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六个阻止抗生素耐药性的好想法

更新时间:2017-11-6 13:36:57 来源:纽约时报中文网 作者:佚名

Six grand ideas to fight the end of antibiotics
六个阻止抗生素耐药性的好想法

The world is nearing a moment when antibiotics no longer work to treat infections. We are severely over-using the antibiotics we have – and that system is causing bacteria to evolve and develop resistance to the drugs intended to kill them.

世界正进入抗生素对感染不起作用的时代。我们现在正在严重滥用抗生素——这一情况导致细菌不断进化,发展出对药物的耐药性。

Appropriately, the phenomenon is referred to as antibiotic resistance, and it’s shaped up to be one of the biggest challenges we face in the 21st Century.

这种现象一般被称为耐药性,它已经成为21世纪人类面临的最大挑战之一。

The stakes are high. The good news? A whole slew of governments, organisations, innovators, and scientists across the globe is pondering how to get us out of this mess. Here are just a few of the many methods being employed in the fight against antibiotic resistance.

该问题举足轻重。好消息是全世界的很多政府、组织、创新者和科学家都在研究如何走出这一困境。以下是应对抗生素耐药性的一些方法。

USING BACTERIA AGAINST ITSELF

用细菌来对抗细菌

If drugs fail, why not fight fire with fire?

如果药物不起作用,为什么不以毒攻毒?

Several new biotech companies are hoping to use our growing understanding of the human microbiome: healthy microbes that live in the human body, which boost our immune system, prevent infection, and regulate metabolism. It could help develop a new class of drugs that fight superbugs – infections resistant to drugs, expected to kill more people than cancer by 2050.

一些新的生物科技公司正希望利用对人类微生物群系日益加深的认识:利用这些生活在人体内能增强免疫系统对人健康有益微生物,来阻止感染,调节新陈代谢。这些公司有望研制出针对超级细菌(有耐药性的感染)的新型药物。预期在2050年之前,死于超级细菌感染的人会超过因癌症死亡的人数。

Vedanta Biosciences, based in Cambridge, Massachusetts, is one firm basing its drug development on the new thought that many bacteria may cause infection because the patient has depleted their own microbiome through overuse of antibiotics. Vedanta is using research conducted on the microbiome around the world to identify good bacteria that they can put in pill form – a swallowable solution that will then enter the gut and stimulate immune response.

位于马萨诸塞州剑桥(Cambridge, Massachusetts)的Vedanta生物科技公司正在基于一个新的观点开发药品。他们认为很多细菌造成感染是因为患者滥用抗生素导致他们体内的微生物群系匮乏。Vedanta公司在全球展开对微生物群系的研究,希望找到合适的细菌并制作成药品——一种可以吞咽的口服液,进入消化道从而激发人体免疫反应。

“Microbiome-based therapies such as bacterial consortia are a much-needed alternative to antibiotics. It is important to look for new ways to treat infection that are both less prone to eliciting resistance and do not damage the microbiota and thus render the host vulnerable to reinfection,” says Bernat Olle, Vedanta CEO.

"微生物群系疗法是一种亟需的抗生素替代疗法。重要的一点是寻找新方法,一方面不容易引起耐药性,另一方面又不会破坏人体的微生物群系,增加再感染的可能性,"Vedanta的首席执行官贝尔纳特·奥列(Bernat Olle)说。

It is important to note, however, that scientists still do not fully understand the human microbiome. But research into how it works is moving at a quick pace and Vedanta is nearing the clinical trial stage for at least two of its drugs. If they work, it could be a game-changer for fighting infections.

不过,值得一提的是,科学家还尚未充分了解人体的微生物群系。但是对微生物群系运作方式的研究正在以较快的速度发展。Vedanta公司至少有两种药物已经接近临床试验阶段。如果它们能够奏效,这就能改变对抗细菌感染的局面。

DEPLOYING TINY SEMICONDUCTORS

部署微型半导体

This idea comes from researchers at the University of Colorado, Boulder, who were working on developing quantum dots for use in harnessing solar energy to make fuel. What are quantum dots? Small crystals of semiconductors – the material we use to make phones and computers. (Small is an understatement. As Prashant Nagpal, a UC researcher on the project says: “A quantum dot is to the width of a hair roughly what a city block is to the Earth.”)

