關於抗生素的一條好消息

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.
耐受常用藥物治療的感染日漸增多，卻缺乏新型抗生素來替代那些不再有效的藥物，這已成爲全球亟待解決的問題。一種生產抗生素的特殊方法或可對此有所助益。

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.
研究人員在週三的《自然》(Nature)雜誌上報道，這種從生活在泥土裏的細菌中提取藥物的方法生產出了一種新的強力抗生素。在小鼠試驗中，這種新藥——teixobactin可以輕鬆治癒嚴重感染，且沒有出現副作用。

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，研究人員稱，這種藥物具有獨特的作用機理，使其幾乎不會引起細菌耐藥性。而且，這種生產藥物的方法或許還能成爲一把鑰匙，打開蘊藏着可抵抗感染和癌症的天然化合物大寶藏——要知道，在此之前，由於能產生這些化合物的微生物不能在實驗室中生長，科學家們對它們一直只能望而興嘆。

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尚未接受過人體試驗，因此它的安全性和有效性尚屬未知。該文章的責任作者，美國東北大學抗微生物藥物發現中心（Antimicrobial Discovery Center at Northeastern University，位於波士頓）主任基姆·劉易斯(Kim Lewis)稱，要展開人體研究大概還需要兩年左右。他還在上週二的電話新聞發佈會上說，這些研究將花費數年時間，所以即使該藥物通過了所有必需的測試，也還需要五六年的時間才能面世。如果能通過審批，他說，該藥物很可能採用注射給藥，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.
幾位未參與該研究的專家表示，這種用於分離藥物的技術具有巨大的潛力。他們還說，teixobactin看起來前途無量，但因爲畢竟它尚未經過人體試驗，他們也都表現出了謹慎的態度。

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.”
範德堡大學(Vanderbilt University)的傳染病專家威廉·沙夫納(William Schaffner)博士稱這項研究“新穎獨特”，並表示“我們迫切需要一些有關抗生素的好消息”。

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.”
至於teixobactin，他認爲：“它尚且處於實驗室和小鼠試驗水平，而小鼠距離人類還有很遠的距離，許多化合物都沒能成功跨越這一大步。”他又補充道：“毒性往往是藥物的‘阿喀琉斯之踵’（譯註：指致命弱點）。”

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.”
斯坦福大學(Stanford)的醫科教授大衛·A·瑞爾曼(David A. Relman)博士在一封電子郵件中寫道：“該研究揭示，微生物界可生產出豐富多樣的、我們尚未認識、且具有生物活性的強效化合物——其中的一些可能具有實際臨牀價值。”

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.
據美國疾病控制和預防中心(Centers for Disease Control and Prevention)的數據顯示，在美國，每年至少有200萬人感染耐藥菌，其中23000人因此死亡。世界衛生組織(World Health Organization)警告說，去年，此類感染在世界各地都有發生，許多疾病的耐藥菌株正在以比能剋制它們的新抗生素更快的速度不斷出現。衆多製藥公司紛紛放棄研製新的抗生素，將研發重點轉向了更有利可圖的其他類型的藥物，使得這一問題進一步地複雜化了。

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.
這項新研究建立在一個前提之上，即：地球上的一切——植物、土壤、人、動物——都充斥着在激烈的競爭中求生存的微生物。爲了牢牢抑制住自己的競爭對手，微生物們分泌出了生物武器：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.
沙夫納博士指出：“按照細菌那種繁殖方式，要是沒有一種自然機制來限制它們的增長，早在億萬年前它們就會覆蓋整個地球，把我們全都吃幹抹淨了。”

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.
數十年來，科學家們和製藥公司都在利用微生物這座天然兵工廠（這些微生物通常是從土壤樣本中發掘篩選而來），並發現了青黴素、鏈黴素、四環素等多種拯救了無數生命的抗生素，以及一些可用於治療癌症的強力化療藥物。然而，致病微生物開始對多種現有藥物產生耐藥性，要尋找替代性藥物，卻存在一個重大障礙，劉易斯博士解釋道：自然環境中約99%的微生物物種都無法在普通的實驗室條件下生長。

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.
劉易斯博士和他的同事們發現了一種可以培養這些微生物的方法。具體程序包括稀釋土壤樣本（生產出teixobactin的土壤樣本來自“緬因州的一片草地”），並將其放在專門的設備上。然後，就是成功的祕訣：將該設備放進滿滿一盒與樣本來源相同的土壤當中。

“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.
“從本質上講，我們是在糊弄那些細菌，”劉易斯博士說，讓它們以爲自己回到了家鄉的泥土中，於是就可以自然而然地分裂，生長成菌落。一旦形成菌落，代表這些細菌已經被“馴化”了，這時研究人員就可以將它們採集起來，開始在實驗室的培養皿中培養。

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.
這項研究由美國國立衛生研究院(National Institutes of Health)和德國政府（一部分共同作者在波恩大學[University of Bonn]工作）資助。東北大學對這種生產藥物的方法持有專利並將其授權給了一傢俬營公司NovoBiotic Pharmaceuticals（位於馬薩諸塞州劍橋市），該公司對使用該方法生產的任何化合物持所有權。劉易斯博士是該公司的有酬顧問。

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是研究人員從10000株細菌菌株中篩選分離出來的最有前途的候選藥物。在試管中，它可以殺死多種類型的葡萄球菌和鏈球菌，以及炭疽和結核病的病原體。在小鼠身上測試時，它可以清除鏈球菌感染和葡萄球菌，其中也包括耐藥菌株。它可以作用於一類被稱爲“革蘭氏陽性”的細菌，但對“革蘭氏陰性”細菌（如耐藥性肺炎、淋病、膀胱和血液感染的某些主要致病菌）無效。劉易斯博士表示，研究人員正試圖對該藥物進行改良，希望它也可以用來治療革蘭氏陰性菌感染。

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.
劉易斯博士說，他們還識別出了二十五種其他的候選藥物，但它們大多存在毒性或不溶性之類的缺點，但他也補充說，其中一種雖然有毒，但可能具有抗擊癌症的效果，他們將對其進行進一步的測試。

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與大多數抗生素的機理不同，它是通過阻斷脂肪分子，從而阻礙細菌細胞壁的合成來發揮作用的。研究人員表示，脂肪分子不容易發生變異，因此不容易令微生物產生耐藥性。劉易斯博士預言，假若確實會出現耐藥性，也將需要很長很長的時間。

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.
瑞爾曼博士認爲上述關於耐藥性的論述具有合理性。但他也警告說，有時候，“耐藥性會以出人意料的機制產生”，在藥物推廣的過程中仔細監測是發現它們的唯一方式。

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.
劉易斯博士表示，他希望這項研究能指引出一條尋找新型抗生素的新路。迄今爲止科學家們一直假設耐藥性的產生不可避免，唯一的解決辦法就是爭分奪秒地開發新的抗生素，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.”
“這項研究向我們提供了另一種策略，”他說，“開發不會引起耐藥性的化合物。”