ArticleMolecular microbiology2015
GacA is essential for Group A Streptococcus and defines a new class of monomeric dTDP-4-dehydrorhamnose reductases (RmlD).
Article in Molecular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- The "Cairo Accord"- towards the eradication of RHD: revisited (2026).Frontiers in cardiovascular medicine · 2026Review
- Natural variation of the streptococcal group A carbohydrate biosynthesis genes impacts host-pathogen interaction.Microbial genomics · 2025Article
- Review
- Harzianic acid exerts antimicrobial activity against Gram-positive bacteria and targets the cell membrane.Frontiers in microbiology · 2024Article
- Progress towards a glycoconjugate vaccine against Group A Streptococcus.NPJ vaccines · 2023Review
- Antibiotics and Carbohydrate-Containing Drugs Targeting Bacterial Cell Envelopes: An Overview.Pharmaceuticals (Basel, Switzerland) · 2022Review
- PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides.Nature communications · 2022Article
- Disruption of protein rhamnosylation affects theCell surface (Amsterdam, Netherlands) · 2021Article
- Immunobiology of the Classical Lancefield Group A Streptococcal Carbohydrate Antigen.Infection and immunity · 2021Article
- Examining the Distribution and Impact of Single-Nucleotide Polymorphisms in the Capsular Locus of Streptococcus pneumoniae Serotype 19A.Infection and immunity · 2021Article
- Molecular basis for recognition of the Group A Carbohydrate backbone by the PlyC streptococcal bacteriophage endolysin.The Biochemical journal · 2021Article
- Racemases and epimerases operating through a 1,1-proton transfer mechanism: reactivity, mechanism and inhibition.Chemical Society reviews · 2021Review
- Cell wall polysaccharides of Gram positive ovococcoid bacteria and their role as bacteriophage receptors.Computational and structural biotechnology journal · 2021Review
- iTRAQ-based quantitative analysis reveals the mechanism underlying the changes in physiological activity in a glutamate racemase mutant strain of Streptococcus mutans UA159.Molecular biology reports · 2020Article
- Biosynthetic access to the rare antiarose sugarChemical science · 2020Article
- Repurposing the Streptococcus mutans CRISPR-Cas9 System to Understand Essential Gene Function.PLoS pathogens · 2020Article
- Disruption of l-Rhamnose Biosynthesis Results in Severe Growth Defects in Streptococcus mutans.Journal of bacteriology · 2020Article
- Group A, B, C, and GThe Journal of biological chemistry · 2019Article
- Discovery of an RmlC/D fusion protein in the microalgaThe Journal of biological chemistry · 2019Article
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
The sugar nucleotide dTDP-L-rhamnose is critical for the biosynthesis of the Group A Carbohydrate, the molecular signature and virulence determinant of the human pathogen Group A Streptococcus (GAS). The final step of the four-step dTDP-L-rhamnose biosynthesis pathway is catalyzed by dTDP-4-dehydrorhamnose reductases (RmlD). RmlD from the Gram-negative bacterium Salmonella is the only structurally characterized family member and requires metal-dependent homo-dimerization for enzymatic activity. Using a biochemical and structural biology approach, we demonstrate that the only RmlD homologue from GAS, previously renamed GacA, functions in a novel monomeric manner. Sequence analysis of 213 Gram-negative and Gram-positive RmlD homologues predicts that enzymes from all Gram-positive species lack a dimerization motif and function as monomers. The enzymatic function of GacA was confirmed through heterologous expression of gacA in a S. mutans rmlD knockout, which restored attenuated growth and aberrant cell division. Finally, analysis of a saturated mutant GAS library using Tn-sequencing and generation of a conditional-expression mutant identified gacA as an essential gene for GAS. In conclusion, GacA is an essential monomeric enzyme in GAS and representative of monomeric RmlD enzymes in Gram-positive bacteria and a subset of Gram-negative bacteria. These results will help future screens for novel inhibitors of dTDP-L-rhamnose biosynthesis.
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