Wax moth larva (Galleria mellonella): an in vivo model for assessing the efficacy of antistaphylococcal agents

被引:164
作者
Desbois, Andrew P. [1 ]
Coote, Peter J. [1 ]
机构
[1] Univ St Andrews, Sch Biol, St Andrews KY16 9ST, Fife, Scotland
关键词
antibacterial; antimicrobial; daptomycin; drug discovery; drug resistance; insect infection model; MRSA; Staphylococcus aureus; vancomycin; ALTERNATIVE INFECTION MODEL; STAPHYLOCOCCUS-AUREUS MRSA; RESISTANT; VIRULENCE; ANTIBACTERIAL; PATHOGENESIS; EXPRESSION; SYSTEM;
D O I
10.1093/jac/dkr198
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: To investigate whether the wax moth larva, Galleria mellonella, is a suitable host for assessing the in vivo efficacy of antistaphylococcal agents against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) infections. Methods: Wax moth larvae were infected with increasing doses of S. aureus to investigate the effect of inoculum size on larval survival. In addition, infected wax moth larvae were treated with daptomycin, penicillin or vancomycin to examine whether these agents were effective against S. aureus and MRSA infections in vivo. Results: Increasing inoculum doses of live S. aureus cells resulted in greater larval mortality, but heat-killed bacteria and cell-free culture filtrates had no detrimental effects on survival. Larval mortality rate also depended on the post-inoculation incubation temperature. After larvae were infected with S. aureus, larval survival was enhanced by administering the antistaphylococcal antibiotics daptomycin or vancomycin. Larval survival increased with increasing doses of the antibiotics. Moreover, penicillin improved survival of larvae infected with a penicillin-susceptible methicillin-susceptible S. aureus (MSSA) strain, but it was ineffective at similar doses in larvae infected with MRSA (penicillin resistant). Daptomycin and vancomycin were also effective when administered to the larvae prior to infection with bacteria. Conclusions: This is the first report to demonstrate that antibiotics are effective in the wax moth larva model for the treatment of infections caused by Gram-positive bacteria. The new wax moth larva model is a useful preliminary model for assessing the in vivo efficacy of candidate antistaphylococcal agents before proceeding to mammalian studies, which may reduce animal experimentation and expense.
引用
收藏
页码:1785 / 1790
页数:6
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