A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance
A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance
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DOI：
10.1038/nature02122
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发表时间：
2003-11-20
期刊：
影响因子：
64.8
通讯作者：
O'Toole, GA
中科院分区：
文献类型：
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作者：
Mah, TF;Pitts, B;O'Toole, GA
生物膜是表面附着的微生物群落，具有与其自由游动的浮游生物不同的特征性结构、表型和生化特性（1）。这些生物膜特异性特性中最著名的一个是抗生素耐药性的发展，其可高达1,000倍于嗜酸性细胞（2）。我们报告了革兰氏阴性机会致病菌铜绿假单胞菌这种高水平耐药的遗传决定因素。我们已经鉴定了铜绿假单胞菌的突变体，其虽然仍然能够形成具有特征性铜绿假单胞菌结构的生物膜，但不会对三种不同类别的抗生素产生高水平的生物膜特异性抗性。在我们的筛选中鉴定的基因座ndvB是周质葡聚糖合成所需的。我们发现这些周质葡聚糖与妥布霉素发生物理相互作用，这表明这些葡萄糖聚合物可能通过将这些抗菌剂隔离在周质中来阻止抗生素到达其作用部位。我们的研究结果表明，生物膜本身不仅仅是这些抗生素的扩散屏障，而是这些微生物群落中的细菌采用不同的机制来抵抗抗菌剂的作用。
Biofilms are surface-attached microbial communities with characteristic architecture and phenotypic and biochemical properties distinct from their free-swimming, planktonic counterparts(1). One of the best-known of these biofilm-specific properties is the development of antibiotic resistance that can be up to 1,000-fold greater than planktonic cells(2). We report a genetic determinant of this high-level resistance in the Gram-negative opportunistic pathogen, Pseudomonas aeruginosa. We have identified a mutant of P. aeruginosa that, while still capable of forming biofilms with the characteristic P. aeruginosa architecture, does not develop high-level biofilm-specific resistance to three different classes of antibiotics. The locus identified in our screen, ndvB, is required for the synthesis of periplasmic glucans. Our discovery that these periplasmic glucans interact physically with tobramycin suggests that these glucose polymers may prevent antibiotics from reaching their sites of action by sequestering these antimicrobial agents in the periplasm. Our results indicate that biofilms themselves are not simply a diffusion barrier to these antibiotics, but rather that bacteria within these microbial communities employ distinct mechanisms to resist the action of antimicrobial agents.