Two propionibacteria identified as Propionibacterium acnes and Propionibacterium granulosum were grown anaerobically in the presence of growth subinhibitory concentrations (0.25 and 0.5 minimal inhibitory concentrations) of clindamycin, erythromycin, lincomycin, and tetracycline. Viable counts and assays of extracellular lipase were performed on samples taken at 24-h intervals over a 96-h period. The results showed that lincomycin and clindamycin could inhibit the production of the enzyme by both strains with little effect on their growth rates. Tetracycline caused inhibition of lipase production by P. granulosum only. Although production of the enzyme by P. acnes was delayed in the presence of tetracycline, the final titer was the same as the control. Erythromycin had little effect on growth and enzyme production of either strain. It is possible, therefore, that certain antibiotics used in acne therapy may act not only as bactericidal agents but also as inhibitors of enzyme production under non-growth-limiting conditions. Hydrolysis of sebum triglycerides by bacterial lipases, in particular those of propionibacteria (13,20), and the subsequent release of irritating free fatty acids in the pilosebaceous follicles has been proposed as a major factor in the formation of lesions in acne vulgaris (22). Improvement in acne is often achieved by long-term administration of broad-spectrum antibiotics which are thought to decrease the density of propionibacteria (1,12,14) and hence reduce the free fatty acids in the sebum (7, 18). At present, there are few reports describing the effects of antibiotics on propionibacteria in vitro, those that do exist being mainly concerned with the evaluation of antimicrobial susceptibility (9,19). In a recent publication, however, Webster et al. (26) found that lipase production in vitro by a strain of Propionibacterium acnes was inhibited by subgrowth-inhibitory concentrations of tetracycline and declomycin and delayed by erythromycin. The present study sought, therefore, to investigate the effect of antibiotics, commonly used in acne therapy, at subinhibitory concentrations on the growth and extracellular lipase production of P. acnes and Propionibacterium granulosum. Levels of drug at one-half and one-fourth minimal inhibitory concentrations (MIC) were chosen for this study. A similar experimental system has been used to follow the biosynthesis of toxins and enzymes in Staphylococcus aureus (5) and Streptococcus pyogenes (4).
MATERIALS AND METHODSBacteral strains. Two strains (P2 and P27) were selected from a collection of 52 Propionibacterium strains which had been isolated from normal skin and maintained anaerobically on Brewer's agar without indicator (Difco Laboratories, Detroit, Mich.), supplemented with 1% Tween 80 (Koch Light, Ltd., Colnbrook, England). The strains were identified using the biochemical classification scheme of Marples and McGinley (15): strain P2 was classified as P. acnes, and strain P27 was classified as P. granulosum.Antibiotics. The antibiotics used in thi...