耐药的“超级病菌”为何如此顽强?

【耐药的“超级病菌”为何如此顽强?】你可能听说过“抗生素耐药性”带来的一个日益严重的问题,即超级病菌的传播——我们通常用抗生素来杀死病菌,但超级病菌已进化到产生了耐药性。如果不及时解决此问题,那么它可能会对全球健康和疾病造成十分严重的影响。
如今,研究人员在寻找解决方法的道路上迈出了重要一步。一项新研究发现了这些耐药细菌细胞维持防御屏障的方法。如果我们能够通过进一步研究,找到办法攻破城墙(而非直接以细菌为目标),那么我们便可以从源头防止病菌产生耐药性。
该发现的关键在于“钻石光源”,这是一种复杂的科研设备,它能够从原子水平发射出强烈光束,对细菌进行检验。这回,它被用于研究“革兰氏阴性细菌”——其细胞拥有不透水的脂质外膜,因此对抗生素产生了强大的抵抗力。
东英吉利亚大学的科学家专门对这种膜进行了研究。之前,他们曾成功鉴定出细胞屏障的特定弱点。如今,他们发现了这道墙的筑造过程及维护方法,而这是寻找方法攻破城墙的关键步骤。主要研究人员Changjiang Dong解释道:
β桶状蛋白质构成了细胞城墙的大门,它负责向内运输营养物质,并分泌重要生物分子。“β桶状组装机器”负责建筑细胞城墙的这扇大门(即β桶状蛋白质),而阻止“β桶状组装机器”构筑大门则会导致细菌的死亡。
他们对大肠杆菌进行研究,发现在“旋转嵌入”机制形成外膜蛋白质之前,有5个亚单元形成了一个环状结构。如今,这个复杂的“β桶状组装机器”流程已被揭晓,这为下一代药物研发铺平了道路。
由于人体细胞的线粒体结构的形成方式和“β桶状组装机器”相似,因此该发现或许也有助于我们更好地理解自己的身体,尤其是帕金森等疾病(出现于线粒体开始分解之时)。

http://www.sciencealert.com/scientists-figure-out-why-drug-resistant-superbugs-are-so-hard-to-kill

Scientists have figured out why drug-resistant 'superbugs' are so hard to kill

Breaking down cell walls.

You may have already heard about the growing problem caused by antibiotic resistance - the spread of superbugs that have evolved to become resistant to the antibiotics we usually attack them with. It's an issue that could have very serious implications for global health and disease if it isn't tackled urgently, and now researchers have made an important step in finding a solution.

A new study has discovered how these drug-resistant bacterial cells maintain a defensive barrier, and if further research can find a way to bring down these walls - rather than targeting the bacteria directly - the bacteria could be prevented from developing drug resistance in the first place.

Key to the discovery is a sophisticated piece of scientific equipment called theDiamond Light Source, which is capable of emitting intense beams of light to examine bacteria at an atomic level. In this case, it was used to study a particularly stubborn type of bacteria called gram-negative bacteria. Gram-negative bacteria cells have impermeable, lipid-based outer membranes that make them particularly resistant to antibiotics.

It's this membrane that scientists from the University of East Anglia in the UK focussed on, building on previous work where they managed to identify a specific weakness in the cell barrier. Now they've uncovered how the wall is built and maintained - a crucial step forward in working out how to eventually crack it.

"Beta-barrel proteins form the gates of the cell wall for importing nutrition and secreting important biological molecules," lead researcher Changjiang Dong explains. "The beta-barrel assembly machinery (BAM) is responsible for building the gates (beta-barrel proteins) in the cell wall. Stopping the beta-barrel assembly machine from building the gates in the cell wall cause the bacteria to die."

In the E.coli bacteria studied by Dong and his team, five subunits form a ring structure before using a 'rotation and insertion' mechanism to build up outer membrane proteins. Now that this complex BAM process has been revealed, it opens the way for next-generation drugs to be developed.

Because the mitochondria structures inside human cells are constructed in a similar way to the beta-barrel assembly machinery, the discovery could help us understand more about own own bodies as well, particularly with regards to diseases like Parkinson's (which appear when the mitochondria begin to break down).

"Our work is the first to show the entire BAM complex," says Dong, adding that targeting the BamA subunit could be a way of providing effective treatments to fight superbugs in the future.

The team's work has been published in Nature.

 


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