Therapeutic Effect of a Newly Isolated Lytic Bacteriophage against Multi-Drug-Resistant Cutibacterium acnes Infection in Mice

Int J Mol Sci. 2021 Jun 29;22(13):7031. doi: 10.3390/ijms22137031.

Abstract

Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.

Keywords: Cutibacterium acnes; acne vulgaris; apoptosis; bacteriophages; inflammation; phage therapy.

MeSH terms

  • Acne Vulgaris / microbiology
  • Acne Vulgaris / therapy*
  • Animals
  • Base Composition
  • Cellulose / chemistry
  • Disease Models, Animal
  • Drug Compounding
  • Drug Resistance, Multiple, Bacterial
  • Genome Size
  • Genome, Viral
  • Healthy Volunteers
  • Humans
  • Injections, Intradermal
  • Mice
  • Open Reading Frames
  • Phage Therapy / methods*
  • Phylogeny
  • Propionibacterium acnes / physiology
  • Propionibacterium acnes / virology*
  • Siphoviridae / classification*
  • Siphoviridae / genetics
  • Siphoviridae / isolation & purification
  • Skin / virology
  • Whole Genome Sequencing / methods*

Substances

  • Cellulose