Related Experiment Video

Updated: May 22, 2026

Isolation of Lipoprotein Particles from Chicken Egg Yolk for the Study of Bacterial Pathogen Fatty Acid Incorporation into Membrane Phospholipids
11:59

Isolation of Lipoprotein Particles from Chicken Egg Yolk for the Study of Bacterial Pathogen Fatty Acid Incorporation into Membrane Phospholipids

Published on: May 15, 2019

Staphylococcus aureus FabI: inhibition, substrate recognition, and potential implications for in vivo essentiality

Johannes Schiebel1, Andrew Chang, Hao Lu

  • 1Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, D-97080 Würzburg, Germany.

Structure (London, England : 1993)
|May 15, 2012
PubMed

Insights

Novel antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) are crucial. Researchers revealed the enoyl-ACP reductase (saFabI) enzyme’s flexibility, explaining its role in fatty acid synthesis and identifying it as a promising drug target.

Area of Science:

  • Biochemistry
  • Microbiology
  • Drug Discovery

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a global health threat, necessitating new antibiotic strategies.
  • The enoyl-ACP reductase (saFabI) enzyme is vital for Staphylococcus aureus fatty acid biosynthesis, making it a key drug target.
  • Understanding saFabI's mechanism is critical for developing effective inhibitors.

Purpose of the Study:

  • To elucidate the mechanism of ligand and inhibitor binding to saFabI.
  • To investigate the structural dynamics and conformational changes of saFabI.
  • To explore the role of saFabI in reducing branched-chain fatty acid precursors.

Main Methods:

  • Structural biology techniques to capture enzyme snapshots.
  • Analysis of enzyme conformational transitions (dimer-tetramer).
  • Investigating saFabI's interaction with various ligands and inhibitors.

Main Results:

  • Detailed mechanistic insights into saFabI ligand and inhibitor binding were obtained.
  • Significant protein flexibility and a dimer-tetramer transition were observed.
  • Key differences in ligand recognition compared to homologous enzymes were identified.
  • saFabI's capacity to reduce branched-chain fatty acid precursors was confirmed.
  • Branched-chain fatty acids were shown to be essential for S. aureus membrane integrity and fitness.

Conclusions:

  • The structural flexibility of saFabI rationalizes its role in branched-chain fatty acid metabolism.
  • These findings resolve debates on the essentiality of fatty acid biosynthesis in S. aureus.
  • saFabI is validated as a promising drug target for combating MRSA infections.

More Related Videos

Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds06:36

Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds

Published on: September 8, 2021

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes07:44

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes

Published on: February 14, 2025

Related Concept Videos

Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Staphylococcal Skin Infections01:29

Staphylococcal Skin Infections

Staphylococcus aureus is a Gram-positive coccus that resides harmlessly on the skin and mucous membranes of healthy individuals. When the skin barrier is breached, it can shift from a commensal to an opportunistic pathogen. This transition is facilitated by surface adhesins, such as clumping factor B and S. aureus surface protein G (SasG), which bind to structural proteins, including loricrin and cytokeratin, in the damaged epidermis. Protein A, another key factor, binds the Fc region of...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.