Bouloc P, Vinella D, D'Ari R
Institut Jacques Monod, CNRS, Université Paris, France.
Mol Gen Genet. 1992 Nov;235(2-3):242-6. doi: 10.1007/BF00279366.
We have previously shown that resistance to the beta-lactam mecillinam in Escherichia coli can be brought about by a high ppGpp pool, as observed under conditions of partial amino acid starvation and RelA-dependent induction of the stringent response. We show here that our E. coli wild-type strain, which is sensitive to mecillinam on minimal glucose plates, becomes resistant in the presence of L-leucine or L-serine (or cysteine, which inactivates the antibiotic). The resistance, which is not a transient effect and does not depend on the physiological state of the cells when plated, is specific for mecillinam and is reversed by the presence of isoleucine and valine in the medium. At least in the case of serine, the resistance is RelA-dependent. We conclude that the presence of leucine and serine in the growth medium cause partial starvation for isoleucine/valine, leading to induction of the stringent response and concomitant resistance to mecillinam.
我们之前已经表明，在大肠杆菌中，对β-内酰胺类抗生素美西林的耐药性可由高水平的鸟苷四磷酸（ppGpp）池引起，正如在部分氨基酸饥饿以及RelA依赖的严紧反应诱导条件下所观察到的那样。我们在此表明，我们的大肠杆菌野生型菌株在基本葡萄糖平板上对美西林敏感，但在存在L-亮氨酸或L-丝氨酸（或半胱氨酸，半胱氨酸会使该抗生素失活）时会变得耐药。这种耐药性并非瞬时效应，且不取决于接种时细胞的生理状态，它对美西林具有特异性，并可被培养基中异亮氨酸和缬氨酸的存在所逆转。至少就丝氨酸而言，这种耐药性是RelA依赖的。我们得出结论，生长培养基中亮氨酸和丝氨酸的存在会导致异亮氨酸/缬氨酸的部分饥饿，从而引发严紧反应并伴随对美西林的耐药性。