位于博尔德(Boulder)的科罗拉多大学的研究人员正在开发量子点(quantum dots),用来捕获太阳能以制造燃料。量子点是什么?它是微小的半导体晶体——手机和计算机的生产会用到这种材料。("微小"并不足以形容它的尺寸。按照参与该项目的加州大学的研究员普拉桑特·纳格帕尔(Prashant Nagpal)说法:"一个量子点之于一根头发的直径,相当于一个街区之于地球的直径")

Together with colleague Anushree Chattetrjee, who works on developing new therapies for antibiotic treatment, Nagpal wondered if the light-responsive dots could be used to fight superbugs. The result was a new form of quantum dots that can selectively target bacteria.

阿奴希瑞·查特吉(Anushree Chattetrjee)是纳格帕尔的同事,他正在研究关于抗生素治疗的新疗法。纳格帕尔探究了感光性量子点是否有可能用于对抗超级细菌。研究的成果是一种能够选择性针对细菌的新型量子点。

“What it could mean is that these quantum dots can be present everywhere, and when developed completely as a therapy, they can be activated by light to clear infections in animals or humans without killing the host mammalian cells,” Nagpal says. When activated, the dots produce just enough a substance that is toxic to bacterial cells, but harmless to the host’s own cells.

"这可能意味着无处不在的量子点一旦成为成熟的疗法,就能够用光线激活,在不杀死哺乳类动物细胞的情况下消除人或动物的感染,"纳格帕尔说。量子点在激活以后能够产生合适数量的物质,毒死细菌,但对宿主的细胞没有伤害。

When testing the dots in cell cultures, the dots had no effect on healthy human cells. And light exposure to activate them could be as little as a room light or the sun (or a more directed LED for deeper infections).

在细胞培养环境下对量子点的测试发现它们对健康的人体细胞没有影响。要激活这种量子点只需要室内光照或阳光就足够(较严重的感染需要LED灯的直射)

They could theoretically be so effective, that they would only require a one million-times smaller dose than traditional drugs.

理论上说,这种量子点的疗效非常强大,它的剂量是传统药物的一百万分之一。

Quantum dots are easily and cheaply manufactured so scaling them up to treat infections on a worldwide scale would cost just a few cents (or less) per dose.

量子点的制造方法简单,成本低廉,如果把使用范围扩大到全球,一份量子点的成本可能不到几美分。

“A minuscule amount of drug with some light can treat some of the worst superbug infections we tested in clinical strains acquired from a Colorado hospital,” Nagpal says. “Of course, more work and extensive studies in preclinical and clinical trials need to be done before we can administer these quantum dots to patients. However, this initial study shows a lot of promising features.”

"我们在科罗拉多的一家医院获取临床细菌进行测试,通过一些光照加上微量药品就可以治疗一些非常严重的超级细菌感染,"纳格帕尔说,"当然,我们还需要进行大量的临床前试验和临床试验,才能对患者使用量子点疗法。不过,初步研究表明它的前景非常好。"

INFECTION-KILLING POLYMERS

能消除感染的聚合物

Antibiotics may not be the only answer to fighting superbugs. Researchers at the University of Melbourne have discovered a totally unconventional method of killing deadly bacteria.

抗生素可能不是对抗超级细菌的唯一答案。墨尔本大学的研究人员发现了一种极为不同寻常的杀菌方法。

Turns out a star-shaped polymer (a chain of molecules) that they engineered 15 years ago to add viscosity to automotive paints and engine oils has some interesting abilities when it’s re-purposed for biological uses. While researching the polymer’s ability to deliver drugs to treat cancer, the scientists realised that a version of the star called Snapp (Structurally Nanoengineered Antimicrobial Peptide Polymers) had become toxic to bacteria.

15年前,他们开发了一种星形聚合物(链式分子),用来增加汽车喷漆和发动机油的粘度。现在,他们发现一旦将其调整,用于生物学用途,这种聚合物就会产生一些让人感兴趣的能力。当科学家研究这种聚合物传递抗癌药物的时候,他们意识到某个名为Snapp(纳米结构抗微生物肽聚合物)的聚合物对细菌有毒性。

Among other ways of killing the bugs, it has the ability to rip apart their cell walls by becoming absorbed into the cell’s membrane and pulling out its lipid layer.

