革兰氏阴性菌中β-内酰胺酶诱导表达调控机制研究进展

Progress in regulatory mechanism for inducing β-lactamase in Gram-negative bacteria

摘要:

β-内酰胺类抗生素是应用最广的一类抗菌药物。β-内酰胺酶能将β-内酰胺类抗生素水解，其诱导表达是革兰氏阴性菌对该类抗生素产生耐药性的最主要原因。文中重点综述了革兰氏阴性菌中β-内酰胺酶诱导表达的两种调控机制。在经典的ampR-ampC调控系统中，β-内酰胺酶的诱导表达与肽聚糖循环密切相关，并且LysR型转录因子AmpR发挥核心的调控作用。近年来发现β-内酰胺类抗生素能激活双组分系统，从而诱导β-内酰胺酶的表达。最后，讨论了革兰氏阴性菌中β-内酰胺类耐药今后的研究方向。

关键词:革兰氏阴性菌，β-内酰胺类抗生素，β-内酰胺酶，调控机制，双组分系统

Abstract:

Beta-lactams are the most widely used antibiotics. One of the principle mechanisms for Gram-negative bacteria to resist β-lactams is by producing β-lactamases that degrade β-lactams. This review highlights two regulatory mechanisms for inducing β-lactamase in Gram-negative bacteria. In the ampR-ampC paradigm, the induction of β-lactamase is intimately linked to peptidoglycan recycling. AmpR, a LysR-type transcriptional regulator, plays a central role in regulating expression of β-lactamase. Recent studies found that two-component signal transduction pathway is activated by β-lactams, which in turn induces the expression of β-lactamase. Finally, we discussed the future research directions in β-lactam resistance in Gram-negative bacteria.

Key words:Gram-negative bacteria, β-lactam antibiotics, β-lactamase, regulatory mechanism, two-component system