The genome of a pathogenic rhodococcus: cooptive virulence underpinned by key gene acquisitions.
The genome of a pathogenic rhodococcus: cooptive virulence underpinned by key gene acquisitions.
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DOI：
10.1371/journal.pgen.1001145
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发表时间：
2010-09-30
期刊：
影响因子：
4.5
通讯作者：
Vázquez-Boland JA
中科院分区：
文献类型：
--
作者：
Letek M;González P;Macarthur I;Rodríguez H;Freeman TC;Valero-Rello A;Blanco M;Buckley T;Cherevach I;Fahey R;Hapeshi A;Holdstock J;Leadon D;Navas J;Ocampo A;Quail MA;Sanders M;Scortti MM;Prescott JF;Fogarty U;Meijer WG;Parkhill J;Bentley SD;Vázquez-Boland JA
我们报道了兼性细胞内寄生虫马红球菌的基因组，它是生物技术上重要的放线杆菌属红球菌中唯一的动物病原体。马立克氏杆菌103S基因组长度为5.0Mb，明显小于环境毒株的基因组。这是由于非致病物种的基因组扩张，通过平行基因的线性获得和加速的遗传流量，而不是马立克氏杆菌的减缩进化。103S基因组缺乏环境中红球菌广泛的分解代谢和次生代谢补充，它对宿主在富含脂肪酸的短链肠道和草食动物粪便中的定植和竞争表现出独特的适应能力-这是马立克的两个主要储存库。除了少数水平获得性(HGT)致病基因，包括巨噬细胞生存所需的细胞黏附毛决定簇(RPL)和毒力质粒vap致病性岛(PAI)外，大多数在环境中发现的潜在毒力相关基因在环境中是保守的，或者在非致病放线菌中有同源基因。这表明了一种毒力进化的机制，该机制基于关键宿主生态位适应性HGT事件触发的现有核心放线菌性状的共选。我们通过研究马立克氏杆菌毒力质粒-染色体串扰，通过全球转录图谱和表达网络分析来验证这一假说。在环境红球菌中保守的两个染色体基因编码参与芳香氨基酸生物合成的分支酸变位酶和邻氨基苯甲酸合成酶，它们与vap PAI毒力基因强烈协同调节，是巨噬细胞最佳增殖所必需的。因此，染色体代谢基因在HGT获得质粒PAI控制下的调控整合是马立克氏杆菌协同毒力的重要因素。红球菌是放线菌中的一个原型属，放线菌是地球上最大的微生物群之一。由于其代谢的多功能性和生物降解性，许多无处不在的红球菌物种在生物技术上是有用的。我们已经破译了兼性寄生红球菌的基因组，这是一种动物和人类的病原体马立克红球菌。近缘物种的比较基因组分析提供了一个独特的机会来增加我们对生态位适应性基因组进化和专业化的理解。环境中的红球菌基因组更大，代谢和降解途径更丰富，这是由于基因复制和获得，而不是马立克氏杆菌的基因组收缩。这可能反映了与寄主相关的马红假单胞菌的栖息地比非致病红球菌的化学多样性但营养不良的环境生态位更稳定和有利，这需要代谢上更复杂的、扩大的基因组。我们的工作还强调，在水平获取提供宿主生态位的几个关键基因之后，核心微生物特征的招募或共选是放线杆菌毒力进化的重要机制。基因共选是一种关键的进化机制，允许快速适应变化和获得新的性状。认识到共选择对毒力的贡献，为理解和解释微生物致病力的出现和进化提供了一个合理的框架。
We report the genome of the facultative intracellular parasite Rhodococcus equi, the only animal pathogen within the biotechnologically important actinobacterial genus Rhodococcus. The 5.0-Mb R. equi 103S genome is significantly smaller than those of environmental rhodococci. This is due to genome expansion in nonpathogenic species, via a linear gain of paralogous genes and an accelerated genetic flux, rather than reductive evolution in R. equi. The 103S genome lacks the extensive catabolic and secondary metabolic complement of environmental rhodococci, and it displays unique adaptations for host colonization and competition in the short-chain fatty acid–rich intestine and manure of herbivores—two main R. equi reservoirs. Except for a few horizontally acquired (HGT) pathogenicity loci, including a cytoadhesive pilus determinant (rpl) and the virulence plasmid vap pathogenicity island (PAI) required for intramacrophage survival, most of the potential virulence-associated genes identified in R. equi are conserved in environmental rhodococci or have homologs in nonpathogenic Actinobacteria. This suggests a mechanism of virulence evolution based on the cooption of existing core actinobacterial traits, triggered by key host niche–adaptive HGT events. We tested this hypothesis by investigating R. equi virulence plasmid-chromosome crosstalk, by global transcription profiling and expression network analysis. Two chromosomal genes conserved in environmental rhodococci, encoding putative chorismate mutase and anthranilate synthase enzymes involved in aromatic amino acid biosynthesis, were strongly coregulated with vap PAI virulence genes and required for optimal proliferation in macrophages. The regulatory integration of chromosomal metabolic genes under the control of the HGT–acquired plasmid PAI is thus an important element in the cooptive virulence of R. equi. Rhodococcus is a prototypic genus within the Actinobacteria, one of the largest microbial groups on Earth. Many of the ubiquitous rhodococcal species are biotechnologically useful due to their metabolic versatility and biodegradative properties. We have deciphered the genome of a facultatively parasitic Rhodococcus, the animal and human pathogen R. equi. Comparative genomic analyses of related species provide a unique opportunity to increase our understanding of niche-adaptive genome evolution and specialization. The environmental rhodococci have much larger genomes, richer in metabolic and degradative pathways, due to gene duplication and acquisition, not genome contraction in R. equi. This probably reflects that the host-associated R. equi habitat is more stable and favorable than the chemically diverse but nutrient-poor environmental niches of nonpathogenic rhodococci, necessitating metabolically more complex, expanded genomes. Our work also highlights that the recruitment or cooption of core microbial traits, following the horizontal acquistion of a few critical genes that provide access to the host niche, is an important mechanism in actinobacterial virulence evolution. Gene cooption is a key evolutionary mechanism allowing rapid adaptive change and novel trait acquisition. Recognizing the contribution of cooption to virulence provides a rational framework for understanding and interpreting the emergence and evolution of microbial pathogenicity.
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影响因子：
3.2
作者：
Eschbach, M;Schreiber, K;Schobert, M
通讯作者：
Schobert, M
DOI：
10.1073/pnas.012363899
发表时间：
2002-01-08
影响因子：
11.1
作者：
Chico-Calero, I;Suárez, M;Vázquez-Boland, JA
通讯作者：
Vázquez-Boland, JA
结核分枝杆菌通用应激蛋白 Rv2623 通过 ATP 结合调节细菌生长：建立慢性持续感染的必要条件。
影响因子：
6.7
作者：
Drumm JE;Mi K;Bilder P;Sun M;Lim J;Bielefeldt-Ohmann H;Basaraba R;So M;Zhu G;Tufariello JM;Izzo AA;Orme IM;Almo SC;Leyh TS;Chan J
通讯作者：
Chan J
影响因子：
14.9
作者：
Finn RD;Mistry J;Tate J;Coggill P;Heger A;Pollington JE;Gavin OL;Gunasekaran P;Ceric G;Forslund K;Holm L;Sonnhammer EL;Eddy SR;Bateman A
通讯作者：
Bateman A
影响因子：
64.8
作者：
Bentley, SD;Chater, KF;Hopwood, DA
通讯作者：
Hopwood, DA