DISRUPTION OF THE TRANSMEMBRANE PH GRADIENT - A POSSIBLE MECHANISM FOR THE ANTIBACTERIAL ACTION OF AZELAIC ACID IN PROPIONIBACTERIUM-ACNES AND STAPHYLOCOCCUS-EPIDERMIDIS

The effect of the topical acne treatment azelaic acid on the transmembrane proton gradient (ΔpH) of Propionibacterium acnes and Staphylococcus epidermidis was studied in vitro at external pH values found on human skin (pH 4.0-6.0). Bacteria were grown in defined media using continuous culture and ΔpH was estimated by measuring the accumulation of [14C] benzoic by the cells using flow dialysis. In both P. acnes and S. epidermidis the addition of 30 mM azelaic acid and the membrane active inhibitors nigericin (150μM) and CCCP (150μM) resulted in a rapid release of [14C] label into the dialysate indicating the dissipation of ΔpH between external pH values of 4.0-6.0. The addition of 60 mM NaCl as an iso-osmotic control and 150μm valinomycin did not induce the release of [14C] label. The addition of 30 mM azelaic acid reduced the ΔpH of P. acnes by 44% at external pH 4.0 and 28% at external pH 6.0. In S. epidermidis 30 mM azelaic acid reduced ΔpH by 88% at external pH 5.0 and 20% at external pH 6.0. Rapid loss of viability occurred in suspensions of P. acnes and S. epidermidis containing 30 mM azelaic acid at pH 4.0 with no viable cells recovered after 60min incubation. At pH 6.0 little change in viable numbers of P. acnes and S. epidermidis were observed over a 2 h incubation period. The results indicate that the antibacterial activity of azelaic acid is associated with the perturbation of intracellular pH. © 1994 The British Society for Antimicrobial Chemotherapy.