Evaluation of Antibacterial Drugs Using Silkworms Infected by Cutibacterium acnes.

Yasuhiko Matsumoto,Yuki Tateyama,Takashi Sugita

doi:10.3390/insects12070619

Abstract

Simple SummaryCutibacterium acnes, a common bacterium on human skin, is a causative agent of inflammatory skin diseases and systemic infections. Systemic infections caused by C. acnes are difficult to treat because of the drug resistance to typical macrolides. The development of a systemic infection model for C. acnes contributes to searching candidates for drug discovery. Silkworm is a useful model animal for evaluating the efficacy of compounds. Several silkworm infection models have been established for the identification of virulence-related genes and novel antibacterial drugs. However, the systemic infection model of C. acnes using silkworms was not yet established. We established a new silkworm infection model with C. acnes and evaluated the efficacy of antibacterial drugs using the silkworm infection model. The silkworm infection model might be used to identify drug candidates for the treatment against C. acnes infection.Cutibacterium acnes is a causative agent of inflammatory skin diseases and systemic infections. Systemic infections caused by C. acnes are difficult to treat, and the development of a systemic infection model for C. acnes would be useful for elucidating the mechanisms of infection and searching for therapeutic agents. In this study, we established a silkworm infection model as a new experimental system to evaluate the interaction between C. acnes and the host, and the efficacy of antibacterial drugs. Silkworms infected with C. acnes died when reared at 37 °C. The dose of injected bacterial cells required to kill half of the silkworms (LD50) was determined under rearing conditions at 37 °C. The viable cell number of C. acnes was increased in the hemolymph and fat body of the infected silkworms. Silkworms injected with autoclaved C. acnes cells did not die during the study period. The survival time of silkworms injected with C. acnes was prolonged by the injection of antibacterial drugs such as tetracycline and clindamycin. These findings suggest that the silkworm C. acnes infection model can be used to evaluate host toxicity caused by C. acnes and the in vivo efficacy of antimicrobial drugs.

Highlights

Cutibacterium acnes, a common bacterium on human skin, causes inflammatory skin diseases and systemic infections [1,2]
Silkworms injected with C. acnes (1.6 × 109 cells) reared at 37 ◦ C after injection died within 40 h, whereas infected silkworms reared at 32 ◦ C survived longer (Figure 1)
These results suggest that rearing C. acnes-infected silkworms at 37 ◦ C decreased survival and that the pathogenicity of C. acnes can be quantitatively assessed based on the LD50 value

Summary

Introduction

Cutibacterium acnes (formerly Propionibacterium acnes), a common bacterium on human skin, causes inflammatory skin diseases and systemic infections [1,2]. Biofilm formation by C. acnes on implants and intervertebral discs causes bloodstream infections [5,6,7]. Because C. acnes forms a biofilm and more than 50% of clinically isolated C. acnes are resistant to typical macrolides, systemic infections caused by C. acnes are difficult to treat [8,9]. The development of treatments for systemic infections caused by C. acnes is clinically important. Infection experiments using a large number of mammalian animals are difficult to perform due to animal welfare issues [12]

Methods

Results

Conclusion