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.
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.
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.
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尚未同意过人体试验，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，坐落于波士顿）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媒体发布会上说，这类研究将花费数年时间，所以即便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问世。假如能通过审批，他说，该药物非常可能使用注射给药，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.
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“大家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.”
Dr. David A. Relman, a professor of medicine at Stanford, said by email, “It illustrates the amazing wealth and persity 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，微生物界可生产出多姿多彩的、大家尚未认识、且具备生物活性的强效化合物——其中的一些可能具备实质临床价值。”
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，很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。海量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种类的药物，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.
“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.
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.
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.
“Essentially, we’re tricking the bacteria,” Dr. Lewis said. Back in their native dirt, they pide 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.
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（一部分一同作者在波恩大学[University of Bonn]工作）资助。东北大学对这种生产药物的办法持有专利并将其授权给了一家私营公司NovoBiotic Pharmaceuticals（坐落于马萨诸塞州剑桥市），该公司对用该办法生产的任何化合物持所有权。刘易斯博士是该企业的有酬顾问。
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.
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.
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.
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.
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.
“This gives us an alternative strategy,” he said. “Develop compounds to which resistance will not develop.”