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

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.

Whole-genome sequencing, annotation, and biological characterization of a novel Siphoviridae phage against multi-drug resistant Propionibacterium acne

“…Phages can treat bacterial infections regardless of antibiotics-resistance ( Yin et al, 2017 ; Yang et al, 2019a ). There were reports on P. acne phage effectively treating multi-drug-resistant P. acne -induced acne vulgaris in animal experiments ( Lam et al, 2021 ) and clinical trials ( Golembo et al, 2022 ), indicating potential clinical values. However, phage therapy for treating severe acne vulgaris induced by antibiotic-resistant P. acne is insufficient.…”

Towards phage therapy for acne vulgaris: Topical application in a mouse model

“…Previous studies have assessed the activity and efficacy of injected acne phages in an acne mouse model (Kim et al, 2019; Lam et al, 2021; Nelson et al, 2012). Such a method of phage delivery is not clinically applicable.…”

“…The first C. acnes phage was isolated in 1964 by Brzin (BRZIN, 1964), but only in recent years has phage therapy become a potential treatment approach for acne vulgaris, as reflected by the increase in academic and industrial performance publications. Nevertheless, research on this topic is lacking, as in vivo phage therapy in an acne mouse model has been tested only by intralesional injections of C. acnes phages, and the efficacy of topical application, has not yet been shown (Kim et al, 2019; Lam et al, 2021; Nelson et al, 2012).…”

The immunomodulatory potential of phage therapy to treat acne: a review on bacterial lysis and immunomodulation

“…Moreover, a reduction of inflammatory markers, such as neutrophils, IL-1β, MMP-3, MMP-9 and CD8+ T cells ( Kim et al, 2019 ), related to acne pathogenesis was observed in phage treated animals. More recently, Lam et al (2021) carried out similar experiments to assess the therapeutic effect of a C. acnes phage. In this study, C. acnes was also inoculated on mice skin and reduction of lesions was evaluated post-mortem .…”

“…Reduced inflammation of the lesions was observed and confirmed by histological findings. IL-1β expression in inoculated skin was reduced by phage therapy, along with the apoptosis marker Caspase-3 ( Lam et al, 2021 ). These studies show that C. acnes phages can have anti-inflammatory properties.…”