bafilomycins

Bafilomycins are a family of macrolide antibiotics produced by soil-dwelling actinomycetes, notably Streptomyces species. The prototypical member, bafilomycin A1, is accompanied by several related congeners (A2, B1, B2, C1, C2). All share a 16-membered macrolide lactone core and differ in side-chain substitutions.

They act as potent inhibitors of vacuolar-type H+-ATPases (V-ATPases), proton pumps responsible for acidifying intracellular compartments such as lysosomes, endosomes, and the Golgi apparatus. Inhibition of V-ATPases raises organellar pH, inhibiting lysosomal degradation, endocytic trafficking, and autophagy. Because of their mechanism and cytotoxic effects, bafilomycins are primarily used as laboratory tools rather than clinical antibiotics.

In research, bafilomycin A1 is the most commonly used compound, employed to study autophagy, lysosome function, and vesicular trafficking in a wide range of eukaryotic cells. Potency is typically in the nanomolar range, with suggested selectivity for V-ATPases over other ATPases, though off-target effects and toxicity in whole organisms limit broader applications.

Bafilomycins are natural products produced by Streptomyces and related actinomycetes; they are typically accessed via fermentation and isolation from microbial cultures, with structural variants obtained by isolation from different strains or by semisynthesis.

Safety and handling: due to their potent effects on cellular homeostasis, bafilomycins can be cytotoxic to mammalian cells; appropriate laboratory containment and safety practices are required.