Department of Biology, Barnard College, New York, New York, USA.
Microbiol Spectr. 2024 Feb 6;12(2):e0334923. doi: 10.1128/spectrum.03349-23. Epub 2024 Jan 5.
Microsporidia cause disease in many beneficial insects, including honey bees, yet few pathogen control tools are available for protecting these important organisms against infection. Some evidence suggests that microsporidia possess a reduced number of genes encoding DNA repair proteins. We hypothesized that microsporidia would thus be susceptible to treatment with DNA-damaging agents and tested this hypothesis using a novel, rapid method for achieving robust and homogenous experimental infection of large numbers of newly emerged honey bees with one of its microsporidia pathogens, () . In carrying out these experiments, we found this novel inoculation method to have similar efficacy as other traditional methods. We show that the DNA-damaging agent bleomycin reduces levels, with minimal but measurable effects on honey bee survival and increased expression of midgut cellular stress genes, including those encoding SHSP. Increased expression of suggests the occurrence of epithelial regeneration, which may contribute to host resistance to bleomycin treatment. While bleomycin does reduce infection levels, host toxicity issues may preclude its use in the field. However, with further work, bleomycin may provide a useful tool in the research setting as a potential selection agent for genetic modification of microsporidia.IMPORTANCEMicrosporidia cause disease in many beneficial insects, yet there are few tools available for control in the field or laboratory. Based on the reported paucity of DNA repair enzymes found in microsporidia genomes, we hypothesized that these obligate intracellular parasites would be sensitive to DNA damage. In support of this, we observed that the well-characterized DNA damage agent bleomycin can reduce levels of the microsporidia () in experimental infections in honey bees. Observation of slightly reduced honey bee survival and evidence of sublethal toxicity likely preclude the use of bleomycin in the field. However, this work identifies bleomycin as a compound that merits further exploration for use in research laboratories as a potential selection agent for generating genetically modified microsporidia.
微孢子虫可引起包括蜜蜂在内的许多有益昆虫患病,但目前用于保护这些重要生物免受感染的病原体控制工具很少。有证据表明,微孢子虫编码 DNA 修复蛋白的基因数量较少。我们假设微孢子虫因此容易受到 DNA 损伤剂的治疗,并用一种新的、快速的方法来验证这一假设,这种方法可以有效地使大量新出现的蜜蜂受到一种微孢子虫病原体()的均匀感染。在进行这些实验时,我们发现这种新的接种方法与其他传统方法具有相似的功效。我们表明,DNA 损伤剂博莱霉素可降低水平,对蜜蜂的生存能力有最小但可测量的影响,并增加了中肠细胞应激基因的表达,包括那些编码热休克蛋白的基因。表达增加表明上皮细胞再生的发生,这可能有助于宿主抵抗博莱霉素的治疗。虽然博莱霉素确实降低了感染水平,但宿主毒性问题可能会排除其在野外的使用。然而,通过进一步的工作,博莱霉素可能会在研究环境中提供一种有用的工具,作为遗传修饰微孢子虫的潜在选择剂。
微孢子虫可引起许多有益昆虫患病,但目前在田间或实验室中控制这种疾病的工具很少。基于微孢子虫基因组中发现的 DNA 修复酶的缺乏,我们假设这些专性细胞内寄生虫对 DNA 损伤敏感。支持这一观点的是,我们观察到,在实验感染蜜蜂中,特征良好的 DNA 损伤剂博莱霉素可以降低微孢子虫的水平。观察到蜜蜂存活率略有降低和亚致死毒性的证据,可能排除了博莱霉素在野外的使用。然而,这项工作确定博莱霉素是一种值得进一步探索的化合物,可作为研究实验室中潜在的选择剂,用于生成遗传修饰的微孢子虫。