超级细菌没得治?25岁华裔女博士发明了一种利器!

2016-09-27 应雨妍 奇点

意大利神经外科医生塞尔吉奥卡纳维洛(SergioCanavero)称脊髓修复方法或能使明年进行人类头部移植成为可能。近日《国际神经外科》发表了一篇文章及视频,一只脊髓严重损伤(几乎完全切断)的小狗在脊髓断裂间隙注入“胶水”药剂三周后“奇迹般地”恢复行走能力。意大利神经外科医生塞尔吉奥卡纳维洛(Sergio Canavero)称上述治疗小狗的脊髓修复方法或能使明年进行人类头部移植成为可能。不过这却引

88年前,苏格兰的细菌学家首次发现了青霉素,那个时候,它有一个“洋气”的名字,叫做“盘尼西林”。恰逢二战开始,于是青霉素在这场战争中拯救了无数士兵和百姓的生命。那时,它被称为“救命药”,和原子弹、雷达并称为“二战三大发明”。



二战时期的画报“感谢盘尼西林!他能够活着回家了!”

这一发现为我们拉开了“抗生素时代”的序幕,在那之后,科学家们陆陆续续地又发现了链霉素、红霉素、卡那霉素和万古霉素等等许多种抗生素。这些抗生素在过去的几十年里让许多本可能因细菌感染而“挂掉”的人们死里逃生,但是随着抗生素的滥用,本来捅出去的刀子却反过来捅了我们自己!

“超级细菌”的出现,更是让许多研究人员意识到,抗生素的压制地位正在减弱。为了避免将来有一天,人们要回忆起“被超级细菌支配的恐惧”,许多相关领域的研究人员都在努力研究能够克制超级细菌的药物。刚好,最近就有一个新的研究让人精神一振,墨尔本大学的一个研究团队合成了一种星形的肽类聚合物,能够高效地解决超级细菌!



星形聚合肽

为什么说是让人精神一振呢?首先,在过去的30年中,只有两种新型抗生素出现;其次,我们过去真的对细菌需要多久出现耐药性这个问题“一无所知”。不过现在,这个问题也有答案了!9月9日的《科学》杂志上,来自哈佛大学Roy Kishony团队的科学家们为我们展示了细菌变异的惊人速度![1]

研究人员在实验室中放置了一个60cm*120cm的“巨大培养皿”,培养皿中有14L的琼脂,它们是细菌的食物,研究人员把这个培养皿称为“MEGA-plate”。培养皿的两端没有抗生素,抗生素的浓度是阶梯式向中间升高的,分别是细菌不能生长的最低浓度,最低浓度的10倍、100倍,最中心是1000倍,所以培养皿的中心就是细菌的“终极目的地”,也理应是它们的“修罗地狱”!



培养基浓度设置

研究人员把初代的大肠杆菌放置在没有抗生素的边缘,让它们向中间生长。他们发现,大肠杆菌生长到最低浓度区域边界的时候暂时停止了,这时候它们并不是真的被抗生素阻挡住了,而其实是在“憋大招”。

果然,两天之后,有一部分“排头兵”突破了最低浓度的防线,开始发生了变异,也就是说,只用了两天,大肠杆菌就有耐药性了!那么高浓度的抗生素能不能让我们放心呢?显然事实没有那么乐观,在初具耐药性之后,新的变异很快出现,10倍的最低浓度也已经阻挡不住大肠杆菌前进的脚步了。逐渐地,它们来到了“地狱模式”的1000倍地区,而从“0”开始的这一过程只用了9天的时间(220小时)。

看到这里,我已经可以毫不意外地说,大肠杆菌会是这场“比拼”的胜利者,1000倍的浓度恐怕根本不能阻挡它们。事实证明,44个小时之后,它们就占领了1000倍浓度的区域。至此,抗生素大军一败涂地!

虽然这并不是在人体内的完美模拟,但是这个实验还是向我们传达了一个信息:10天左右的时间,大肠杆菌就产生了可以对抗1000倍致死浓度的抗生素的变异!这个数字多么的不可思议啊,如此快速的变异速度,如果没有好的办法对抗它们,那么用不了许多年,又会有很多人死于严重的、无法控制的感染。

正是有这样强有力的威胁,我们前面所提到的研究才显得尤其重要。这篇重要的研究发表在了《自然 微生物》杂志上,论文的第一作者是年仅25岁的华裔女博士Shu Lam,她与工程系的研究团队合作,合成了一种结构性纳米抗菌聚合肽(SNAPP)。它在遭遇超级细菌时,能够“牢牢地抓住细菌细胞的细胞壁,然后把它撕碎”,失去了细胞壁的保护,细菌变得非常脆弱,无法再适应体内环境,很快就会“一命呜呼”了。[2]



