作为一种对抗真核细胞和原核细胞的强有力细菌武器,VI型分泌系统(type VI secretion system,T6SS)广泛存在于革兰氏阴性菌中。铜绿假单胞菌是一种对多种抗生素具有耐药性并能够在人体引发急性和慢性感染的条件致病菌,它编码3套独立的T6...作为一种对抗真核细胞和原核细胞的强有力细菌武器,VI型分泌系统(type VI secretion system,T6SS)广泛存在于革兰氏阴性菌中。铜绿假单胞菌是一种对多种抗生素具有耐药性并能够在人体引发急性和慢性感染的条件致病菌,它编码3套独立的T6SS,分别为H1-、H2-和H3-T6SS。T6SS通过介导细菌间竞争、生物被膜的形成、金属离子的摄取以及与真核宿主细胞之间的相互作用,对铜绿假单胞菌在毒力和适应环境方面发挥重要作用。本文主要对铜绿假单胞菌T6SS的组装、效应蛋白的分泌、功能及调控机制展开综述,旨在为T6SS的研究提供一定的参考,并为铜绿假单胞菌感染的预防和治疗提供一定的指导。展开更多
Aeromonas hydrophila,an opportunistic pathogen,often encodes Type VI Secretion System(T6SS)genes.However,the specific functions of T6SS,particularly in the context of clinical strains,remain poorly understood.In this ...Aeromonas hydrophila,an opportunistic pathogen,often encodes Type VI Secretion System(T6SS)genes.However,the specific functions of T6SS,particularly in the context of clinical strains,remain poorly understood.In this study,we characterize a multi-drug-resistant strain,AH54,which possesses a complete and functional T6SS,composed of a structural cluster and two homologous auxiliary clusters(Aux1 and Aux2).Each auxiliary cluster encodes two distinct effector proteins:a rearrangement hotspot(Rhs)protein and a proline–alanine–arginine repeat(PAAR)protein—Rhs1/PAAR1 in Aux1 and Rhs2/PAAR2 in Aux2.Our findings reveal that AH54 assembles a fully operational T6SS capable of delivering these effectors,driving inter-bacterial antagonism.Interestingly,the T6SS activity in AH54 is temperature-regulated,with enhanced secretion and antibacterial activity at lower temperatures.To protect itself from self-intoxication,AH54 produces immunity proteins(Tsi1–Tsi4)that neutralize the toxic effectors.While PAAR1 and PAAR2 are critical for Hcp secretion,immunity proteins Tsi3 and Tsi4 do not cross-protect against PAAR effectors,suggesting distinct roles for each PAAR protein in optimizing AH54's competitive fitness.In addition,using a Dictyostelium discoideum phagocytosis model,we demonstrate that Rhs2,a metal ion-dependent DNase effector,plays a crucial role in protecting AH54 from eukaryotic predation via T6SS.These findings highlight the pivotal role of T6SS in bacterial competition and pathogenesis,offering new insights into the virulence mechanisms of A.hydrophila.展开更多
VI型分泌系统(type VI secretion system,T6SS)具有转运效应蛋白分子到多种类型靶细胞的能力,广泛存在于革兰氏阴性菌,其结构复杂。当前T6SS结构模型表明其装置至少包含两个复合物:细胞膜跨膜相关装置和动态的噬菌体样结构。本文主要围...VI型分泌系统(type VI secretion system,T6SS)具有转运效应蛋白分子到多种类型靶细胞的能力,广泛存在于革兰氏阴性菌,其结构复杂。当前T6SS结构模型表明其装置至少包含两个复合物:细胞膜跨膜相关装置和动态的噬菌体样结构。本文主要围绕T6SS分泌装置的结构、结构元件相互作用功能以及影响装置表达和活性的条件和信号来进行简要综述。展开更多
文摘作为一种对抗真核细胞和原核细胞的强有力细菌武器,VI型分泌系统(type VI secretion system,T6SS)广泛存在于革兰氏阴性菌中。铜绿假单胞菌是一种对多种抗生素具有耐药性并能够在人体引发急性和慢性感染的条件致病菌,它编码3套独立的T6SS,分别为H1-、H2-和H3-T6SS。T6SS通过介导细菌间竞争、生物被膜的形成、金属离子的摄取以及与真核宿主细胞之间的相互作用,对铜绿假单胞菌在毒力和适应环境方面发挥重要作用。本文主要对铜绿假单胞菌T6SS的组装、效应蛋白的分泌、功能及调控机制展开综述,旨在为T6SS的研究提供一定的参考,并为铜绿假单胞菌感染的预防和治疗提供一定的指导。
基金supported by the National Natural Science Foundation of China under Grants(32270061 and 32100019)Shenzhen Science and Technology Program under Grant(KQTD20200909113758004).
文摘Aeromonas hydrophila,an opportunistic pathogen,often encodes Type VI Secretion System(T6SS)genes.However,the specific functions of T6SS,particularly in the context of clinical strains,remain poorly understood.In this study,we characterize a multi-drug-resistant strain,AH54,which possesses a complete and functional T6SS,composed of a structural cluster and two homologous auxiliary clusters(Aux1 and Aux2).Each auxiliary cluster encodes two distinct effector proteins:a rearrangement hotspot(Rhs)protein and a proline–alanine–arginine repeat(PAAR)protein—Rhs1/PAAR1 in Aux1 and Rhs2/PAAR2 in Aux2.Our findings reveal that AH54 assembles a fully operational T6SS capable of delivering these effectors,driving inter-bacterial antagonism.Interestingly,the T6SS activity in AH54 is temperature-regulated,with enhanced secretion and antibacterial activity at lower temperatures.To protect itself from self-intoxication,AH54 produces immunity proteins(Tsi1–Tsi4)that neutralize the toxic effectors.While PAAR1 and PAAR2 are critical for Hcp secretion,immunity proteins Tsi3 and Tsi4 do not cross-protect against PAAR effectors,suggesting distinct roles for each PAAR protein in optimizing AH54's competitive fitness.In addition,using a Dictyostelium discoideum phagocytosis model,we demonstrate that Rhs2,a metal ion-dependent DNase effector,plays a crucial role in protecting AH54 from eukaryotic predation via T6SS.These findings highlight the pivotal role of T6SS in bacterial competition and pathogenesis,offering new insights into the virulence mechanisms of A.hydrophila.
文摘VI型分泌系统(type VI secretion system,T6SS)具有转运效应蛋白分子到多种类型靶细胞的能力,广泛存在于革兰氏阴性菌,其结构复杂。当前T6SS结构模型表明其装置至少包含两个复合物:细胞膜跨膜相关装置和动态的噬菌体样结构。本文主要围绕T6SS分泌装置的结构、结构元件相互作用功能以及影响装置表达和活性的条件和信号来进行简要综述。
