Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic microorganisms

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.

FIG. 1.

Therapeutic effects of antibiotics in silkworms infected with S. aureus (A) or S. maltophilia (B). Data are representative of one of two identical experiments.

FIG. 2.

Therapeutic effects of antifungal drugs in silkworms infected with the true fungus C. tropicalis (A) or C. albicans (B). Data are representative of one of two identical experiments.

FIG. 3.

Therapeutic effects of antibiotics administered i.m. (A) or p.o. (B) on silkworms infected with S. aureus.

FIG. 4.

Transport of chloramphenicol and vancomycin from the midgut to the hemolymph in living silkworms. All data points are averages of duplicate samples.

FIG. 5.

Transport of antibiotics from isolated midguts. (A) Time course of transport with 1 mM chloramphenicol or vancomycin. (B) Transport of chloramphenicol and vancomycin at various concentrations for 30 min. All data points are averages of duplicate samples.