Elife:古生菌或可作为抗菌药来源

2014-11-28 王英 生物通

目前,最神秘的一种生命形式,被证明可能是一种丰富和尚未开发的抗菌药来源。这种神秘的生命形式就是古生菌(Archaea),是一个单细胞生物家族,生长在极端环境,例如沸腾的热液池和冒着烟的深海喷口,对于大多数其他物种来说,这些条件都过于极端。 美国范德堡大学生物科学副教授Seth Bordenstein带领了这项研究,他指出:“这是首次在古生菌中发现功能性的抗菌基因。你不能夸大人类

目前,最神秘的一种生命形式,被证明可能是一种丰富和尚未开发的抗菌药来源。这种神秘的生命形式就是古生菌(Archaea),是一个单细胞生物家族,生长在极端环境,例如沸腾的热液池和冒着烟的深海喷口,对于大多数其他物种来说,这些条件都过于极端。

美国范德堡大学生物科学副教授Seth Bordenstein带领了这项研究,他指出:“这是首次在古生菌中发现功能性的抗菌基因。你不能夸大人类正面临的抗生素耐药性问题的意义。这一发现应该有助于激励我们在这种尚待开发的生物中,开发新的抗生素。”

范德堡大学已经就新发现的这个基因申请了专利,正在探索产业合作伙伴及授权机会。

直到上世纪70年代末,生物学家认为,古生菌只是一种怪异的细菌,但是后来对它们DNA的一项里程碑分析表明,它们代表着生命进化树上一个独立的分支,可以追溯到30亿多年以前。

范德堡大学和波特兰州立大学的一个科学家小组,对不同物种之间广泛的水平基因转移进行了研究,发现古生菌可能是一个新的药物来源。

研究人员正在调查一个基因,这个基因可编码存在于眼泪、唾液、乳汁和粘液中的一种酶——溶菌酶。这种特殊的溶菌酶具有广谱抗菌作用,从细菌显著跃升到生命的各个主要分支。他们发现它有一个极不可能的来源:一种古生菌微生物,栖息在深海地区,周边有深海热泉喷涌出的过热矿泉水。

相关研究以“Antibacterial Gene Transfer Across the Tree of Life”为题,发表在2014年10月25日的新科学杂志 eLife ,详细描述了这一发现。作者包括范德堡大学博士研究生Jason Metcalf、Lisa Funkhouser-Jones和Bordenstein,博士后Kristen Brileya和波特兰州立大学教授Anna-Louise Reysenbach。

Bordenstein说:“我们发现,这种古生菌溶菌酶,可杀死厚壁菌的某些物种,厚壁菌是一大组细菌,包括经典的耐药菌金黄色葡萄球菌,可引起炭疽的芽孢杆菌和肠道感染菌艰难梭状芽胞杆菌。”

以前,科学家们在很大程度上不考虑将古生菌作为药物来源,因为它们不会引发任何人类疾病,专家认为它们与其他的生命形式并没有太多的相互作用,因为它们仅限于极端环境。

然而,近年来,研究人员发现,有相当数量的细菌与极端环境古生菌共存,古生菌自身不仅局限于这种环境,而且也生活在温和的环境中,如海藻类和哺乳动物肠道内。

Metcalf 说:“事实上,古生菌与其他形式的生命相互作用,远比我们想象的多,这意味着,它们在竞争资源。而且,如果它们竞争资源,那么它们就会产生化学物质来攻击和防御其他生物:这些化学物质可能有效地对抗我们目前抗生素的细菌耐药性。”

科学家第一次在一种攻击沃尔巴克氏体(Wolbachia,感染昆虫和世界其他无脊椎动物的一种细菌寄生虫)的噬菌体病毒中,发现了这种抗菌基因,编码GH25-muramidase。它是细菌中常见的一个酶家族中的成员,细菌用其来改造它们的细胞壁。噬菌体利用相同的酶,通过在它们的细胞壁上咬开孔洞,侵入细菌。

此外,该基因存在于昆虫(pea aphid,豌豆蚜)中,以前有过报道。但是当研究人员检查其进化史时,他们惊奇地发现,这个基因也突然出现在一种古老的植物谱系(江南卷柏Selaginella moellendorffii)和许多真菌物种中,包括米曲霉(用于亚洲烹饪以制造酱油、味噌和酒精饮料如清酒的一种霉菌)。

Metcalf说:“这完全是出乎意料的。但是,最古怪的事情发生在一种古生菌Aciduliprofundum boonei——生活在深海热泉群落。究竟为什么需要这样的一种酶呢?”

为了探讨这一问题,Metcalf找到了世界上专门收集和培养古生菌的少数科学家,包括A. boonei菌:波特兰州的Reysenbach实验室。在他们的帮助下,他能够提纯A. boonei的GH25-muramidase结构域,这是确定酶的作用所需要的一步。

Reysenbach说:“从生态学的角度来看,这些结果对我们来说真的很酷。这些古生菌与极端细菌生长的很靠近,在生物膜中,需要竞争资源。我常常在想,‘古生菌是如何做到的?’通过本文,我们发现,聪明的古细菌通过从其细菌‘配偶’和竞争对手那里窃取基因,做到这一点。这表明古生菌是有益的,至今仍是发展新抗菌药物相对未开发的靶标。”

Metcalf也花了两年多的时间,试图从携带该基因的植物和真菌中提纯这种酶,但没有成功。Bordenstein说:“这是不寻常的。纯化大的抗菌蛋白,可能非常困难。这是一个非常困难的多层面的项目。”

原始出处:

Metcalf JA1, Funkhouser-Jones LJ1, Brileya K2, Reysenbach AL2, Bordenstein SR1.Antibacterial gene transfer across the tree of life.Elife. 2014 Nov 25;3. doi: 10.7554/eLife.04266.

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    2015-06-13 膀胱癌
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    2015-07-27 clmlylxy
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    2014-11-30 lhlxtx

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Nature:有关地球上生命的“二类别”观点受到支持

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