Adaptation and preadaptation of Salmonella enterica to Bile.
Adaptation and preadaptation of Salmonella enterica to Bile.
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DOI：
10.1371/journal.pgen.1002459
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发表时间：
2012-01
期刊：
影响因子：
4.5
通讯作者：
Casadesús J
中科院分区：
文献类型：
--
作者：
Hernández SB;Cota I;Ducret A;Aussel L;Casadesús J
胆汁具有抗菌活性，因为胆汁盐破坏细胞膜，使蛋白质变性，并损伤DNA。这项研究描述了肠道沙门氏菌在胆汁中生存的机制。亚致死浓度的胆汁盐脱氧胆酸钠（DOC）使沙门氏菌适应致死浓度的胆汁。适应似乎与基因表达的多种变化有关，其中包括Rpos依赖的一般应激反应和其他应激反应的上调。RpoS−突变体对胆汁敏感的观察结果支持了一般应激反应在适应胆汁中的关键作用。虽然对胆汁的适应涉及细菌群体的反应，但单个细胞可以在没有适应的情况下变得对胆汁具有抗性：在含有致死浓度胆汁的培养基上进行肠杆菌培养，产生的胆汁抗性菌落的频率为每代10−6至10−7个细胞。波动分析表明，这些集落来自先前培养物中存在的胆汁抗性细胞。这些分离株的一部分是稳定的，表明胆汁抗性可以通过突变获得。胆汁抗性突变体的全基因组测序表明，脂多糖转运机制的改变是突变胆汁抗性的常见原因。然而，对致死浓度胆汁的选择也提供了不是突变体的胆汁抗性分离株。我们认为，这些分离物来自罕见的细胞，其生理状态允许生存后，遇到胆汁。这一观点得到了使用显微镜流体系统对基因表达进行单细胞分析的支持：沙门氏菌的分批培养物含有在没有DOC的情况下激活应激反应基因的细胞。这种现象强调了细菌克隆群体中表型异质性的存在，并可能说明基因表达波动的适应价值。本研究描述了肠道沙门氏菌在胆汁中生存的机制：适应、突变和非突变的预适应。在实验室中很容易观察到适应：当沙门氏菌培养物在亚致死浓度的胆盐脱氧胆酸钠（DOC）存在下生长时，DOC的最小抑制浓度增加。适应似乎与DOC诱导的基因表达的多种变化有关。突变性胆汁抗性也是一种常见现象：在含有致死浓度胆汁的琼脂上平板培养可产生胆汁抗性菌落。波动分析表明，这些集落来自先前培养物中存在的胆汁抗性细胞。然而，对致死浓度胆汁的选择也提供了不是突变体的胆汁抗性分离株。非突变的预适应，一个非典型的现象先验，表明批量培养含有罕见的沙门氏菌细胞，其生理状态允许生存后遇到胆汁。非突变性预适应可能是表型异质性的结果，这一观点得到了沙门氏菌培养物中含有在缺乏DOC的情况下激活应激反应基因的细胞的观察结果的支持。
Bile possesses antibacterial activity because bile salts disrupt membranes, denature proteins, and damage DNA. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS− mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colonies at frequencies between 10−6 and 10−7 per cell and generation. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. A fraction of such isolates are stable, indicating that bile resistance can be acquired by mutation. Full genome sequencing of bile-resistant mutants shows that alteration of the lipopolysaccharide transport machinery is a frequent cause of mutational bile resistance. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. We propose that such isolates derive from rare cells whose physiological state permitted survival upon encountering bile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile: adaptation, mutation, and non-mutational preadaptation. Adaptation is easily observed in the laboratory: when a Salmonella culture is grown in the presence of a sublethal concentration of the bile salt sodium deoxycholate (DOC), the minimal inhibitory concentration of DOC increases. Adaptation appears to be associated to multiple changes in gene expression induced by DOC. Mutational bile resistance is also a common phenomenon: plating on agar containing a lethal concentration of bile yields bile-resistant colonies. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. Non-mutational preadaptation, a non-canonical phenomenon a priori, suggests that batch cultures contain rare Salmonella cells whose physiological state permits survival upon encountering bile. The view that non-mutational preadaptation may be a consequence of phenotypic heterogeneity is supported by the observation that Salmonella cultures contain cells that activate stress response genes in the absence of DOC.
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影响因子：
3.5
作者：
Ellermeier, CD;Janakiraman, A;Slauch, JM
通讯作者：
Slauch, JM
DOI：
10.1038/nrmicro2490
发表时间：
2011-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.2
作者：
Garcia-Quintanilla, Meritxell;Prieto, Ana I.;Casadesus, Josep
通讯作者：
Casadesus, Josep
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
DOI：
10.1073/pnas.1000862107
发表时间：
2010-03-02
影响因子：
11.1
作者：
Crawford, Robert W.;Rosales-Reyes, Roberto;Gunn, John S.
通讯作者：
Gunn, John S.