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An unusual method for producing antibiotics may help to solve an urgent global problem: the rise in infections that resist treatment with commonly used drugs, and the lack of new antibiotics to replace ones that no longer work.
耐受常用药物治疗的感染日渐增多，却缺乏新型抗生素来替代那些不再有效的药物，这已成为全球亟待解决的问题。一种生产抗生素的特殊方法或可对此有所助益。
The method, which extracts drugs from bacteria that live in dirt, has yielded a powerful new antibiotic, researchers reported in the journal Nature on Wednesday. The new drug, teixobactin, was tested in mice and easily cured severe infections, with no side effects.
研究人员在周三的《自然》(Nature)杂志上报道，这种从生活在泥土里的细菌中提取药物的方法生产出了一种新的强力抗生素。在小鼠试验中，这种新药——teixobactin可以轻松治愈严重感染，且没有出现副作用。
Better still, the researchers said, the drug works in a way that makes it very unlikely that bacteria will become resistant to it. And the method developed to produce the drug has the potential to unlock a trove of natural compounds to fight infections and cancer — molecules that were previously beyond scientists’ reach because the microbes that produce them could not be grown in the laboratory.
更妙的是，研究人员称，这种药物具有独特的作用机理，使其几乎不会引起细菌耐药性。而且，这种生产药物的方法或许还能成为一把钥匙，打开蕴藏着可抵抗感染和癌症的天然化合物大宝藏——要知道，在此之前，由于能产生这些化合物的微生物不能在实验室中生长，科学家们对它们一直只能望而兴叹。
Teixobactin has not yet been tested in humans, so its safety and effectiveness are not known. Studies in people will not begin for about two years, according to Kim Lewis, the senior author of the article and director of the Antimicrobial Discovery Center at Northeastern University in Boston. Those studies will take several years, so even if the drug passes all the required tests, it still will not be available for five or six years, he said during a telephone news conference on Tuesday. If it is approved, he said, it will probably have to be injected, not taken by mouth.
Teixobactin尚未接受过人体试验，因此它的安全性和有效性尚属未知。该文章的责任作者，美国东北大学抗微生物药物发现中心（Antimicrobial Discovery Center at Northeastern University，位于波士顿）主任基姆·刘易斯(Kim Lewis)称，要展开人体研究大概还需要两年左右。他还在上周二的电话新闻发布会上说，这些研究将花费数年时间，所以即使该药物通过了所有必需的测试，也还需要五六年的时间才能面世。如果能通过审批，他说，该药物很可能采用注射给药，而非口服。
Experts not involved with the research said the technique for isolating the drug had great potential. They also said teixobactin looked promising, but expressed caution because it has not yet been tested in humans.
几位未参与该研究的专家表示，这种用于分离药物的技术具有巨大的潜力。他们还说，teixobactin看起来前途无量，但因为毕竟它尚未经过人体试验，他们也都表现出了谨慎的态度。
Dr. William Schaffner, an infectious disease specialist at Vanderbilt University, called the research “ingenious” and said “We’re in desperate need of some good antibiotic news.”
范德堡大学(Vanderbilt University)的传染病专家威廉·沙夫纳(William Schaffner)博士称这项研究“新颖独特”，并表示“我们迫切需要一些有关抗生素的好消息”。
Regarding teixobactin, he said: “It’s at the test-tube and the mouse level, and mice are not men or women, and so moving beyond that is a large step, and many compounds have failed.” He added, “Toxicity is often the Achilles’ heel of drugs.”
至于teixobactin，他认为：“它尚且处于实验室和小鼠试验水平，而小鼠距离人类还有很远的距离，许多化合物都没能成功跨越这一大步。”他又补充道：“毒性往往是药物的‘阿喀琉斯之踵’（译注：指致命弱点）。”
Dr. David A. Relman, a professor of medicine at Stanford, said by email, “It illustrates the amazing wealth and diversity of as-yet-unrecognized, potent, biologically-active compounds made by the microbial world — some of which may have real clinical value.”
