ArticleThe Journal of biological chemistry2012
Mechanism of elongation factor-G-mediated fusidic acid resistance and fitness compensation in Staphylococcus aureus.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
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- Intermittent antibiotic exposure of Escherichia coli biofilms drives resistance in catheter-associated infection models.NPJ biofilms and microbiomes · 2026Article
- High-yield porphyrin production through metabolic engineering and biocatalysis.Nature biotechnology · 2025Article
- Mechanisms of fusidic acid resistance.Biochemical Society transactions · 2025Review
- Collateral sensitivity and cross-resistance in six species of bacteria exposed to six classes of antibiotics.Microbiology spectrum · 2025Article
- Comprehensive genome analysis ofVeterinary world · 2025Article
- Structures of the Staphylococcus aureus ribosome inhibited by fusidic acid and fusidic acid cyclopentane.Scientific reports · 2024Article
- Recent Advancement in Novel Wound Healing Therapies by Using Antimicrobial Peptides Derived from Humans and Amphibians.Current protein & peptide science · 2024Review
- Topical Antibiotic Treatment in Dermatology.Antibiotics (Basel, Switzerland) · 2023Review
- Article
- The Quorum-Sensing Inhibitor Furanone C-30 Rapidly Loses Its Tobramycin-Potentiating Activity against Pseudomonas aeruginosa Biofilms during Experimental Evolution.Antimicrobial agents and chemotherapy · 2021Article
- Structural basis of elongation factor 2 switching.Current research in structural biology · 2020Article
- Phenotypic Modulation of Biofilm Formation in aFrontiers in microbiology · 2020Article
- Discovery of Furanoquinone Derivatives as a Novel Class of DNA Polymerase and Gyrase Inhibitors for MRSA Eradication in Cutaneous Infection.Frontiers in microbiology · 2019Article
- Complementary charge-based interaction between the ribosomal-stalk protein L7/12 and IF2 is the key to rapid subunit association.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Crystal structure of a Pseudomonas malonate decarboxylase holoenzyme hetero-tetramer.Nature communications · 2017Article
- Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.Clinical microbiology reviews · 2017Review
- Fusidic Acid: A Bacterial Elongation Factor Inhibitor for the Oral Treatment of Acute and Chronic Staphylococcal Infections.Cold Spring Harbor perspectives in medicine · 2016Review
- HflX is a ribosome-splitting factor rescuing stalled ribosomes under stress conditions.Nature structural & molecular biology · 2015Article
- A conserved histidine in switch-II of EF-G moderates release of inorganic phosphate.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibiotic resistance in bacteria is often associated with fitness loss, which is compensated by secondary mutations. Fusidic acid (FA), an antibiotic used against pathogenic bacteria Staphylococcus aureus, locks elongation factor-G (EF-G) to the ribosome after GTP hydrolysis. To clarify the mechanism of fitness loss and compensation in relation to FA resistance, we have characterized three S. aureus EF-G mutants with fast kinetics and crystal structures. Our results show that a significantly slower tRNA translocation and ribosome recycling, plus increased peptidyl-tRNA drop-off, are the causes for fitness defects of the primary FA-resistant mutant F88L. The double mutant F88L/M16I is three to four times faster than F88L in both reactions and showed no tRNA drop-off, explaining its fitness compensatory phenotype. The M16I mutation alone showed hypersensitivity to FA, higher activity, and somewhat increased affinity to GTP. The crystal structures demonstrate that Phe-88 in switch II is a key residue for FA locking and also for triggering interdomain movements in EF-G essential for its function, explaining functional deficiencies in F88L. The mutation M16I loosens the hydrophobic core in the G domain and affects domain I to domain II contact, resulting in improved activity both in the wild-type and F88L background. Thus, FA-resistant EF-G mutations causing fitness loss and compensation operate by affecting the conformational dynamics of EF-G on the ribosome.
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