Colonization resistance, i.e., the protective effects of associated microbiota for the animal host against pathogen infection, has been studied widely over the last 100 years. However, few molecules mediating colonization resistance have been identified. In the symbiosis formed by Delia antiqua and its associated microbes, six bacteria protect larvae from infection with the entomopathogen Beauveria bassiana, providing an ideal model to investigate the chemical mechanism for colonization resistance. Subsequently using this symbiotic system, we first compared effects of the six bacterial species, and one control bacterium (Klebsiella oxytoca) that showed no antifungal effects, on B. bassiana and its infection of D. antiqua. Second, metabolomic profiles of the six bacteria and K. oxytoca were compared to identify candidate metabolites that may prevent infection. Third, the concentrations of candidate metabolites in situ from axenic and nonaxenic larvae were determined. Finally, effects of artificial metabolite cocktails on B. bassiana and its infection of D. antiqua larvae were determined. Results showed that compared to K. oxytoca, the six bacteria produced a metabolite cocktail showing inhibitory effects on conidial germination, mycelial growth of B. bassiana, and fungal infection. Our work revealed novel molecules that mediate colonization resistance, which could help in developing chemical mechanisms of colonization resistance. Moreover, this work may aid in discovery and expansion of new bioactive antibiotics, promoting development of prophylactic and therapeutic approaches for treating infectious diseases.

中文翻译：

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共生细菌衍生的有机酸可保护熟成虫幼虫免受致病性真菌感染

在过去的100年中，已经广泛研究了抗定殖性，即相关微生物群对动物宿主抵抗病原体感染的保护作用。但是，几乎没有发现介导定植抗性的分子。在由Delia antiqua及其相关微生物形成的共生中，六种细菌可保护幼虫免受昆虫病原球孢白僵菌的感染，从而为研究定植抗性的化学机制提供了理想的模型。随后，使用这种共生系统，我们首先比较了这6种细菌和一种对白僵菌及其对D. antiqua的感染没有表现出抗真菌作用的对照细菌（克雷伯菌oxytoca）的影响。。其次，比较了六种细菌和催产克氏杆菌的代谢组学特征，以鉴定可能预防感染的候选代谢产物。三，候选人代谢物的浓度在原位从无菌和nonaxenic幼虫进行了测定。最后，对人工代谢鸡尾酒效应B. 白僵菌和其感染D.蝇确定幼虫。结果表明，相对于催娩克氏，六个细菌产生表示对孢子萌发，菌丝生长抑制效应的代谢物鸡尾酒B. 白僵菌和真菌感染。我们的工作揭示了介导定植抗性的新型分子，这可能有助于发展定植抗性的化学机制。此外，这项工作可能有助于发现和扩展新的生物活性抗生素，促进治疗传染病的预防和治疗方法的发展。