研究人員發(fā)現(xiàn)了當(dāng)受到抗菌素圍攻時(shí)某些細(xì)菌采取的一種新的存活方式,。這種存活機(jī)制與其它已知的細(xì)菌存活策略有著根本的不同,。了解這一點(diǎn)可能對(duì)設(shè)計(jì)以難治菌株為標(biāo)靶的藥物有用，例如耐藥性結(jié)核病——這是一個(gè)正在變得越來(lái)越緊迫的公共衛(wèi)生問(wèn)題。這項(xiàng)研究所基于的是恥垢分枝桿菌，它是一種與TB致病菌有親緣的細(xì)菌。
以往的實(shí)驗(yàn)顯示,，某些細(xì)菌在接觸抗菌素時(shí)能夠存活是因?yàn)樵谄渚褐写嬖谥蝗翰贿M(jìn)行細(xì)胞分裂的“耐藥株細(xì)胞”，它們甚至是在抗菌素治療開始之前就已經(jīng)存在于菌群之中了,。 Wakamoto及其同事現(xiàn)在報(bào)告說(shuō),，不進(jìn)行細(xì)胞分裂的耐藥株細(xì)胞與接觸異煙肼的恥垢分枝桿菌的存活無(wú)關(guān)。實(shí)際上,，細(xì)胞的存活與其生長(zhǎng)率毫無(wú)關(guān)系,。相反，一種叫做KatG的細(xì)菌酶的隨機(jī)脈沖使得某些細(xì)菌細(xì)胞在抗菌素治療中存活下來(lái)成為可能,。
研究人員對(duì)經(jīng)過(guò)異煙肼處理的微流控培養(yǎng)中的單一的恥垢分枝桿菌細(xì)胞進(jìn)行了研究,。該藥是一種“前體藥物”,，它要在給藥后并與細(xì)胞中某些化合物相互作用之后才會(huì)變得有活性。在恥垢分枝桿菌的這種情況下,，是KatG激活了異煙肼,。個(gè)體細(xì)菌細(xì)胞的命運(yùn)不與其生長(zhǎng)速度相關(guān)，但與其KatG的產(chǎn)出相關(guān),。每個(gè)細(xì)菌細(xì)胞以隨機(jī)脈沖方式所產(chǎn)生的KatG決定了該細(xì)菌細(xì)胞存活的機(jī)會(huì),。研究人員得出結(jié)論：在某些細(xì)胞中，在有些脈沖間期中,，前體藥物的酶轉(zhuǎn)化幾乎是不可能的,。因此，有一些細(xì)菌細(xì)胞可能會(huì)避免被激活的抗菌素殺滅,。(生物谷Bioon.com)
DOI: 10.1126/science.1229858
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Dynamic Persistence of Antibiotic-Stressed Mycobacteria
Yuichi Wakamoto1,*,†, Neeraj Dhar1,*, Remy Chait2,‡, Katrin Schneider1, François Signorino-Gelo1,Stanislas Leibler2,3, John D. McKinney1,§
Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing “persisters.” Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.