它有多种杀死细菌的方法,其中之一是侵入细胞壁,扯出脂质层,从而撕裂细菌的细胞壁。

If funding comes through, the researchers think they could be testing this method in humans within five years. “Our star synthesis is an engineering process and can be easily scaled up. It is also not very expensive. The regulatory approval will likely be the slowest step,” says chemical engineer Greg Qiao, whose lab at the Melbourne School of Engineering is responsible for the work.

研究者认为,如果资金到位,他们就可能在五年内开始人体试验。"我们的星形聚合物是一个工程流程,很容易规模化。它的成本并不高。最慢的一步可能会是监管部门的审批,"化学工程师格雷格.乔(Greg Qiao)说。他所在的墨尔本大学工程学院(Melbourne School of Engineering)的实验室正在负责这项工作。

GETTING OUT OF SILOES

走出实验室,合作共赢

One of the biggest problems in medicine, and science in general, is that researchers don’t always work directly with doctors to solve health problems. That means they tend to miss out on key data that can only be gleaned by working directly with patients.

在医学界乃至整个科学界,一个很大的问题是研究人员并不会与医生直接合作解决医疗问题。这就意味着他们会错过只有通过与患者直接合作才能获取的关键数据。

At the Antibiotic Resistance Center at Emory University in Georgia, clinicians and research scientists are working together to better understand how to diagnose and treat resistance. “I’m not a doctor. I need to know from the clinicians a lot of what they’re seeing on the front lines to help guide our research to be as relevant as possible,” says David Weiss, director of the center.

在位于乔治亚州的埃默里大学(Emory University)的抗生素抗药性研究中心(Antibiotic Resistance Center),临床人员和科研人员正在合作,加深对抗药性诊断和治疗的认识。"我不是医生。我需要向临床人员了解他们在前线的所见所闻,指导我们的研究尽可能符合实际情况,"该中心的主管大卫·魏斯(David Weiss)说。

One of the biggest results of this partnership so far has been the development of a new diagnostic test to help doctors discover what bacterium is responsible for resistance inside a patient that’s not responding to antibiotics. Based on the success of this model, Weiss says, other clinical institutions are starting to open their own versions of the centre that brings researchers and doctors together.

到目前为止,这项合作最大的结果之一就是开发出一套新的诊断测试,帮助医生发现是哪种细菌造成了耐药性,导致抗生素对患者不起作用。基于这一成功模式,其他临床机构也开始建立同类的研究中心,让研究人员和医生一起合作,魏斯说。

BRIDGING ACADEMIA AND INDUSTRY

在学术界和行业之间架设桥梁

The world desperately needs new antibiotics, but drug companies haven’t developed a new one in 30 years. That’s because drug development is extremely expensive and there’s little profit in the final product.

世界亟需新的抗生素,但是近30年医药公司在新药开发方面毫无建树。一方面是因为药品开发的成分非常高,另一方面是因为最终产品的利润微薄。

To address this, Pew Charitable Trusts, a public policy non-profit in Philadelphia, has developed the Shared Platform for Antibiotic Research and Knowledge (Spark). It’s a cloud-based, virtual library of antibiotic research data and analytics that scientists can use to work together on building new discoveries. “Similar data-sharing resources have successfully catalysed drug discovery in other research areas such as cancer, neglected tropical diseases, and tuberculosis,” says Kathy Talkington, director of the antibiotic resistance programme at Pew Charitable Trusts. “We hope that Spark will do the same for antibiotic-resistant bacteria. We expect it to be publicly available, and open for use by researchers from around the world, within the next year.”

为解决这一问题,位于费城的公共政策非营利机构皮尤慈善信托(Pew Charitable Trusts)建立了Spark平台(抗生素研究和知识共享平台)(Shared Platform for Antibiotic Research and Knowledge)。它是基于云服务的抗生素研究数据和分析的虚拟图书馆,科学家可以利用它来合作和探索。"类似的数据共享资源已经成功催生针对癌症、被忽视的热带疾病以及结核病等领域的药品开发。"皮尤慈善信托抗生素耐药性项目主管凯茜·托金顿(Kathy Talkington)说,"我们希望Spark平台能够找到方法杀死有抗生素耐药性的细菌。我们希望在明年年内公开研究成果,并开放给全世界的研究者使用。"

The hope is that allowing scientists to work across different disciplines, develop new methodologies for antibiotic discovery, and work within academia and the industry could be the key to ending the years-long drought in new antibiotic development.