斯坦福大学(Stanford)的医科教授大卫·A·瑞尔曼(David A. Relman)博士在一封电子邮件中写道：“该研究揭示，微生物界可生产出丰富多样的、我们尚未认识、且具有生物活性的强效化合物——其中的一些可能具有实际临床价值。”
Drug-resistant bacteria infect at least 2 million people a year in the United States and kill 23,000, according to the Centers for Disease Control and Prevention. The World Health Organization warned last year that such infections were occurring all over the world, and that drug resistant strains of many diseases were emerging faster than new antibiotics could be made to fight them. Compounding the problem is the fact that many drug companies backed away from trying to develop new antibiotics in favor of other, more profitable, types of drugs.
据美国疾病控制和预防中心(Centers for Disease Control and Prevention)的数据显示，在美国，每年至少有200万人感染耐药菌，其中23000人因此死亡。世界卫生组织(World Health Organization)警告说，去年，此类感染在世界各地都有发生，许多疾病的耐药菌株正在以比能克制它们的新抗生素更快的速度不断出现。众多制药公司纷纷放弃研制新的抗生素，将研发重点转向了更有利可图的其他类型的药物，使得这一问题进一步地复杂化了。
The new research is based on the premise that everything on earth — plants, soil, people, animals — is teeming with microbes that compete fiercely to survive. Trying to keep one another in check, the microbes secrete biological weapons: antibiotics.
这项新研究建立在一个前提之上，即：地球上的一切——植物、土壤、人、动物——都充斥着在激烈的竞争中求生存的微生物。为了牢牢抑制住自己的竞争对手，微生物们分泌出了生物武器：抗生素。
“The way bacteria multiply, if there weren’t natural mechanisms to limit their growth, they would have covered the planet and eaten us all eons ago,” Dr. Schaffner said.
沙夫纳博士指出：“按照细菌那种繁殖方式，要是没有一种自然机制来限制它们的增长，早在亿万年前它们就会覆盖整个地球，把我们全都吃干抹净了。”
Scientists and drug companies have for decades exploited the microbes’ natural arsenal, often by mining soil samples, and discovered lifesaving antibiotics like penicillin, streptomycin and tetracycline, as well as some powerful chemotherapy drugs for cancer. But disease-causing organisms have become resistant to many existing drugs, and there has been a major obstacle to finding replacements, Dr. Lewis said: About 99 percent of the microbial species in the environment are bacteria that do not grow under usual laboratory conditions.
数十年来，科学家们和制药公司都在利用微生物这座天然兵工厂（这些微生物通常是从土壤样本中发掘筛选而来），并发现了青霉素、链霉素、四环素等多种拯救了无数生命的抗生素，以及一些可用于治疗癌症的强力化疗药物。然而，致病微生物开始对多种现有药物产生耐药性，要寻找替代性药物，却存在一个重大障碍，刘易斯博士解释道：自然环境中约99%的微生物物种都无法在普通的实验室条件下生长。
Dr. Lewis and his colleagues found a way to grow them. The process involves diluting a soil sample — the one that yielded teixobactin came from “a grassy field in Maine” — and placing it on specialized equipment Then, the secret to success is putting the equipment into a box full of the same soil that the sample came from.
刘易斯博士和他的同事们发现了一种可以培养这些微生物的方法。具体程序包括稀释土壤样本（生产出teixobactin的土壤样本来自“缅因州的一片草地”），并将其放在专门的设备上。然后，就是成功的秘诀：将该设备放进满满一盒与样本来源相同的土壤当中。
“Essentially, we’re tricking the bacteria,” Dr. Lewis said. Back in their native dirt, they divide and grow into colonies. Once the colonies form, Dr. Lewis said, the bacteria are “domesticated,” and researchers can scoop them up and start growing them in petri dishes in the laboratory.
“从本质上讲，我们是在糊弄那些细菌，”刘易斯博士说，让它们以为自己回到了家乡的泥土中，于是就可以自然而然地分裂，生长成菌落。一旦形成菌落，代表这些细菌已经被“驯化”了，这时研究人员就可以将它们采集起来，开始在实验室的培养皿中培养。
The research was paid for by the National Institutes of Health and the German government (some co-authors work at the University of Bonn). Northeastern University holds a patent on the method of producing drugs and licensed the patent to a private company, NovoBiotic Pharmaceuticals, in Cambridge, Mass., which owns the rights to any compounds produced. Dr. Lewis is a paid consultant to the company.
