Smuggling a CRISPR gene editor into staph bacteria can kill the pathogen

诚信胡子 2018-10-13

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Smuggling a CRISPR gene editor into staph bacteria can kill the pathogen携带CRISPR基因编辑器进入葡萄球菌可以杀死病原体

The technique takes advantage of the way the microbes naturally swap genes to become more harmful这项技术利用了微生物自然交换基因的方式，使其变得更加有害

BY LAUREL HAMERS 9:00AM, OCTOBER 1, 2018

BATTLING A SUPERBUG A new approach to fighting antibiotic-resistance Staphylococcus aureus bacteria (purple spheres, shown in this scanning electron microscope image being ingested by a white blood cell) co-opts genes that normally make the bacteria more dangerous.一种对抗耐抗生素金黄色葡萄球菌的新方法(在这张扫描电子显微镜图像中显示的紫色球体被白细胞吞噬)选择了通常使这种细菌更加危险的基因。

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Bits of DNA that make bacteria dangerous can be co-opted to bring the microbes down instead.让细菌变得危险的DNA片段可以被用来杀死细菌。

Stretches of DNA called pathogenicity islands can jump between bacteria strains, introducing new toxin-producing genes that usually make a strain more harmful. 一段被称为致病性岛的DNA可以在菌株之间跳跃，引入新的产生毒素的基因，这通常会使菌株更加有害Scientists have now modified pathogenicity islands by replacing the toxin-producing genes with genes that, in mice, disabled or killed Staphylococcus aureus bacteria. If the approach works for humans, it could offer an alternative to traditional antibiotics that could one day be used against deadly drug-resistant金黄色葡萄球菌的细菌。如果这种方法适用于人类，它可能会提供一种替代传统抗生素的方法，有朝一日这种抗生素可能被用于治疗致命的耐药性 Staphylococcus strains, researchers report September 24 in Nature Biotechnology.

Pathogenicity islands are already primed for such inside jobs: The stretches of DNA naturally get bundled into small parcels that can easily enter bacteria to deliver new genes. Researchers turned those parcels into Trojan horses of sorts, replacing the toxin-producing genes with sequences of the gene-editing tool CRISPR/Cas9, which snips DNA in specific places.研究人员把这些包裹变成了特洛伊木马，用基因编辑工具CRISPR/Cas9的序列取代了产生毒素的基因，CRISPR/Cas9可以在特定的地方剪切DNA。

In one version, the Cas9 cuts the staph DNA, killing the bacteria. In another, a modified version of CRISPR/Cas9 doesn’t make any cuts; instead, the Cas9 latches onto a gene that controls how dangerous staph bacteria are to make them less effective at causing infection.在另一个版本中，CRISPR/Cas9的修改版本没有进行任何剪切;相反，Cas9锁定在一个控制葡萄球菌的危险程度的基因上，从而降低了它们引起感染的效率

Researchers tested these DNA-loaded parcels, which they refer to as “drones,” in mice. Both versions, when injected under mice’s skin, stopped the animals from developing an abscess. And the mice that received the bacteria-killing version survived a lethal injection of S. aureus in their body cavity.接受了这种杀菌方式的老鼠在体内注射了金黄色葡萄球菌后存活了下来。

The drone treatment is somewhat akin to phage therapy, an alternative to antibiotics where patients are given a cocktail of different bacteriophages, viruses that target bacteria 这种无人机疗法有点类似于噬菌体疗法。噬菌体疗法是一种替代抗生素的疗法，在这种疗法中，患者会被注射不同的噬菌体，即针对细菌的病毒(SN Online: 5/20/13). Phage therapy, often used against multidrug resistant infections, isn’t currently approved for use in the United States, but is common in Eastern Europe.

But the drone approach is simpler, says coauthor Richard Novick, a microbiologist at the New York University School of Medicine. For a phage to kill a cell, it needs to reproduce inside the cell. But with a drone, “all it has to do is express one gene, and that'll kill the bacteria.”但是，纽约大学医学院的微生物学家理查德·诺维克(Richard Novick)说，无人机的方法更简单。噬菌体要杀死一个细胞，它需要在细胞内繁殖。但对于无人机来说，“它只需要表达一个基因，就能杀死细菌。”

That’s a very effective way to target Staphylococcus bacteria, says Gail Christie, a microbiologist at the Virginia Commonwealth University School of Medicine in Richmond who wasn’t part of the study.

Resistance might still be an issue with the new approach, though. A few bacteria strains didn’t react to either version of the treatment in mice.不过，这种新方法可能仍然存在阻力。一些菌株对两种治疗方法都没有反应 If the approach is used clinically — and that’s still a long way away — a patient would probably receive multiple kinds of drones that target the bacteria in different ways, Novick says.诺维克说，如果这种方法在临床上得到应用——而且还需要很长的一段路要走——病人可能会接受多种无人机，以不同的方式瞄准细菌。

A next step is to test the system in other infections that can be caused by staph bacteria, such as pneumonia, he says.

Citations

G. Ram et al. Conversion of staphylococcal pathogenicity islands to CRISPR-carrying antibacterial agents that cure infections in mice. Nature Biotechnology. Published online September 24, 2018. doi:10.1038/nbt.4203.