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Propionibacterium acnes plays an essential role in the pathogenesis of acne, and is closely associated with the inflammation in and severity of acne, which may be attributed to the structure, colonization and physiological features of this pathogen. Now, many P. acnes-targeted strategies have been developed to treat acne, including antibiotic regimens such as tetracycline, clindamycin, erythromycin, nonantibiotic regimens such as benzoyl peroxide and photodynamic therapy with ALA. With the emergence of antibiotic-resistant P. acnes, the combination of antibiotic and non-antibiotic drugs has proved to be the optimized treatment for acne. The revealment of complete genome sequence of P. acnes has made it possible for the treatment of acne with vaccines targeting P.acnes.