Antibacterial activities of Propionibacterium acnes bacteriophages against a diverse collection of P. acnes clinical isolates: prospects for novel alternative therapies for acne vulgaris

Abstract

A total of 136 chronically infected Canadian acne patients from Ottawa-Gatineau and Northeastern Ontario regions accounting for 75% of subjects (12-50 years old, with 90th percentile at the age of 30) who had suffered acne vulgaris (with various acne related scarring) for a median duration of 4 years, were sources for isolation of Propionibacterium acnes, the etiologic agent for acne vulgaris. Eighty-four percent of patients were subjected to various treatment regimens with topical and systemic agents including in combination with 1-3 different types of antibiotics (mean duration of 7 months). A diverse collection of 224 clinical P. acnes isolates from Canadian and Swedish subjects were characterized for their sensitivities to infection by a Canadian collection of 67 diverse phages belonging to siphoviridae; and multiple minimal cocktails consisting of 2-3 phages were formulated to be effective on global P. acnes isolates. Propionibacterium acnes isolates were characterized by multiplex PCR to belong to phylotypes IA, IB and II, which also showed resistance against commonly used antibiotics for treating acne vulgaris (overall resistance rate of 9.5%), were sensitive to phages regardless of their type and antibiotic resistance patterns, providing ground for phages as novel alternative therapeutics for future in vivo trials. The phage collection was diverse by virtue of their BamHI restriction patterns and full genome sequences and harboured a major tail protein (MTP) that appeared to be important in contributing to their host ranges. Three dimensional structural modeling of the N-domain of P. acnes MTPs implicated previously unreported involvement of the α1-β4 loop (C5 loop) within N-domain amino acid sequence in contributing to the expanded host range of a mutant phage to infect a naturally phage resistant P. acnes clinical isolate. Given the potential of phages for rapid mutational diversification surpassing that of their bacterial hosts and the fact that phages are generally regarded as safe (GRAS), rapid and cost-effective derivation of mutant phages with expanded host ranges provide a strong framework forimproving phage cocktails for use in future personalized medicine.