Appendix_Fig S9.zip

Host defense against many Gram-positive bacteria and fungal pathogens is mainly provided by the Toll-dependent systemic immune response in Drosophila. While antimicrobial peptides active against these categories of pathogens contribute only modestly to protection, Bomanin peptides are major effectors of the Toll pathway. Remarkably, flies deleted for the 55C locus that contains 10 Bomanin genes are as sensitive as Toll pathway mutant flies to these infections. Yet, the exact functions of single Bomanins in resistance or resilience to infections remain poorly characterized. Here, we have extensively studied the role of these Bomanin genes. BomT1 functions in resistance to Enterococcus faecalis while playing a role in resilience against Metarhizium robertsii infection, like BomS2. BomT1 and BomT2 can prevent the dissemination of Candida albicans throughout the host, even though they are not sufficient to confer protection to immunodeficient flies against this pathogen in survival experiments. Furthermore, BomT1 and BomBc1 mutants are sensitive to an Aspergillus fumigatus ribotoxin. We conclude that 55C Bomanins have defined albeit sometimes overlapping roles in the different facets of host defense against infections.

在果蝇（Drosophila）中，宿主抵御多数革兰氏阳性细菌与真菌病原体的防御机制主要由Toll依赖的系统性免疫应答介导。尽管针对此类病原体的抗菌肽仅对宿主防护贡献有限，但博曼宁肽（Bomanin）却是Toll通路的核心效应分子。值得注意的是，缺失携带10个博曼宁基因的55C基因座的果蝇，在受上述病原体感染时的易感性与Toll通路突变果蝇相当。然而，单个博曼宁基因在宿主抗感染的抗性与恢复力方面的确切功能仍未得到充分阐明。本研究针对此类博曼宁基因的功能开展了系统性深入探究。与BomS2类似，BomT1不仅可介导宿主对抗粪肠球菌（Enterococcus faecalis）的感染抗性，还在宿主抵御罗伯茨绿僵菌（Metarhizium robertsii）感染的恢复过程中发挥功能。尽管BomT1与BomT2无法在生存实验中为免疫缺陷果蝇提供针对白色念珠菌（Candida albicans）的完全保护，但二者可阻止该病原体在宿主体内的系统性播散。此外，BomT1与BomBc1突变体对烟曲霉（Aspergillus fumigatus）核糖体毒素表现出易感性。综上，55C基因座编码的博曼宁蛋白在宿主抗感染防御的不同层面中，均具有明确的功能，且不同功能间有时存在重叠。