Antibacterial activities of Propionibacterium acnes bacteriophages against a diverse collection of P. acnes clinical isolates: prospects for novel alternative therapies for acne vulgaris
Date
2017-08-22
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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.
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Keywords
bacteriophage, phage, siphoviridae, coryneform, P acnes, acne vulgaris, antibiotic resistance, phage therapy, phylotype, clinical isolate, genome, multiplex PCR, host-range, 3D modeling, major tail protein, receptor