Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

Virulence

Andrew Balfour¹  Isabel Softley¹  Carolyn Williamson¹  Stephanie Diezmann²  Vincent M. Bruno³  Amol C. Shetty³  Heath E. O’Brien⁴  Naomi Lyons⁵ 

[1] Department of Biology & Biochemistry, University of Bath, Bath, U;Department of Biology & Biochemistry, University of Bath, Bath, U;School of Cellular and Molecular Medicine, University of Bristol, Bristol, U;Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, US;MRC Centre for Neuropsychiatric Genetics & Genomics, Division of Psychological Medicine & Clinical Neurosciences, Cardiff University, Cardiff, U;School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Tel Aviv, Israe;Department of Biology & Biochemistry, University of Bath, Bath, U;

关键词: Manduca sexta;    caterpillar;    fungal virulence;    Candida;    Cryptococcus;    Saccharomyces;    Metschnikowia;    antifungal drug;    host model;    fungal burden;   

DOI  :  10.1080/21505594.2020.1806665

来源: Taylor & Francis

【 摘 要 】

The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillar’s feces and hemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease and to facilitate host tissue-specific expression analyses. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.

【 授权许可】

CC BY