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BMC Genomics:以毒攻毒——“吸血鬼”细菌能用作活体抗生素

来源:sciencedaily 2011-11-02 09:41

(图:黄色即狩猎者Micavibrio aeruginosavorus,紫色即猎物Pseudomonas aeruginosa,周围灰色则是已经死亡的Pseudomonas aeruginosa;右上角是Micavibrio aeruginosavorus的基因组图)

近日,一项研究表明,一种类似“吸血鬼”的细菌(可转移到其它特定细菌上,包括某些人类病原体)可用作许多感染性疾病的活体抗生素。

该细菌命名为Micavibrio aeruginosavorus,大约30年前在废水中被发现。由于常规的微生物学技术难以对其进行培养和研究,因此一直没用对其开展广泛的研究。尽管如此,美国维吉尼亚大学艺术与科学学院的生物学家Martin Wu和Zhang Wang解码了该细菌的基因组,以研究“它们是如何生存的”。

这种细菌的生存方式是通过找到其它种类的细菌作为其猎物,粘附到它们的细胞壁上并吸取养分。和其它大部分从周围环境汲取养分的细菌不同,M. aeruginosavorus只能通过汲取其它细菌的养分来生存和繁殖。这会杀死它的宿主细菌,因此可作为摧毁有害病原体的潜在有效工具。

该细菌的其中一种宿主细菌是Pseudomonas aeruginosavorus,它是引起囊性纤维化病人严重肺部感染的主要病因。

Wu说道:“因为这种细菌能找出并攻击特定对人类有害的细菌,病理学家可以利用这些细菌来“以火灭火”。”

该研究的论文发表在最新一期的《BMC Genomics》杂志上。

Wu说道:“我们实验室使用了最尖端技术来解码该种细菌的基因组。我们对其寻找和攻击宿主的分子机制相当感兴趣。在几年前,关于这方面的研究非常的困难且需要大量的资金。”

传统抗生素的滥用使得“超级细菌”的出现。目前急需新技术实现既能杀死病原体,又不会使它们产生任何抗性。

由于M. aeruginosavorus细菌对宿主非常具有选择性,它对人体内数千种有益细菌并无毒害作用。因此,使用它来做为活体抗生素,不但能降低我们对传统抗生素的依赖性,还可以减缓细菌抗药性的问题。

该细菌的另一个优势就是它们能在黏性流体中游动,比如P. aeruginosavorus病菌会在囊性纤维化病人的肺部形成一种跟胶水一样的生物膜,来增强其对传统抗生素的抵抗性。我们注意到M. aeruginosavorus可以在这种黏液中游动,并攻击P. aeruginosavorus病菌。

Wu认为,对于M. aeruginosavorus还需要更进一步的研究以了解它们的基因功能,才能使其更好的利用在人类疾病治疗中。(生物谷 Bioon.com)

Genomic insights into an obligate epibiotic bacterial predator: Micavibrio aeruginosavorus ARL-13

Zhang Wang , Daniel E Kadouri and Martin Wu

Background

Although bacterial predators play important roles in the dynamics of natural microbial communities, little is known about the molecular mechanism of bacterial predation and the evolution of diverse predatory lifestyles.

Results

We determined the complete genome sequence of Micavibrio aeruginosavorus ARL-13, an obligate bacterial predator that feeds by "leeching" externally to its prey. Despite being an obligate predator depending on prey for replication, M. aeruginosavorus encodes almost all major metabolic pathways. However, our genome analysis suggests that there are multiple amino acids that it can neither make nor import directly from the environment, thus providing a simple explanation for its strict dependence on prey. Remarkably, despite apparent genome reduction, there is a massive expansion of genomic islands of foreign origin. At least nine genomic islands encode many genes that are likely important for Micavibrio-prey interaction such as hemolysin-related proteins. RNA-Seq analysis shows substantial transcriptome differences between the attack phase, when M. aeruginosavorus seeks its prey, and the attachment phase, when it feeds and multiplies. Housekeeping genes as well as genes involved in protein secretion were all dramatically up-regulated in the attachment phase. In contrast, genes involved in chemotaxis and flagellum biosynthesis were highly expressed in the attack phase but were shut down in the attachment phase. Our transcriptomic analysis identified additional genes likely important in Micavibrio predation, including porins, pilins and many hypothetical genes.

Conclusions

The findings from our phylogenomic and transcriptomic analyses shed new light on the biology and evolution of the epibiotic predatory lifestyle of M. aeruginosavorus. The analysis reported here and the availability of the complete genome sequence should catalyze future studies of this organism.

Keywords:

Bacterial predation; Predator-prey interaction; Integrative and conjugative elements (ICEs); Hemolysin-related protein; Quorum sensing, RNA-Seq

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