PNAS:中科院植生所王四宝研究组发现病原真菌招募肠道微生物促
2017年5月22日，国际著名学术期刊《美国科学院院刊》在线发表了中国科学院上海植物生理生态研究所王四宝研究组题为“Insect pathogenic fungus interacts with the gut microbiota to accelerate mosquito mortality”的研究论文。研究揭示了病原真菌利用肠道微生物加速杀蚊的新机制。硕博连读生魏舸、助理研究员赖屹玲和硕博连读生王官栋是论文的并列第一作者，王四宝研究员为通讯作者。
蚊虫传播多种疾病，严重威胁人类的生命健康。蚊虫控制是阻断蚊媒传染病的重要措施。病原真菌通过昆虫体壁侵染，在蚊虫生物防治和阻断疾病传播上具有巨大优势，被认为是下一代最有潜力的生物杀蚊剂之一。病原真菌在与宿主昆虫进攻与防御的军备竞赛中进化出多种致病因子和毒素，成为真菌战胜昆虫的有力“武器”。近年来研究表明，肠道微生物在调节宿主免疫稳态和影响疟原虫等肠道病原物的侵染中发挥重要作用，对宿主的健康和病原感染产生重要的影响。
研究发现肠道微生物在病原真菌杀蚊过程中起着重要的促进作用，成为真菌杀蚊的“帮凶”。当真菌通过蚊虫体壁侵染后，肠道细菌数量显著增多，造成按蚊肠道菌群失衡，条件致病菌(宿主免疫缺陷时才致病的细菌)大量增殖，将其回接至无菌按蚊肠道显著加速真菌杀蚊。肠道菌群深度测序证实，真菌体壁侵染后，肠道菌群多样性指数显著降低，一些有益肠道菌的丰度显著下降或消失，条件致病菌丰度显著增加，优势菌群发生易位。随后，过度增殖的条件致病菌(如沙雷氏菌)突破肠道屏障，转移到蚊虫血腔，造成系统性感染，从而加速蚊虫死亡。进一步研究揭示真菌侵染后显著抑制肠道双氧化酶和抗菌肽的表达，造成肠道免疫失调，进而导致肠道菌群紊乱。该研究揭示了体壁入侵的病原真菌通过招募肠道细菌促进杀虫的新机制，为理解肠道微生物的作用和病原真菌致病机理提供新视角，为发展新型蚊虫生防制剂提供新的思路。
病原真菌与肠道细菌在协同杀蚊中的互作模式：真菌通过分泌毒素等抑制按蚊肠道免疫，导致肠道菌群失衡，条件致病菌大量增殖并转移至昆虫血腔，引起系统性感染，从而加速蚊虫死亡。
原文链接：
Insect pathogenic fungus interacts with the gut microbiota to accelerate mosquito mortality
原文摘要：
The insect gut microbiota plays crucial roles in modulating the interactions between the host and intestinal pathogens. Unlike viruses, bacteria, and parasites, which need to be ingested to cause disease, entomopathogenic fungi infect insects through the cuticle and proliferate in the hemolymph. However, interactions between the gut microbiota and entomopathogenic fungi are unknown. Here we show that the pathogenic fungus Beauveria bassiana interacts with the gut microbiota to accelerate mosquito death. After topical fungal infection, mosquitoes with gut microbiota die significantly faster than mosquitoes without microbiota. Furthermore, fungal infection causes dysbiosis of mosquito gut microbiota with a significant increase in gut bacterial load and a significant decrease in bacterial diversity. In particular, the opportunistic pathogenic bacterium Serratia marcescens overgrows in the midgut and translocates to the hemocoel, which promotes fungal killing of mosquitoes. We further reveal that fungal infection down-regulates antimicrobial peptide and dual oxidase expression in the midgut. Duox down-regulation in the midgut is mediated by secretion of the toxin oosporein from B. bassiana. Our findings reveal the important contribution of the gut microbiota in B. bassiana-killing activity, providing new insights into the mechanisms of fungal pathogenesis in insects.
作者：王四宝
