Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria
Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria
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DOI：
10.1016/s0092-8674(00)81928-5
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发表时间：
1997-03-21
期刊：
影响因子：
64.5
通讯作者：
Normark, S
中科院分区：
文献类型：
--
作者：
Jacobs, C;Frere, JM;Normark, S
革兰氏阴性菌中染色体β-内酰胺酶的β-内酰胺诱导需要转录调节因子AmpR和胞壁素分解产物（胞壁肽）转运到细胞质中。体外转录表明，纯化的AmpR作为ampC β-内酰胺酶合成的激活剂。胞壁素前体UDP-MurNAc-五肽降低体外AmpR介导的转录激活，但对体内介导ampC组成性激活的AmpR（G102 E）突变体没有影响。添加在β-内酰胺酶过量产生突变体中积累的胞肽，anhMurNAc-三肽，抵消了UDP-MurNAc-五肽的负面作用，恢复了AmpR在体外诱导ampC表达的先天能力。胞质中间体的murein生物合成和降解，从而拮抗作用，以控制β-内酰胺酶的表达，从而作为一个细胞壁的传感装置。
beta-lactam induction of chromosomal beta-lactamase in gram-negative bacteria requires the transcriptional regulator AmpR and the transport of murein breakdown products (muropeptides) into the cytoplasm. In vitro transcription shows that purified AmpR acts as an activator for ampC beta-lactamase synthesis. The murein precursor, UDP-MurNAc-pentapeptide, decreases AmpR-mediated transcriptional activation in vitro, but has no effect on an AmpR(G102E) mutant that mediates constitutive activation of ampC in vivo. Addition of the muropeptide, anhMurNAc-tripeptide, which accumulates in beta-lactamase-overproducing mutants, counteracts the negative effect of UDP-MurNAc-pentapeptide, restoring the innate ability of AmpR to induce ampC expression in vitro. Cytosolic intermediates of murein biosynthesis and degradation thus act antagonistically to control beta-lactamase expression, thereby operating as a cell-wall sensing device.