【龙腾网】病毒是对抗超级细菌的最佳武器吗?噬菌体告诉你答案
Antibiotics won the battle against resistant bacteria, but they may not win the war.
抗生素曾赢得了对抗耐药细菌的战斗，但它们可能不能再赢得这场战争了。
You probably know that antibiotic-resistant bacteria, also known as superbugs, have hampered physicians’ ability to treat infections. You may also be aware that there has been a steep decline in the number of new antibiotics coming to market.
你可能知道耐抗生素细菌，也被称为超级细菌，已经阻碍了医生治疗感染的能力。你可能也意识到，市场上新抗生素的数量急剧下降。
Some headlines suggest humanity is doomed by antimicrobial resistance; even politicians and governments have weighed in, comparing rising antimicrobial resistance to other popular crises such as climate change. Although I believe these assertions are exaggerated, antimicrobial resistance is a serious problem.
一些头条新闻表明，人类注定要遭受抗生素耐药性;甚至政治家和政府也参与进来，将不断增长的抗生素耐药性与气候变化等其他常见危机进行了比较。尽管我认为这些断言有些夸张，但抗生素耐药性是一个严重的问题。
I am a physician scientist with a specialty in infectious diseases. I have been fascinated by the role that bacteria play in human health, and the potential for using viruses to treat bacterial infections.
我是一名医学科学家，专攻传染病。我一直着迷于细菌在人类健康中所扮演的角色，以及利用病毒治疗细菌感染的潜力。
What causes antimicrobial resistance?
是什么导致了抗生素耐药性?
One significant factor contributing to antimicrobial resistance is the excessive use of antibiotics. In the U.S., where antibiotics are widely available, some patients demand these drugs for many different illnesses. Many physicians appease their patients because they don’t understand when and when not to use them and because there is no regulatory structure to limit their use. Anyone with a prescription pad can prescribe any antibiotic to treat any condition and rarely, if ever, face any consequences. There are some efforts to reduce antibiotic use, but the scope of the problem in the U.S. remains large.
过度使用抗生素是造成抗生素耐药性的一个重要因素。在美国在美国，抗生素随处可见，一些病人需要这些药物治疗许多不同的疾病。许多医生安抚他们的病人，因为他们不知道什么时候不使用，什么时候不使用，也因为没有监管结构来限制他们的使用。任何拿着处方笺的人都可以用任何抗生素来治疗任何疾病，而且很少会面临任何后果。虽然已经采取了一些措施来减少抗生素的使用，但在美国，这个问题的范围仍然很大。
Some countries, such as Sweden, use incentives to encourage doctors to improve antibiotic uses. But there is no counterpart for this system in U.S. hospitals and clinics.
一些国家，如瑞典，使用激励措施来鼓励医生改进抗生素的使用。但在美国的医院和诊所里，还没有类似的系统。
The problem goes beyond humans; 70 percent of all antibiotics are actually used on animals. This means that humans can be exposed to antibiotics by just handling animal products. The drumstick you are preparing for dinner might also have antibiotic-resistant bacteria tagging along.
这个问题不仅限于人类;事实上，70%的抗生素都是用在动物身上的。这意味着人类只要接触动物产品就能接触到抗生素。你正在准备晚餐的鸡腿上也可能有耐抗生素细菌。
Once antimicrobial resistance develops in a bacterium, it doesn’t always go away. For example, methicillin-resistant Staphylococcus aureus (MRSA) evolved resistance to multiple different antibiotics; yet, despite efforts to reduce its spread by limiting the use of antibiotics that led to its emergence, MRSA still persists in hospitals and the community.
一旦细菌产生了抗菌素耐药性，它并不总是消失。例如，耐甲氧西林的金黄色葡萄球菌(MRSA)进化出对多种不同抗生素的耐药性;然而，尽管通过限制抗生素（导致MRSA出现）的使用来减少其传播，MRSA仍然在医院和社区中存在。
An alternative to antibiotics
抗生素的替代品
Another reason for finding alternatives to antibiotics is that we share our microbes with the people and pets who live around us; thus, others can acquire one of these superbugs without ever taking an antibiotic.
寻找抗生素替代品的另一个原因是，我们与生活在我们身边的人和宠物分享我们的微生物;因此，其他人无需服用抗生素就能感染这些超级细菌。
A not-so-obvious reason for developing new therapies is that our bodies are home to a large community of microorganisms, including bacteria, called our microbiome. These microorganisms are necessary to maintain our health. Those same antibiotics that kill harmful bacteria also kill the good ones.
开发新疗法的一个不太明显的原因是，我们的身体是一个大的微生物群落的家园，包括细菌，被称为我们的微生物群落。这些微生物是维持我们健康所必需的。杀死有害细菌的抗生素也会杀死有益细菌。
There is an alternative to antibiotics, but it was dismissed by medicine years ago.
有一种抗生素的替代品，但多年前被医学界所摒弃。
The original phage therapy story
最初的噬菌体治疗故事
That alternative was something called phage therapy, which uses viruses that infect bacteria, called bacteriophages, to kill disease-causing bacteria. Bacteriophages, or phages, were used frequently in the early- and pre- antibiotic eras between the 1920s and ‘40s to treat life-threatening infections.
