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Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic
Hiroshi Hamamoto1, Kenji Kurokawa, Chikara Kaito
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
The injection of bacteria (Staphylococcus aureus, Stenotrophomonas maltophilia) or true fungi (Candida albicans, Candida tropicalis) that are pathogenic to humans into the silkworm hemolymph leads to death of the larvae within 2 days. Antibiotics used for clinical purposes have therapeutic effects on silkworms infected with these pathogens. The 50% effective doses obtained by injection into the silkworm hemolymph are consistent with those reported for mice. Injection of vancomycin and kanamycin into the silkworm hemolymph was effective, but oral administration was not. Chloramphenicol, which is effective by oral administration, appeared in the silkworm hemolymph soon after injection into the midgut, whereas vancomycin did not. Isolated midgut membranes were impermeable to vancomycin. Thus, the ineffectiveness of oral administration of vancomycin to silkworms is due to a lack of intestinal absorption.
Insights
Silkworms are a viable model for testing antibiotic efficacy against human pathogens like Staphylococcus aureus. Oral vancomycin is ineffective in silkworms due to poor intestinal absorption, unlike injection.
Area of Science:
- Microbiology
- Pharmacology
- Insect models
Background:
- Silkworms (Bombyx mori) are susceptible to human pathogenic bacteria and fungi.
- Clinical antibiotics demonstrate therapeutic effects in silkworm infection models.
- Silkworm models offer a cost-effective alternative for preliminary drug efficacy studies.
Purpose of the Study:
- To evaluate the efficacy of clinical antibiotics against microbial infections in silkworms.
- To investigate the pharmacokinetic differences between injected and orally administered antibiotics in silkworms.
- To determine the suitability of silkworms as a model organism for antibiotic drug development.
Main Methods:
- Silkworms were injected with pathogenic bacteria (Staphylococcus aureus, Stenotrophomonas maltophilia) and fungi (Candida albicans, Candida tropicalis).
- Antibiotic efficacy was assessed by observing larval survival rates and calculating 50% effective doses (ED50).
- Antibiotic presence in hemolymph was measured after injection and oral administration, with midgut membrane permeability assessed.
Main Results:
- Bacterial and fungal infections were lethal to silkworms within 48 hours.
- Injected vancomycin and kanamycin showed efficacy, with ED50 values comparable to mouse models.
- Oral vancomycin was ineffective, correlating with its inability to permeate isolated midgut membranes, indicating poor intestinal absorption.
Conclusions:
- Silkworms serve as a relevant in vivo model for assessing antibiotic effectiveness against human pathogens.
- The route of administration significantly impacts antibiotic efficacy in silkworms, particularly for drugs with poor oral bioavailability.
- Vancomycin's oral ineffectiveness in silkworms is attributed to a lack of intestinal absorption, highlighting the importance of this factor in drug efficacy.
