Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.
Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.
复制标题
盗版保守的噬菌体机制促进了混杂的葡萄球菌致病岛转移。
DOI：
10.7554/elife.26487
复制
发表时间：
2017-08-08
期刊：
影响因子：
7.7
通讯作者：
Penadés JR
中科院分区：
文献类型：
--
作者：
Bowring J;Neamah MM;Donderis J;Mir-Sanchis I;Alite C;Ciges-Tomas JR;Maiques E;Medmedov I;Marina A;Penadés JR
针对保守的和必要的过程是一个成功的战略，以打击敌人。值得注意的是，临床上重要的金黄色葡萄球菌致病岛（SaPI）使用这种策略在自然界中传播。SaPI被动地驻留在宿主染色体中，在SaPI编码的主阻遏物Stl的控制下。已经假设SaPI去阻遏受结合Stl的特异性噬菌体蛋白影响，从而启动SaPI循环。不同的SaPI编码不同的Stl阻遏物，因此每种都靶向特定的噬菌体蛋白以进行去阻遏。扩大这种狭隘的视野，我们在这里报告说，SaPI确保其混杂的转移，针对保守的噬菌体机制。这是因为SaPI Stl阻遏物已经获得了不同的结构域以与由不同cDNA编码的不相关的蛋白质相互作用，但在所有情况下执行相同的保守功能。这种优雅的策略允许属内和属间SaPI转移，突出了这些元素作为自然界最迷人的亚细胞寄生虫之一。许多有害微生物可以产生不同的分子，使它们更有效地引起和传播疾病。这些分子也可以从“移动的遗传元件”中获得，这些遗传元件可以在种群内的细菌之间转移。致病岛就是这样一种移动的遗传因子，在葡萄球菌中非常常见。它们在细菌之间传播毒素编码基因，包括一种可能导致人类中毒性休克综合征的基因。致病岛通常存在于细菌的DNA中，在那里它们被特定的阻遏蛋白灭活。然而，在另一种移动的遗传元件-噬菌体-存在的情况下，阻遏蛋白开始与噬菌体编码的特定蛋白相互作用。这使得致病岛变得活跃并传播给其他细菌。先前的研究表明，在被称为金黄色葡萄球菌的细菌中，不同的致病岛具有不同的阻遏物。因此，科学家们假设阻遏物只能与某些噬菌体蛋白相互作用。然而，由于致病岛在自然界中广泛存在，它们可能使用其他方式劫持噬菌体机器以确保其转移。为了验证这一假设，Bowring等研究了沙门氏菌中两种类型的致病岛。金黄色葡萄球菌，并揭示了他们的两个不同的阻遏物不与特定的噬菌体蛋白质相互作用，如以前假设的。相反，每个阻遏物可以与多种具有各种不同结构的噬菌体蛋白相互作用，包括来自完全不同噬菌体的蛋白质。Bowring等人还发现，每一种分析的阻遏蛋白实际上并不识别噬菌体蛋白上任何特定的共有结构特征，而是进化为在各种噬菌体中发挥相同作用的靶蛋白。这表明阻遏物靶向特定的过程，而不是单一的蛋白质。这种策略允许它们在同一物种内转移，但也可以在不同物种之间转移。下一步将是更好地了解阻遏物如何识别结构上不相关的蛋白质，并确定是什么进化力量推动了这一现象。更深入地了解致病岛如何在葡萄球菌之间传播对于了解这些细菌如何对抗生素等治疗产生耐药性至关重要。
Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaPI de-repression is effected by specific phage proteins that bind to Stl, initiating the SaPI cycle. Different SaPIs encode different Stl repressors, so each targets a specific phage protein for its de-repression. Broadening this narrow vision, we report here that SaPIs ensure their promiscuous transfer by targeting conserved phage mechanisms. This is accomplished because the SaPI Stl repressors have acquired different domains to interact with unrelated proteins, encoded by different phages, but in all cases performing the same conserved function. This elegant strategy allows intra- and inter-generic SaPI transfer, highlighting these elements as one of nature’s most fascinating subcellular parasites. Many harmful microbes can produce different molecules that make them more effective in causing and spreading diseases. These molecules can also be obtained from ‘mobile genetic elements’ that can be transferred between bacteria within a population. Pathogenicity islands are one such type of mobile genetic element and are very common among bacteria known as staphylococci. They spread toxin-encoding genes between bacteria, including one that can lead to a condition called toxic shock syndrome in humans. Pathogenicity islands are normally found within the DNA of the bacteria, where they are deactivated by specific repressor proteins. However, in the presence of another type of mobile genetic element – the bacteriophages – the repressor proteins start to interact with specific proteins encoded by the bacteriophages. This allows the pathogenicity islands to become active and spread to other bacteria. Previous research has shown that in the bacterium known as Staphylococcus aureus, different pathogenicity islands have different repressors. Scientists therefore assumed that the repressors are only able to interact with certain bacteriophage proteins. However, since pathogenicity islands are widespread in nature, it could be possible that they use other ways to hijack the bacteriophage machinery to ensure their transfer. To test this hypothesis, Bowring et al. studied two types of pathogenicity islands in S. aureus and revealed that their two different repressors did not interact with specific bacteriophage proteins as previously hypothesized. Instead, each repressor could interact with multiple bacteriophage proteins that had a variety of different structures, including proteins from completely different bacteriophages. Bowring et al. also discovered that each of the analyzed repressor proteins did not actually recognize any specific shared structural features on the bacteriophage proteins, but rather evolved to target proteins that play the same role in various bacteriophages. This suggests the repressors target a specific process rather than a single protein. This strategy allows them to be transferred within the same species, but also between different ones. A next step will be to better understand how a repressor can recognize structurally unrelated proteins, and establish what evolutionary forces are driving this phenomenon. A deeper knowledge of how pathogenicity islands spread between staphylococci is vital to understand how these bacteria can become resistant to treatments such as antibiotics.