Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors.
Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors.
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DOI：
10.2174/1381612043383377
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发表时间：
2004-09
影响因子：
3.1
通讯作者：
K. Tateda;T. Standiford;J. Pechère;K. Yamaguchi
中科院分区：
文献类型：
--
作者：
K. Tateda;T. Standiford;J. Pechère;K. Yamaguchi
铜绿假单胞菌是一种机会致病菌，是囊性纤维化（CF）、弥漫性泛细支气管炎（DPB）和其他形式的支气管扩张患者肺损伤和死亡的主要原因。当一名DPB患者在接受红霉素治疗多年后显著改善时，DPB及其相关的慢性铜绿假单胞菌肺部感染的治疗取得了突破。现在，长期大环内酯类药物治疗已成为DPB患者的一线治疗方法，其免疫调节特性现已扩展到其他临床环境，包括CF。慢性铜绿假单胞菌感染发病机制的一个重要因素是细菌细胞间信号机制，称为“群体感应”，它使细菌能够通过产生自身诱导剂分子来协调打开和关闭特定的毒力基因。干扰或阻断群体感应系统被认为是一种有吸引力的治疗策略。临床和基础科学数据表明，大环内酯类药物可能是假单胞菌群体感应系统的相关抑制剂。事实上，除了抑制多种毒力因子外，某些大环内酯还能强烈抑制群体感应相关基因和自诱导剂的产生。本文就大环内酯类药物治疗DPB和CF的临床疗效作一综述。此外，大环内酯类药物的作用机制将从亚mic大环内酯类药物对铜绿假单胞菌的作用角度进行讨论，特别是这种抗生素抑制群体感应系统的能力，这可能是慢性铜绿假单胞菌感染发病机制的关键。
Pseudomonas aeruginosa is an opportunistic pathogen, and this organism is a major cause of pulmonary damage and mortality in patients with cystic fibrosis (CF), diffuse panbronchiolitis (DPB) and other forms of bronchiectasis. A break-through in the treatment of DPB and associated chronic P. aeruginosa pulmonary infection was realized when a patient with DPB improved dramatically after treatment with erythromycin for years. Now, long-term macrolide therapy has become a first line of treatment in DPB patients, and the immunomodulatory properties have now been extended to other clinical settings, including CF. An important factor in the pathogenesis of chronic P. aeruginosa infection is a bacterial cell-to-cell signaling mechanism, referred to as "quorum sensing", which enables bacteria to coordinately turn on and off specific virulence genes through the production of autoinducer molecules. Interference or blocking of quorum-sensing systems has been considered an attractive therapeutic strategy. Clinical and basic science data suggests the potential of macrolides as relevant inhibitors of the Pseudomonas quorum-sensing system. In fact, certain macrolides strongly suppressed quorum-sensing associated genes and autoinducer production, in addition to inhibition of a variety of virulence factors. In this review, clinical efficacy of macrolides on DPB and CF patients will be briefly summarized. Additionally, the mechanisms of action of macrolides will be discussed from the standpoint of sub-MIC macrolide effects on P. aeruginosa, particularly the ability of this antibiotic to suppress quorum-sensing systems, which may be crucial in the pathogenesis of chronic P. aeruginosa infection.