INABILITY OF A BACTERIAL LIPASE INHIBITOR TO CONTROL ACNE-VULGARIS

[摘要] The pathogenesis of acne is generally belived to involve the generation of fatty acids from sebum lipids by bacterial lipases. Following purification and characterization of these lipases a systematic study of inhibitors was undertaken. The class of halopyridyl phosphorus compounds, such as o,o-dimethyl-o-(3,5,6 trichloro-2-pyridyl) phosphate, fospirate, were potent inhibitors in vitro at concentrations as low as 10-8 M. These compounds are so potent that the topical application of 1 dose of fospirate (3 mg/100 cm2 of facial skin) suppressed the fatty acids 40% within the initial 12 h of exposure. This is comparable to the suppression induced by 1 mo. of systemic tetracycline. To study the effect of fospirate on acne vulgaris, 10 patients with Grade II-III disease were studied over 8 wk. The patients were treated for 3 wk with vehicle only to determine baseline values and then for 5 wk with twice daily applications for fospirate. Although the fatty acids were decreased dramatically in all patients, bacterial counts and lesion counts remained unchanged. The clinical severity of the acne remained unchanged. The generation of fatty acids by bacterial lipases is apparently unrelated to the pathogenesis of acne and the bacteria may not be dependent on lipases for energy requirements. A reevaluation of the role of fatty acids in the pathogenesis of acne is needed.