Transient Antibiotic Tolerance Triggered by Nutrient Shifts From Gluconeogenic Carbon Sources to Fatty Acid.
Transient Antibiotic Tolerance Triggered by Nutrient Shifts From Gluconeogenic Carbon Sources to Fatty Acid.
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DOI：
10.3389/fmicb.2022.854272
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发表时间：
2022
影响因子：
5.2
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Hartline CJ;Zhang R;Zhang F
营养物质从糖酵解碳源向糖异生碳源的转变可以产生大量对抗生素极其耐受的细菌亚群，称为持久菌。大肠杆菌中央代谢的正反馈被认为在持久细胞的形成中发挥关键作用。为了检查营养物运输中的正反馈是否也可以支持β-内酰胺的高持久性，我们对大肠杆菌进行了从糖异生碳源到脂肪酸（FA）的营养物转变。我们观察到三相抗生素杀死动力学，其特征是短暂的高抗生素耐受期，随后是快速杀死，然后是较慢的持久性杀死阶段。短暂耐受的持续时间（3-44小时）随转变前碳源的不同而变化，并与转变后积累FA降解酶FadD所需的时间密切相关。此外，通过在切换之前引入乙醛酸旁路，可以减少 FadD 累积时间和瞬态耐受时间，这凸显了两个相互作用的反馈环路同时控制瞬态耐受的长度。我们的结果表明，营养转换和正反馈不足以引发大多数人群的持久性，而只能引发暂时的耐受性。此外，我们的结果表明，转变前的代谢状态决定了短暂耐受的持续时间，并且提供乙醛酸盐可以促进抗生素杀死细菌。
Nutrient shifts from glycolytic-to-gluconeogenic carbon sources can create large sub-populations of extremely antibiotic tolerant bacteria, called persisters. Positive feedback in Escherichia coli central metabolism was believed to play a key role in the formation of persister cells. To examine whether positive feedback in nutrient transport can also support high persistence to β-lactams, we performed nutrient shifts for E. coli from gluconeogenic carbon sources to fatty acid (FA). We observed tri-phasic antibiotic killing kinetics characterized by a transient period of high antibiotic tolerance, followed by rapid killing then a slower persister-killing phase. The duration of transient tolerance (3–44 h) varies with pre-shift carbon source and correlates strongly with the time needed to accumulate the FA degradation enzyme FadD after the shift. Additionally, FadD accumulation time and thus transient tolerance time can be reduced by induction of the glyoxylate bypass prior to switching, highlighting that two interacting feedback loops simultaneously control the length of transient tolerance. Our results demonstrate that nutrient switches along with positive feedback are not sufficient to trigger persistence in a majority of the population but instead triggers only a temporary tolerance. Additionally, our results demonstrate that the pre-shift metabolic state determines the duration of transient tolerance and that supplying glyoxylate can facilitate antibiotic killing of bacteria.
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影响因子：
4.5
作者：
Bernier SP;Lebeaux D;DeFrancesco AS;Valomon A;Soubigou G;Coppée JY;Ghigo JM;Beloin C
通讯作者：
Beloin C
影响因子：
16
作者：
Amato, Stephanie M.;Orman, Mehmet A.;Brynildsen, Mark P.
通讯作者：
Brynildsen, Mark P.
影响因子：
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作者：
Clark, David P;Cronan, John E
通讯作者：
Cronan, John E
影响因子：
3.9
作者：
Aslam B;Wang W;Arshad MI;Khurshid M;Muzammil S;Rasool MH;Nisar MA;Alvi RF;Aslam MA;Qamar MU;Salamat MKF;Baloch Z
通讯作者：
Baloch Z
DOI：
10.1073/pnas.0711712105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Gefen, Orit;Gabay, Chana;Balaban, Nathalie Q.
通讯作者：
Balaban, Nathalie Q.