In this study, we demonstrated that C. acnes kills silkworms reared at 37˚C and that the silkworm infection model can be used to evaluate the efficacy of antibacterial drugs. Our findings suggest that the silkworm infection model is useful for assessing pathogenicity and the efficacy of antimicrobial drugs against systemic infection by C. acnes.
Bacterial components such as peptidoglycans of Porphyromonas gingivalis lead to shock in silkworms, resulting in their death (24). Injection of viable or heat-killed P. gingivalis cells cause silkworm death (24). Under conditions in which shock occurs, silkworms cannot be treated with antibiotics (24). In the silkworm C. acnes infection model established in this study, administration of heat-killed bacteria did not kill the silkworm. Further, C. acnes-infected silkworms could be effectively treated with antibacterial drugs, suggesting that the growth of C. acnes in the body of silkworms is important for its pathogenicity. Silkworm infection models are useful for identifying virulence factors of pathogenic microorganisms (13) (14). Further studies are needed to determine which factors in C. acnes are responsible for the pathogenicity to silkworms.
The pharmacokinetics of antimicrobial agents are similar between silkworms and mammals, and antimicrobial drug efficacy in the silkworm infection model can be evaluated on the basis of the pharmacokinetics (21, 25–27). Therefore, silkworm infection models are useful for the development for in vivo screening of new antimicrobial agents (20, 22). The silkworm C. acnes infection model with may be useful for identifying effective antibacterial compounds against systemic infection by C. acnes. Azole antifungals exhibit antimicrobial activity against C. acnes in vitro, and ketoconazole inhibits the lipase activity of C. acnes (28, 29). Further studies are needed to identify effective compounds against systemic C. acnes infections from among clinically applied drugs using the silkworm infection model.
Recently, an infection model with C. acnes using a nematode, Caenorhabditis elegans, was reported (30). C. elegans is useful for identifying host factors against C. acnes infection based on genetic approaches (30). The differences between the silkworm system and the C. elegans system are that the silkworm blood can be directly injected with C. acnes and its pathogenicity at 37˚C, the same temperature as the human body, can be verified. C. elegans is difficult to inject quantitatively into body fluids and cannot grow at 37˚C (31). The silkworm infection model might allow us to identify virulence factors of C. acnes at the body temperature of humans.
In conclusion, we established a silkworm infection model with C. acnes and found the system to be useful for evaluating antibacterial drug efficacy. Further studies are needed to determine the clinical applicability of research using the silkworm C. acnes infection model.
The results of this study are limited to one strain and only a few antibacterial drugs. Further in vivo studies for chemical screening are required to clarify whether the silkworm infection model could be effective for identifying candidate compounds.