The Inhibitory Effect of combined human cathelicidin with antibiotics on antibiotic-resistant Cutibacterium acnes

Abstract

Cutibacterium acnes is one of the major factors involved in the pathogenesis of acne vulgaris which sometimes develops antibiotic resistance particularly clindamycin- and doxycycline-resistant C. acnes. In this study, human cathelicidin (LL-37) which is a type of human antimicrobial peptide against a wide range of microorganisms was used. We investigated the antimicrobial activity of LL-37 on C. acnes isolated from patients with acne at the King Chulalongkorn Hospital using broth microdilution. Moreover, the synergistic effects of LL-37 with clindamycin and doxycycline were investigated using checkerboard microdilution, and time-killing assays. The cytotoxicity of LL-37 was also evaluated by MTT assay. The results demonstrated that LL-37 had an inhibitory effect against all clinical isolates of a C. acnes including antibiotic-resistant strain at concentrations ranging from 25 to 50 µg/ml. Furthermore, LL-37 at the concentration of 0.1µg/ml showed a synergistic effect with doxycycline at the concentration of 8 µg/ml with the fractional inhibitory concentration index (FICI) of 0.50. However, the combination of LL-37 and doxycycline showed a significant cytotoxic effect on human keratinocytes. Therefore, better understandings how to reduce the cytotoxicity of this drug combination are required, and the synergistic effect of LL-37 with other topical antibiotics is probably needed.