另一种方法叫做噬菌体疗法，它使用感染细菌的病毒，即噬菌体，来杀死致病细菌。噬菌体，在20世纪20年代至40年代的早期和前抗生素时代被频繁地用于治疗危及生命的感染。
But phage therapy had many disadvantages. The first was that phages were unpredictable. One type of phage might wipe out the bad bacteria in one individual but not another’s. So hospitals had to keep a broad collection of phages to kill disease-causing bacteria from all their patients. An antibiotic such as vancomycin, by comparison, predictably kills entire groups of bacteria.
但是噬菌体疗法有很多缺点。首先，噬菌体是不可预测的。一种噬菌体可以消灭一个人体内的有害细菌，但不能消灭另一个人体内的。因此，医院不得不大量收集噬菌体，以杀死所有病人身上的致病细菌。相比之下，万古霉素等抗生素可预见地杀死整群细菌。
Another downside is that phage collections require maintenance. So not only did hospitals have to keep a large variety of phages on hand, but they had to keep them in shape. So medicine chose antibiotics for convenience, and hadn’t looked back in any meaningful way, until recently.
另一个缺点是噬菌体收集需要维护。因此，医院不仅要保存大量的噬菌体，而且还要保持它们的形状。所以医学为了方便而选择了抗生素，直到最近才以任何有意义的方式回顾过去。
Making a comeback?
So, why is phage therapy making a comeback? Antibiotic resistance is an obvious answer, but doesn’t explain the full story.
卷土重来?
那么，为什么噬菌体疗法会卷土重来呢?抗生素耐药性是一个显而易见的答案，但并不能解释全部情况。
As a specialist in infectious diseases, I have been interested in phage therapy as long as I can remember, but only recently have I felt comfortable saying this out loud. Why? A physician might be considered a “quack” just for mentioning phage therapy because the early attempts were neither a rousing success or a colossal failure. Like any therapeutic, it had its strengths and weaknesses.
作为一名传染病专家，我从记事起就对噬菌体治疗很感兴趣，但直到最近，我才觉得把这句话大声说出来很舒服。为什么?仅仅因为提到噬菌体治疗，医生就可能被认为是“江湖医生”，因为早期的尝试既没有令人振奋的成功，也没有巨大的失败。和任何治疗方法一样，它也有自己的优缺点。
However, now scientific advances can guide us toward which phage is best for destroying a particular microbe. With the rising antimicrobial resistance crisis, physicians and scientists have a well-timed opportunity to work together to develop effective phage therapies.
然而，现在科学的进步可以引导我们找到哪种噬菌体最适合消灭一种特定的微生物。随着抗生素耐药性危机的加剧，医生和科学家有了一个很好的时机来共同开发有效的噬菌体疗法。
The proof of this comes from recent landmark phage therapy cases. The successful treatment of a physician with a life-threatening infection and a grave prognosis caused by a multi-drug resistant bacterium at my institution serves as a great example. Another pivotal case circulating in popular media has kept this trend going. We physicians may be able to treat just about any disease-causing bacterium; it is just a matter of finding a suitable phage.
这一点的证据来自最近具有里程碑意义的噬菌体治疗案例。我所在的机构成功地治疗了一名因多重耐药细菌引起的危及生命的感染和严重预后的医生，这是一个很好的例子。另一个在大众媒体上流传的关键案例使这一趋势得以延续。我们医生也许能够治疗任何致病细菌；这只是找到一个合适的噬菌体的问题。
A big part of phage therapy research is devoted to “phage hunting,” where we microbiologists scour the soil, the oceans and the human body to identify phages with the potential to kill the bacteria that ail us. While the pace of these studies has been slow, the new research is revealing the therapeutic potential of phages in medicine.
噬菌体治疗研究的很大一部分致力于“噬菌体狩猎”，在那里，我们微生物学家仔细研究土壤、海洋和人体，以确定具有杀死困扰我们的细菌潜力的噬菌体。尽管这些研究进展缓慢，但新的研究揭示了噬菌体在医学上的治疗潜力。
You might think that with all the phage hunting and landmark cases that we would start using phage therapy all the time, but we don’t.
你可能认为在所有的噬菌体狩猎和具有里程碑意义的案例中，我们会一直使用噬菌体疗法，但我们没有。
The case for using phages
使用噬菌体的例子
One advantage of antibiotics is that since they have been used for decades, we know a lot about their safety. Physicians make simple calculations every day about the risk-benefit ratio of using antibiotics, but aren’t equipped to make the same calculations about phages. Does anyone really want a doctor injecting them with a virus to cure a bacterial infection? I doubt that would be anyone’s choice when the question is posed that way.
抗生素的一个优点是，由于它们已经使用了几十年，我们对它们的安全性有了很多了解。医生们每天都会对使用抗生素的风险-收益比进行简单的计算，但却没有能力对噬菌体进行相同的计算。真的有人想让医生给他们注射病毒来治疗细菌感染吗?当问题以这种方式提出时，我怀疑这不是任何人的选择。
But, remember that phages are natural. They’re on every surface of your body. They are in the ocean and soil, and in your toilet and sink. They are literally everywhere. Thus, putting a phage into your body to kill a bacterium quite frankly is something that nature does to us every single day, and as far as we know, we are no worse for the wear.
