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家蚕幼虫(Galleriamellonella):评估抗葡萄球菌药物疗效的体内模型。

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

机构信息

Biomedical Sciences Research Complex, School of Biology, The North Haugh, University of St Andrews, Fife, KY16 9ST, UK.

出版信息

J Antimicrob Chemother. 2011 Aug;66(8):1785-90. doi: 10.1093/jac/dkr198. Epub 2011 May 28.

Abstract

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.

摘要

目的

研究家蚕幼虫是否适合作为评估抗葡萄球菌药物对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA)感染体内疗效的宿主。

方法

用递增剂量的金黄色葡萄球菌感染家蚕幼虫,以研究接种量大小对幼虫存活率的影响。此外,用达托霉素、青霉素或万古霉素处理感染的家蚕幼虫,以检查这些药物对金黄色葡萄球菌和 MRSA 感染的体内疗效。

结果

活金黄色葡萄球菌细胞的递增接种剂量导致更大的幼虫死亡率,但热灭活细菌和无细胞培养滤液对存活率没有不利影响。幼虫死亡率还取决于接种后孵育温度。在家蚕感染金黄色葡萄球菌后,用抗葡萄球菌抗生素达托霉素或万古霉素处理可增强幼虫的存活率。随着抗生素剂量的增加,幼虫的存活率也随之增加。此外,青霉素可提高感染青霉素敏感型耐甲氧西林金黄色葡萄球菌(MSSA)菌株的幼虫的存活率,但在感染 MRSA(青霉素耐药)的幼虫中,相同剂量的青霉素无效。在感染细菌之前,向幼虫施用达托霉素和万古霉素也有效。

结论

这是首次报道表明抗生素在家蚕幼虫模型中对治疗革兰氏阳性菌感染有效。这种新的家蚕幼虫模型是一种在进行哺乳动物研究之前评估候选抗葡萄球菌药物体内疗效的有用初步模型,这可能会减少动物实验和费用。

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