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细菌生物膜的抗生素耐药性。

Antibiotic resistance of bacterial biofilms.

机构信息

Department of Clinical Microbiology 9301, Juliane Mariesvej 22, Rigshospitalet, 2100 Copenhagen, Denmark.

出版信息

Int J Antimicrob Agents. 2010 Apr;35(4):322-32. doi: 10.1016/j.ijantimicag.2009.12.011. Epub 2010 Feb 10.

DOI:10.1016/j.ijantimicag.2009.12.011
PMID:20149602
Abstract

A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis and other components of the body's defence system. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains. Characteristically, gradients of nutrients and oxygen exist from the top to the bottom of biofilms and these gradients are associated with decreased bacterial metabolic activity and increased doubling times of the bacterial cells; it is these more or less dormant cells that are responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms. Conventional resistance mechanisms such as chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic target molecules in bacteria also contribute to the survival of biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy. A promising strategy may be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and alginate lyase) as well as quorum-sensing inhibitors that increase biofilm susceptibility to antibiotics.

摘要

生物膜是由细菌组成的结构体,嵌入在由多糖、蛋白质和 DNA 组成的自身产生的聚合物基质中。细菌生物膜会导致慢性感染,因为它们对抗生素和消毒剂等化学物质的耐受性增加,并且能够抵抗吞噬作用和身体防御系统的其他成分。例如,与异物相关的葡萄球菌感染的持续存在是由于生物膜的形成。同样,囊性纤维化患者肺部的慢性铜绿假单胞菌感染是由生物膜生长的粘液型菌株引起的。生物膜的特征是从顶部到底部存在营养物质和氧气的梯度,这些梯度与细菌代谢活性降低和细菌细胞倍增时间增加有关;正是这些或多或少处于休眠状态的细胞导致了对某些抗生素的耐受性。生物膜的生长与突变水平的增加以及群体感应调节机制有关。常规的耐药机制,如染色体β-内酰胺酶、上调的外排泵以及细菌中抗生素靶分子的突变,也有助于生物膜的存活。生物膜可以通过早期积极的抗生素预防或治疗来预防,也可以通过慢性抑制治疗来治疗。一种有前途的策略可能是使用能够溶解生物膜基质的酶(例如 DNA 酶和藻酸盐裂解酶)以及增加生物膜对抗生素敏感性的群体感应抑制剂。

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