EPISTATIC EFFECTS OF PROMOTER AND REPRESSOR FUNCTIONS OF THE TN10 TETRACYCLINE-RESISTANCE OPERON ON THE FITNESS OF ESCHERICHIA-COLI
EPISTATIC EFFECTS OF PROMOTER AND REPRESSOR FUNCTIONS OF THE TN10 TETRACYCLINE-RESISTANCE OPERON ON THE FITNESS OF ESCHERICHIA-COLI
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DOI：
10.1111/j.1365-294x.1994.tb00113.x
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发表时间：
1994-04-01
影响因子：
4.9
通讯作者：
BERTRAND, KP
中科院分区：
文献类型：
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作者：
LENSKI, RE;SOUZA, V;BERTRAND, KP
我们一直在研究质粒传播、Tn10 编码的四环素抗性表达对大肠杆菌 K12 适应性的影响。我们之前证明了抗性蛋白的诱导或组成型表达会导致适应性的大幅降低；然而，受抑制操纵子的任何残留表达都很轻微，因此在没有抗生素的情况下，具有诱导性抗性功能基本上不会造成任何负担。在这里，我们证明了诱导基因型相对于等基因组成型构建体的两个明显缺点。在从不含抗生素的培养基向含抗生素培养基的转变过程中，诱导型基因型在生长前经历了较长的滞后期。在抗生素持续存在的情况下，可诱导基因型中抗性功能的完全诱导被其阻遏物的持续作用所阻止。然而，可以通过增加诱导型基因型中抗性基因的启动子强度来减少这些缺点。同时考虑基因调控模式（即组成型或诱导型）和抗性基因启动子的强度（即最大表达水平）表明具有非常强的上位性和多个适应峰的适应性景观。
We have been studying the effects of expression of plasmid-borne, Tn10-encoded, tetracycline resistance on the fitness of Escherichia coli K12. We previously demonstrated large reductions in fitness resulting from induced or constitutive expression of the resistance protein; however, any residual expression by the repressed operon was so slight that possession of an inducible resistance function imposed essentially no burden in the absence of antibiotic. Here, we demonstrate two distinct disadvantages for inducible genotypes relative to isogenic constitutive constructs. During the transition from antibiotic-free to antibiotic-containing media, the inducible genotype experiences a longer lag phase prior to growth. In the sustained presence of antibiotic, full induction of the resistance function in the inducible genotype is prevented by the continued action of its repressor. However, these disadvantages may be reduced by increasing the strength of the promoter for the resistance gene in the inducible genotype. Simultaneous consideration of the mode of gene regulation (i.e. constitutive or inducible) and the strength of the resistance-gene promoter (i.e. maximum level of expression) indicates an adaptive landscape with very strong epistasis and, perhaps, multiple fitness peaks.