听，细菌在唱歌！ 新型抗生素-阻断信号

今天看到一篇关于群体效应的文献，挺有意思的，看来做科研还是要多思考多创新，发散思维很重要！

Blocking bacterial communication may help to fight infections
阻断细菌间的信息交流有可能对抗感染起到帮助

BACTERIA communicate with their neighbours through chemical signals. They use the information thus gathered to direct their behaviour, working as individual cells when they are at low density and then switching to more collaborative group behaviour at higher densities. It is when they are hunting as a pack that bacteria are particularly dangerous, for it is then that disease-causing microbes become powerful enough to attack living tissue and to fend off many sorts of antibiotic that would kill them individually.
细菌通过化学信号与周围的细菌进行联系。它们通过从周围收集来的信息来指导其行动，即当菌体密度低的时候，细菌多选择独自行动，而当菌体密度高的时候，细菌就会倾向群体合作活动。病原微生物成群地攻击活体组织是尤为危险的，当针对病原微生物个体有效的抗生素面对大量的病原体的抵抗时，也会失去应有的效用。

A number of chemists are looking for ways to jam this “quorum sensing” system with modified versions of the bacteria's own chemicals that will gum up the receptors for these signals. In particular, they hope to break down the collective defence against antibiotics. One group, led by Helen Blackwell, of the University of Wisconsin, Madison, has just reported its latest results to the American Chemical Society meeting in San Francisco.
许多化学家正在尝试利用修饰过的细菌信号分子占据菌体上相应的信号受体，来堵塞这种“群体感应”。换而言之，化学家们希望打破病原体针对抗生素的联合防御。一个由，麦迪逊，威斯康辛大学的Helen Blackwell所带领的团队在旧金山召开的美国化学学会发表了该研究最新的进展。

Dr Blackwell studies a group of quorum-sensing molecules called acylated homoserine lactones (AHLs). Many bacteria secrete AHLs, and simultaneously absorb them from their surroundings. As more bacteria grow in an area, the amount of AHL increases, eventually reaching a concentration high enough to trigger behavioural changes. For example, when a pathogenic bacterium called Pseudomonas aeruginosa reaches a quorum, it starts to produce molecules called virulence factors that damage the cells of its host, liberating their contents so that the bacteria can feed. The bacteria also band together tightly in response to the appropriate AHL, and secrete a protective layer of complex sugar molecules that protect them from their surroundings. The result, known as a biofilm, is the source of many hospital-based infections, since biofilms are impervious to antibiotics.
Blackwell博士研究了群体感应中的一种叫做酰基高丝氨酸内酯（AHLs）分子。许多细菌分泌该物质，并且与此同时从周围的环境中吸收这种物质。由于一个部位细菌聚集地越多，AHL分泌地越多，最终其浓度将升高以达到激发群体效应。例如，当一种病原菌，绿脓杆菌当达到群体感应的阶段时，就会释放破坏宿主细胞的毒力因子，通过使宿主细胞破裂来使细菌得到更多的营养物质。在AHL的作用下，细菌甚至还会紧紧聚集在一起并分泌一种复杂的糖质保护膜分布于其周围。由于这种被称作“生物膜”的物质可以抵御抗生素，结果因此导致了许多医源性感染。

Dr Blackwell's group has built up “libraries” of several hundred AHLs, and has been screening them in laboratory cultures to test their effects on various species of bacteria. One aim of this screening is to find compounds that block communication in some species but leave others undisturbed. That is important, because not all bacteria that live in people are harmful. Indeed, some are beneficial.
Blackwell博士的团队通过在实验室的环境下，检验AHL对不同菌种的影响，已建立起数百个AHL分子的数据库。这些工作唯一的目的就是，找出能阻断默写病原菌彼此信息交流而不干扰其它菌群的化合物。这很重要，因为栖居人体体内的不都是有害菌群，甚至一些对人体极其有益。

But stopping communication in a Petri dish is not the same as blocking it in a bacterium's natural environment. To find out if the new compounds can alter the course of infection in an animal, Dr Blackwell's group infected some cabbage white butterfly caterpillars with P. aeruginosa. Some of the caterpillars also received what she hoped was an appropriate AHL. After a week, nearly all of the animals infected with the bacteria alone were dead, whereas half of those that had been treated with the AHL survived.
但在细菌培养皿中阻断其信息交流与自然环境中（人体中）有着很大的不同。Blackwell通过对绿脓杆菌感染的菜白蝶幼虫进行试验，来检验这些新的化合物是否能改变动物感染的进程。一些有种被注入适量的“AHL”（此处为修饰过的）。一周后，几乎所有只感染细菌的动物都死了，被注入“AHL”的动物幸存了一半。

The new compounds are not yet ready for testing on people, according to Dr Blackwell. The dose rate needed to make them work in insects would be too much for people to tolerate, so some more design work is necessary. But if that can be done successfully, her first experiment will be to see—initially in mice—whether they can prevent burns from becoming infected.
据Blackwell表示，这种新的化合物还没有准备用于人体。对昆虫有效的剂量对人来说可能超过人的承受力，所以进一步研究工作势在必行。如果进一步实验顺利的话，小鼠将成为下一个动物模型，不知它们能不能躲过病原体感染这一劫呢？

Nor is suppressing bacteria the only possible use of AHLs. In at least one bacterium, Dr Blackwell and her fellow researchers are working on a way to turn up the volume instead of turning it down. Leguminous plants, such as peas and beans, rely on bacteria in their roots to “fix” atmospheric nitrogen into ammonia. Plants use this ammonia to make proteins. However, bacteria fix the gas only when their population is high enough to trigger the quorum-sensing machinery. One compound synthesised by Dr Blackwell's team is more effective than the natural signalling chemical at turning on this group behaviour—and works even when there are not enough bacteria around to induce the process naturally. Who could have guessed that bacteria would listen so well?
抑制细菌并不是AHL的唯一用途。在不止一种细菌上，Blackwell博士的团队发现了升高而不是降低AHL量的方法。如大豆和豌豆，这些豆科植物需要其根部的细菌（根瘤菌）将大气中的氮素转化为氨水供其吸收。同时，植物为细菌制造蛋白质。然而，只有在细菌（根瘤菌）达到一定数量时引发群体感应机制才能进行固氮。Blackwell博士的团队，人工合成了一种比自然激发群体行为的信号物质更为有效的化合物，甚至在菌体密度还不够高的时候就能让其进行固氮作用。谁能想到细菌会这么听话呢？