Shu Lam

Lam的团队对6种不同的“超级细菌”分别进行了体外实验,其中有一种是抗粘杆菌素的。粘杆菌素(colistin)曾经被誉为“抗生素的最后一道防火墙”,而在今年,能够抵抗它的细菌也出现了,也就是说,“最后一道防火墙”也被击破了!好在实验结果显示,这6种超级细菌全部阵亡,无一幸存。而且他们发现,与遭遇抗生素时的“拼死抵抗”不同,这些强悍的超级细菌被SNAPP撕碎了细胞壁后完全没有任何抵抗的迹象,迅速地结束了自己的“菌生”。Lam做出的猜测可能是细胞壁被破坏后,无规则的离子运动穿过了细胞的膜结构,启动了某个细胞凋亡信号通路,所以才有了“完全无抵抗”这一现象。


细菌细胞壁被破坏

可能有人会有疑问,这么简单的原理难道过去就没有类似的发现吗?其实,过去也有研究人员尝试用“抗菌肽”来杀死细菌,他们成功了,可与此同时,抗菌肽会“无差别攻击”,人体内的红细胞就成了“炮灰”,这样的损伤对于人体来说也是难以承受的。因此,Lam对此十分在意,他们的团队使用的SNAPP是蛋白质的大型复链,约有10纳米大小,是其他抗菌肽的几倍,是个十足的“大块头”,对于周围的包括红细胞在内的细胞都没有伤害。

这一点在小鼠实验中得到了验证,以能够杀死细菌的浓度为标准,当计量增加到100倍时,才有红细胞受到攻击。也就是说,SNAPP的相对安全性是非常高的,Lam的导师Greg Qiao教授认为,这是这个发现中,最了不起的一点。



Lam的导师Greg Qiao教授

对于Lam来说,这只是一个初步的结果,她对无抵抗的原因猜测的对不对?除了这6中之外其他的超级细菌能不能被杀死?在人体内的安全剂量又是多少?还有许许多多的疑问需要后续的实验去解决,但是毫无疑问,他们确实解锁了一种新的对付耐药细菌的方法,也是“疲软的”抗生素研发领域的一剂强心针,我们也期待着后续更加清楚明白的研究。

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    2016-11-19 qblt
  3. 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content=赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:25:05 CST 2016, time=2016-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=136625, encodeId=d3c413662511, content=继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=12, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:57 CST 2016, time=2016-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=136624, encodeId=476713662472, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:20 CST 2016, time=2016-09-27, status=1, ipAttribution=)]
    2016-12-16 为了宝宝

    超级细菌………

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1645864, encodeId=27031645864cf, content=<a href='/topic/show?id=85f04459592' target=_blank style='color:#2F92EE;'>#女博士#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44595, encryptionId=85f04459592, topicName=女博士)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9d1e23248319, createdName=gaoxiaoe, createdTime=Thu Jul 20 07:27:00 CST 2017, time=2017-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1683324, encodeId=79be16833244b, content=<a href='/topic/show?id=40c23592e38' target=_blank style='color:#2F92EE;'>#华裔#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=35927, encryptionId=40c23592e38, topicName=华裔)], attachment=null, authenticateStatus=null, createdAvatar=null, 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content=赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:25:05 CST 2016, time=2016-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=136625, encodeId=d3c413662511, content=继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=12, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:57 CST 2016, time=2016-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=136624, encodeId=476713662472, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:20 CST 2016, time=2016-09-27, status=1, ipAttribution=)]
    2016-10-12 ylzr123

    拜读了,受益匪浅,点个赞!

    0

  5. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:20 CST 2016, time=2016-09-27, status=1, ipAttribution=)]
    2016-10-09 ylzr123

    学习了,文章有深度,值得探究。

    0

  6. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:20 CST 2016, time=2016-09-27, status=1, ipAttribution=)]
    2016-10-01 ylzr123

    赞一个!好文章拜读了,认真学习了。

    0

  7. 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  8. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:20 CST 2016, time=2016-09-27, status=1, ipAttribution=)]
    2016-09-27 知难而进

    赞一个!

    0

  9. 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content=赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:25:05 CST 2016, time=2016-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=136625, encodeId=d3c413662511, content=继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=12, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:57 CST 2016, time=2016-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=136624, encodeId=476713662472, content=谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Tue Sep 27 22:24:20 CST 2016, time=2016-09-27, status=1, ipAttribution=)]
    2016-09-27 知难而进

    继续关注!

    0

  10. 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    2016-09-27 知难而进

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