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.
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.
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.
USING BACTERIA AGAINST ITSELF
If drugs fail, why not fight fire with fire?
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.
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.
“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.
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.
DEPLOYING TINY SEMICONDUCTORS
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.
“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.
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).
They could theoretically be so effective, that they would only require a one million-times smaller dose than traditional drugs.
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.
“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.”
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.
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.
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.
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
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.
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.
BRIDGING ACADEMIA AND INDUSTRY
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.
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.
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.
It’s a nationwide effort that pits knowledge and teamwork against the growing health crisis of antibiotic resistance.
“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.”
MAKING EXISTING ANTIBIOTICS STRONGER
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.
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.
But Bolger says it is “exciting.” Eventually, having a reliable last-resort drug that is difficult for bacteria to resist could save many lives.