这项研究由美国国立卫生研究院(National Institutes of Health)和德国政府（一部分共同作者在波恩大学[University of Bonn]工作）资助。东北大学对这种生产药物的方法持有专利并将其授权给了一家私营公司NovoBiotic Pharmaceuticals（位于马萨诸塞州剑桥市），该公司对使用该方法生产的任何化合物持所有权。刘易斯博士是该公司的有酬顾问。
Teixobactin is the most promising candidate isolated from 10,000 strains of bacteria that the researchers screened. In test tubes, it killed various types of staph and strep, as well as anthrax and tuberculosis. Tested in mice, it cleared strep infections and staph, including a strain that was drug-resistant. It works against bacteria in a group known as “Gram-positive,” but not against microbes that are “Gram-negative,” which include some that are major causes of drug resistant pneumonia, gonorrhea and infections of the bladder and bloodstream. Dr. Lewis said researchers were trying to modify the drug to make it work against Gram-negative infections.
Teixobactin是研究人员从10000株细菌菌株中筛选分离出来的最有前途的候选药物。在试管中，它可以杀死多种类型的葡萄球菌和链球菌，以及炭疽和结核病的病原体。在小鼠身上测试时，它可以清除链球菌感染和葡萄球菌，其中也包括耐药菌株。它可以作用于一类被称为“革兰氏阳性”的细菌，但对“革兰氏阴性”细菌（如耐药性肺炎、淋病、膀胱和血液感染的某些主要致病菌）无效。刘易斯博士表示，研究人员正试图对该药物进行改良，希望它也可以用来治疗革兰氏阴性菌感染。
Twenty-five other drug candidates were also identified, but most had drawbacks like toxicity or insolubility, Dr. Lewis said, adding that one, though toxic, may work against cancer and will be tested further.
刘易斯博士说，他们还识别出了二十五种其他的候选药物，但它们大多存在毒性或不溶性之类的缺点，但他也补充说，其中一种虽然有毒，但可能具有抗击癌症的效果，他们将对其进行进一步的测试。
Teixobactin attacks bacteria by blocking fatty molecules needed to build cell walls, which is different from the way most antibiotics work. Those molecules are unlikely to change and make the microbes resistant, the researchers said. But if resistance does occur, Dr. Lewis predicted, it will take a long time to develop.
Teixobactin与大多数抗生素的机理不同，它是通过阻断脂肪分子，从而阻碍细菌细胞壁的合成来发挥作用的。研究人员表示，脂肪分子不容易发生变异，因此不容易令微生物产生耐药性。刘易斯博士预言，假若确实会出现耐药性，也将需要很长很长的时间。
Dr. Relman said the argument against resistance was reasonable. But he cautioned that “unsuspected mechanisms of resistance” sometimes develop, and that the only way to tell would be to monitor carefully what happens as the drug is used more and more.
瑞尔曼博士认为上述关于耐药性的论述具有合理性。但他也警告说，有时候，“耐药性会以出人意料的机制产生”，在药物推广的过程中仔细监测是发现它们的唯一方式。
Dr. Lewis said he hoped the research would point the way to a new approach to searching for novel antibiotics. Until now, he said, scientists have assumed that resistance would inevitably develop, and that the only solution would require scrambling to develop new antibiotics in hopes of keeping up.
刘易斯博士表示，他希望这项研究能指引出一条寻找新型抗生素的新路。迄今为止科学家们一直假设耐药性的产生不可避免，唯一的解决办法就是争分夺秒地开发新的抗生素，期望可以跟上菌株演化的速度。
“This gives us an alternative strategy,” he said. “Develop compounds to which resistance will not develop.”
“这项研究向我们提供了另一种策略，”他说，“开发不会引起耐药性的化合物。”