他们希望让不同学科的科学家展开合作,开发探索抗生素的新方法。让学术界和医疗业展开合作有可能让抗生素新药开发久旱逢甘霖。

The US Centers for Disease Control (CDC) is also responding to the problem with a network of their own. Specifically, the Antibiotic Resistance Lab Network, which was developed in 2016, is boosting the organisation’s ability to detect antibiotic resistance whenever it shows itself – whether that be in healthcare, food, or community settings.

美国疾病管制与预防中心也建立了自己的网络以应对这一问题。具体是2016年建立的抗生素耐药性实验室网络(Antibiotic Resistance Lab Network)。它增强了组织检测抗生素耐药性的能力——不论它是出现在医疗业、食品业还是其他社会环境下。

With labs strategically placed around the United States, it tracks resistance trends and shares data with hospitals, doctors, and scientific institutions developing diagnostic tests and new treatments. In addition to these core labs, the CDC laboratories in all 50 states received additional funding to genetically test for a series of antibiotic resistant bacterium.

它在全美战略部署实验室,追踪耐药性趋势,与医院、医生、科研机构共享数据,开发诊断测试和新疗法。除了这些核心实验室之外,美国疾病管制与预防中心在50个州的实验室还获得额外的资金,对一系列有抗生素耐药性的细菌进行基因测试。

It’s a nationwide effort that pits knowledge and teamwork against the growing health crisis of antibiotic resistance.

这是一项全国层面的工作,集中知识和团队合作的力量,对抗日益加深的抗生素耐药性危机。

“The Antibiotic Resistance Laboratory Network (ARLN) increases our ability to detect and identify new resistant threats in the United States,” says Jean Patel, the science team lead of the Antibiotic Strategy and Coordination Unit. “Laboratories in this network are focusing on specific germ-testing that provides essential information to stop the spread of resistant infections.”

"抗生素耐药性实验室网络提高了对新的耐药性威胁的检测和识别能力。"抗生素战略和协调部的科学组负责人让•帕特尔(Jean Patel)说,"这个网络内的实验室正专注于具体的细菌测试,为停止耐药性感染的扩散提供重要信息。"

MAKING EXISTING ANTIBIOTICS STRONGER

增强现有抗生素的威力

Finally, one antibiotic, called vancomycin, has been used to treat infections for at least 60 years. It is considered a “last-resort” drug, used only when there are no other options, because it has avoided antibacterial resistance – until now.

最后,还有一种名为"万古霉素"的抗生素已经使用了至少60年。它被认为是最后的办法,只有在万不得已时才会使用,因为此前它都没有出现针对它的耐药性。

In recent years bacteria resistant to the drug have been discovered. In response to this scientists have been attempting to re-engineer the antibiotic to make it more powerful and more effective. They do this by changing its structure. So far there have been three modifications to the drug by scientists over the years. The most recent two, carried out by Dale Bolger and his team at the Scripps Research Institute in La Jolla, California, added additional mechanisms for the antibiotics to kill bacteria.

近些年来,有人发现这种药也出现了耐药性。为了应对这一情况,科学家尝试重新改造这一抗生素,通过改变其结构,增强药力和药效。到目前为止已经有了三种改良版万古霉素。最近的两种是加利福尼亚州拉霍亚(La Jolla)Scripps研究所的戴尔·博尔格(Dale Bolger)带领的团队研制。他们为这种抗生素增加了新的杀死细菌的机制。

“Each improved potency and each improved their durability toward resistance,” says Bolger. And resistance to the new strain, he says, will be much, much slower to develop. The first modification alone is “robust and could alone last 50 years in clinic. If bacteria devise a way to get around it they are still killed by the other two mechanisms and resistance would fail to propagate.” Work is currently being done to make the new version of the drug less complicated to manufacture.

"每一种改良的抗生素都提高了药力,并且改善了针对耐药性的持久力,"博尔格说。新菌株形成耐药性所需的时间要长很多。仅第一种改良版"就可以在临床环境下坚持50年。如果细菌形成耐药性,还有另外两种杀菌机制,耐药性就无法延续下去,"目前他的团队正在简化新版本抗生素的制造流程。

But Bolger says it is “exciting.” Eventually, having a reliable last-resort drug that is difficult for bacteria to resist could save many lives.

但是,博尔格说这项工作"让人激动"。因为最终将有一张可靠的最后的王牌让细菌难以产生耐药性,从而拯救很多人的生命。

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