Novel type III effectors in Pseudomonas aeruginosa.
Novel type III effectors in Pseudomonas aeruginosa.
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DOI：
10.1128/mbio.00161-15
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发表时间：
2015-03-17
期刊：
影响因子：
6.4
通讯作者：
Banin E
中科院分区：
文献类型：
--
作者：
Burstein D;Satanower S;Simovitch M;Belnik Y;Zehavi M;Yerushalmi G;Ben-Aroya S;Pupko T;Banin E
铜绿假单胞菌是一种革兰氏阴性的机会性病原体，可引起免疫功能低下患者的慢性和急性感染。大多数铜绿假单胞菌菌株编码一个活跃的III型分泌系统（T3SS），细菌利用该系统将效应蛋白从细菌细胞直接输送到宿主细胞的细胞质中。在铜绿假单胞菌中发现并广泛研究了四种T3SS效应物：ExoT， ExoS， ExoU和ExoY。考虑到铜绿假单胞菌感染多种宿主的能力，这一点尤其有趣。因此，我们假设在铜绿假单胞菌的基因组中编码了其他尚未发现的T3SS效应物。在这里，我们应用机器学习分类算法来识别新的铜绿假单胞菌效应物。在这种方法中，整合了各种类型的数据，以区分细菌基因组的其他开放阅读框中的效应子。由于缺乏足够的正效应物学习集，我们的机器学习算法整合了另一种假单胞菌物种的基因组信息，并利用了数十个特征，说明了效应物编码基因及其产物的各个方面。对T3SS特异性易位的12个预测进行了实验测试，发现了两个新的T3SS效应物。我们证明这些效应器不是注入结构复合物的一部分，并报告了对其表征的初步努力。铜绿假单胞菌使用III型分泌系统（T3SS）将称为效应物的有毒蛋白直接分泌到宿主细胞的细胞质中。该分泌系统的激活与疾病严重程度和患者死亡相关。与许多其他利用t3ss的致病菌相比，铜绿假单胞菌具有相当有限的已确定的效应物库。这与这种细菌可以感染的广泛宿主形成鲜明对比。本文描述的两种新型效应物的发现是更好地了解这种多功能病原体所采用的毒力和宿主逃避机制的重要一步，并可能为治疗铜绿假单胞菌感染提供新的方法。
Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that causes chronic and acute infections in immunocompromised patients. Most P. aeruginosa strains encode an active type III secretion system (T3SS), utilized by the bacteria to deliver effector proteins from the bacterial cell directly into the cytoplasm of the host cell. Four T3SS effectors have been discovered and extensively studied in P. aeruginosa: ExoT, ExoS, ExoU, and ExoY. This is especially intriguing in light of P. aeruginosa’s ability to infect a wide range of hosts. We therefore hypothesized that additional T3SS effectors that have not yet been discovered are encoded in the genome of P. aeruginosa. Here, we applied a machine learning classification algorithm to identify novel P. aeruginosa effectors. In this approach, various types of data are integrated to differentiate effectors from the rest of the open reading frames of the bacterial genome. Due to the lack of a sufficient learning set of positive effectors, our machine learning algorithm integrated genomic information from another Pseudomonas species and utilized dozens of features accounting for various aspects of the effector coding genes and their products. Twelve top-ranking predictions were experimentally tested for T3SS-specific translocation, leading to the discovery of two novel T3SS effectors. We demonstrate that these effectors are not part of the injection structural complex and report initial efforts toward their characterization. Pseudomonas aeruginosa uses a type III secretion system (T3SS) to secrete toxic proteins, termed effectors, directly into the cytoplasm of the host cell. The activation of this secretion system is correlated with disease severity and patient death. Compared with many other T3SS-utilizing pathogenic bacteria, P. aeruginosa has a fairly limited arsenal of effectors that have been identified. This is in sharp contrast with the wide range of hosts that this bacterium can infect. The discovery of two novel effectors described here is an important step toward better understanding of the virulence and host evasion mechanisms adopted by this versatile pathogen and may provide novel approaches to treat P. aeruginosa infections.