. This showed that the cell surface properties and the envelope integrity were greatly affected. With the alarmingly increasing case number of nontuberculous mycobacterial diseases, HadD appears as an attractive target for drug development.
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