Microbial communities such as those residing in the human gut are highly diverse and complex,and many with important implications for health and diseases.The effects and functions of these microbial communities are de...Microbial communities such as those residing in the human gut are highly diverse and complex,and many with important implications for health and diseases.The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra-and inter-cellular states at the transcriptional level.Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed.Here we report the development and utilization of a droplet-based smRNA-seq(single-microbe RNA sequencing)method capable of identifying large species varieties in human samples,which we name smRandom-seq2.Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples,we established a single-cell level bacterial transcriptional landscape of human gut microbiome,which included 29,742 single microbes and 329 unique species.Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered.Additionally,we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome.Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.展开更多
目的研究自医院污水中分离的宽噬噬菌体,治疗小鼠产超广谱β-内酰胺酶(ESBLs)大肠埃希菌感染的疗效。方法从医院污水中分离筛选出宽噬噬菌体,建立小鼠全身感染模型,观察宽噬噬菌体治疗小鼠的细菌感染的疗效。结果细菌感染的小鼠立即腹...目的研究自医院污水中分离的宽噬噬菌体,治疗小鼠产超广谱β-内酰胺酶(ESBLs)大肠埃希菌感染的疗效。方法从医院污水中分离筛选出宽噬噬菌体,建立小鼠全身感染模型,观察宽噬噬菌体治疗小鼠的细菌感染的疗效。结果细菌感染的小鼠立即腹腔注射纯化的Φ9882(MOI≥10-4,multiple of infection,感染复数),小鼠生存率为100%;Φ9882(MOI,200)延迟1 h治疗感染的小鼠仍有60%的生存率;热失活Φ9882治疗感染的小鼠生存率为0。结论通过噬菌体治疗剂量、延迟治疗、热失活、体内分布和免疫反应方面的研究,宽噬噬菌体Φ9882能有效地治疗小鼠产ESBLs大肠埃希菌感染,无不良副作用,从而为进一步应用噬菌体进行临床抗感染治疗奠定基础。展开更多
基金supported by the National Natural Science Foundation of China(No.32200073 and 32250710678,Y.W.)Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2021R01012,Y.W.)+1 种基金“Pioneer”R&D programs of Zhejiang Province(No.2024C03005,Y.W.)Key R&D Program of Zhejiang(No.2024SSYS0022,Y.W.).
文摘Microbial communities such as those residing in the human gut are highly diverse and complex,and many with important implications for health and diseases.The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra-and inter-cellular states at the transcriptional level.Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed.Here we report the development and utilization of a droplet-based smRNA-seq(single-microbe RNA sequencing)method capable of identifying large species varieties in human samples,which we name smRandom-seq2.Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples,we established a single-cell level bacterial transcriptional landscape of human gut microbiome,which included 29,742 single microbes and 329 unique species.Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered.Additionally,we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome.Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
文摘目的研究自医院污水中分离的宽噬噬菌体,治疗小鼠产超广谱β-内酰胺酶(ESBLs)大肠埃希菌感染的疗效。方法从医院污水中分离筛选出宽噬噬菌体,建立小鼠全身感染模型,观察宽噬噬菌体治疗小鼠的细菌感染的疗效。结果细菌感染的小鼠立即腹腔注射纯化的Φ9882(MOI≥10-4,multiple of infection,感染复数),小鼠生存率为100%;Φ9882(MOI,200)延迟1 h治疗感染的小鼠仍有60%的生存率;热失活Φ9882治疗感染的小鼠生存率为0。结论通过噬菌体治疗剂量、延迟治疗、热失活、体内分布和免疫反应方面的研究,宽噬噬菌体Φ9882能有效地治疗小鼠产ESBLs大肠埃希菌感染,无不良副作用,从而为进一步应用噬菌体进行临床抗感染治疗奠定基础。