但是，请记住噬菌体是自然形成的。它们在你身体的每一个表面。它们在海洋和土壤里，在你的马桶和水槽里。它们确实无处不在。因此，将噬菌体放入体内杀死细菌是大自然每天都在做的事情，据我们所知，我们的身体并没有因此而受损。
Phages are estimated to kill half the world’s bacteria every 48 hours and are probably the most potent antibacterial agents out there. Is there really a compelling reason to be concerned when a doctor gives us a phage instead of us acquiring that same phage from our sink at home? Only time will tell. Unfortunately, as antimicrobial resistance continues to rise, time may not be on our side.
据估计，噬菌体每48小时就能杀死世界上一半的细菌，而且可能是最有效的抗菌剂。当医生给我们一种噬菌体而不是我们从家里的水槽中获得同样的噬菌体时，我们真的有一个令人信服的理由担心吗?只有时间才能证明。不幸的是，随着抗菌素耐药性继续上升，时间可能不会站在我们这一边。
（评论部分）
Jon Richfield
I am a great fan of phages and the potential for engineering them, using them not only against bacteria, but also fungi, and possibly even some of the larger viruses, but it seems to me that their use in combination with some of the antibacterial chemicals such as antibiotics, should be of interest as well.
For example, if an antibiotic excludes or reduces the risk of secondary infections while the phage controls a primary infection of plague or TB, or kills an emerging strain of antibiotic-resistant bacteria during phage treatment, that might be of value, shouldn’t it?
我非常喜欢噬菌体，和其工程改造的潜力，不仅可以对抗细菌，还可以对抗真菌，甚至可能是一些更大的病毒，但在我看来，它们与抗生素等抗菌化学物质的结合使用也应该引起人们的兴趣。
例如，如果一种抗生素排除或降低了继发性感染的风险，而噬菌体控制了鼠疫或结核病的一次感染，或者在噬菌体治疗期间杀死了一种新出现的耐抗生素细菌，这可能是有价值的，不是吗?
David Pride（作者回复）
加州大学圣地亚哥分校微生物学副主任
That is a major area of research in which phages are used. In fact, in a lot of phage studies, they are used in combination with antibiotics because the antibiotics are the standard of care. It can make it difficult to figure out how much improvement was seen due to the phage and how much of the improvement was due to the antibiotics.
这是噬菌体应用的一个主要研究领域。事实上，在许多噬菌体研究中，它们与抗生素结合使用，因为抗生素是治疗的标准。这使得我们很难弄清楚噬菌体的作用有多大，以及抗生素的作用有多大。
In a lot of the more recent cases, it is more obvious that the phage is moving the needle even if it is receiving an assist from the antibiotic. The immediate future of phage therapy will probably involve phages, antibiotics, and the human immune system, with the hope to eliminate the antibiotics from that equation
在最近的许多病例中，更明显的是噬菌体在移动针头，即使它得到了抗生素的帮助。在不久的将来，噬菌体治疗可能会涉及噬菌体、抗生素和人类免疫系统，希望将抗生素从这个等式中消除。
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Robert Ferguson
Thank you David; that is encouraging.
I remember reading about this c50years ago. It was pioneered in Russia, I believe. In Moscow they had a huge collection of specifis bacteriophage virus samples. It was the future, i believed then. WELL DONE RUSSIA!!!
谢谢你大卫，这是令人鼓舞的。我记得50年前读过这篇文章。我相信它是在俄罗斯开创的。在莫斯科，他们收集了大量的噬菌体病毒样本。我当时相信这就是未来。干得好俄罗斯！
David Pride（作者回复）
Yes. This geographic area was a hotbed of phage therapy research. The study of phage therapy continues in some Eastern European countries that were a part of the Soviet Union.
是的。这个地理区域是噬菌体治疗研究的温床。噬菌体疗法的研究仍在前苏联的一些东欧国家进行。
Robert Ferguson（回复楼上）
I used “Russia” because US people usually simplified USSR to that AND it was Moscow the “Ark” of viruses was held. 50 years ago? USA dates and progress then would be helpfull. I’ll do some research. Why, if US research on phages was so advanced and is now found to be efficacious potentially, was there not a massive progress made in that time in the most advanced and richest country ever?
我用“俄罗斯”是因为美国人通常把苏联简化成“俄罗斯”，而病毒的“方舟”就在莫斯科。50年前？美国的日期和进展将是有帮助的。我会做一些调查。如果美国对噬菌体的研究如此先进，而且现在被发现具有潜在的有效性，那么在那个有史以来最发达和最富有的国家，为什么没有取得巨大的进展吗?
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Alvaro Ferreira Junior
congratulations for your elegant text. I was surprised with high use of antibiotics in animals. I want to know your some opinion about the use of phages against bacteria in farm animals.
祝贺你优美的文字。我对动物中抗生素的大量使用感到惊讶。我还想知道你对在农场动物身上使用噬菌体对抗细菌有何看法。
