美國科學(xué)家通過對噬菌體進(jìn)行改造,，使其能夠抑制細(xì)菌對抗生素的耐受性,。如果將其與抗生素聯(lián)合使用,，還能殺死目前已存在的對抗生素廣泛耐受的細(xì)菌。
噬菌體是一類寄生并侵害細(xì)菌的病毒,，又稱細(xì)菌病毒,。利用感染和殺死細(xì)菌的病毒來戰(zhàn)勝傳染的理念可以追溯到大約100年前。但這種療法從未曾在西方使用,，當(dāng)抗生素登上歷史的舞臺,，噬菌體療法更受冷落。
不斷有細(xì)菌對抗生素產(chǎn)生抗藥性,，迫使研究人員不斷研發(fā)新藥物來對抗這些細(xì)菌,。在以前的“噬菌體療法”中，噬菌體殺死細(xì)菌并且釋放更多的噬菌體尋找新的宿主,，但處于這種直接進(jìn)攻下的細(xì)菌很快會進(jìn)化并且對噬菌體產(chǎn)生抵抗力,。
美國波士頓大學(xué)的生物工程學(xué)家詹姆斯·柯林斯和其學(xué)生狄莫西·魯通過改造噬菌體使細(xì)菌更加脆弱，從而讓抗生素更容易奏效,。
柯林斯和魯使用基因工程技術(shù)改造了一個(gè)名叫M13的噬菌體,，該噬菌體在感染細(xì)菌時(shí)，會產(chǎn)生名為lexA3的細(xì)菌蛋白,，該蛋白可以損害細(xì)菌修復(fù)受損的DNA的能力,。當(dāng)修改后的M13噬菌體感染細(xì)菌，比如大腸埃希氏菌時(shí),，它產(chǎn)生lexA3,，讓大腸埃希氏菌更容易受到損害細(xì)菌DNA的藥物的攻擊。
研究人員發(fā)現(xiàn),，噬菌體增加了抗生素沃氟沙星殺死大腸埃希氏菌的能力,，即使該細(xì)菌對抗生素產(chǎn)生一定的抵抗力也如此。該發(fā)現(xiàn)表明,，這類噬菌體療法能夠恢復(fù)以往已被認(rèn)為不再起作用的抗生素的活力,。
在老鼠身上進(jìn)行的實(shí)驗(yàn)也得到了令人振奮的結(jié)論：在遭遇大腸埃希氏菌感染時(shí)，接受了沃氟沙星和修改后的M13噬菌體的老鼠,，有80%%存活下來,，而僅僅接受了抗生素的老鼠的存活率只有20%%。
日本高知醫(yī)學(xué)院的松崎重信說：“在控制細(xì)菌感染方面,，這些發(fā)現(xiàn)可能相當(dāng)重要,，但要將其應(yīng)用于臨床實(shí)踐,，還需要一段路要走。”研究人員認(rèn)為,，這項(xiàng)研究為找到對付抗生素耐受性細(xì)菌的方法提供了新思路,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS March 2, 2009, doi: 10.1073/pnas.0800442106
Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy
Timothy K. Lua,b and James J. Collinsb,1
aHarvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139; and
bHoward Hughes Medical Institute, Center for BioDynamics and Department of Biomedical Engineering, Boston University, Boston, MA 02215
Antimicrobial drug development is increasingly lagging behind the evolution of antibiotic resistance, and as a result, there is a pressing need for new antibacterial therapies that can be readily designed and implemented. In this work, we engineered bacteriophage to overexpress proteins and attack gene networks that are not directly targeted by antibiotics. We show that suppressing the SOS network in Escherichia coli with engineered bacteriophage enhances killing by quinolones by several orders of magnitude in vitro and significantly increases survival of infected mice in vivo. In addition, we demonstrate that engineered bacteriophage can enhance the killing of antibiotic-resistant bacteria, persister cells, and biofilm cells, reduce the number of antibiotic-resistant bacteria that arise from an antibiotic-treated population, and act as a strong adjuvant for other bactericidal antibiotics (e.g., aminoglycosides and β-lactams). Furthermore, we show that engineering bacteriophage to target non-SOS gene networks and to overexpress multiple factors also can produce effective antibiotic adjuvants. This work establishes a synthetic biology platform for the rapid translation and integration of identified targets into effective antibiotic adjuvants.
