novobiocin

Novobiocin is an aminocoumarin antibiotic produced by certain Streptomyces species, notably Streptomyces spheroides. It is a natural product that has been used historically as an antibacterial agent and as a research tool in molecular biology.

Mechanism of action: Novobiocin inhibits bacterial DNA gyrase by binding to the GyrB subunit, blocking ATPase activity and preventing the ATP-dependent supercoiling of DNA required for replication. As a result, the drug is generally considered bacteriostatic rather than bactericidal.

Spectrum and clinical use: The antibiotic shows activity primarily against Gram-positive bacteria, including Staphylococcus aureus and various Streptococcus species. Its activity against Gram-negative bacteria is limited due to permeability barriers. Because of toxicity concerns and the rise of resistance, novobiocin is no longer a first-line systemic antibiotic in most clinical settings and has largely been superseded by fluoroquinolones. It remains of historical, research, and some niche veterinary relevance, and is used in laboratory applications.

Resistance: Resistance commonly arises from mutations in the gyrB gene encoding the gyrase B subunit, reducing binding of novobiocin. Additional mechanisms include decreased drug uptake and active efflux.

Laboratory use: In laboratory settings, novobiocin resistance is used as a selectable marker in certain plasmid systems, enabling researchers to select for cells carrying the resistance determinant on growth media containing the drug.

Chemistry: Novobiocin belongs to the aminocoumarin class of antibiotics and features a coumarin lactone core with an amine-containing side chain.