Extracellular DNA Shields against Aminoglycosides in Pseudomonas aeruginosa Biofilms
Extracellular DNA Shields against Aminoglycosides in Pseudomonas aeruginosa Biofilms
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DOI：
10.1128/aac.00001-13
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发表时间：
2013-05-01
影响因子：
4.9
通讯作者：
Tolker-Nielsen, Tim
中科院分区：
文献类型：
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作者：
Chiang, Wen-Chi;Nilsson, Martin;Tolker-Nielsen, Tim
近年来，已经确定细胞外DNA是微生物生物膜基质的关键组成部分。此外，最近已经证明DNA结合带正电荷的抗微生物剂，如氨基糖苷类和抗微生物肽。在本研究中，我们提供的证据表明，铜绿假单胞菌生物膜的细胞外DNA屏蔽氨基糖苷类。我们表明，外源补充的DNA整合到铜绿假单胞菌生物膜，并增加他们对氨基糖苷类的耐受性。我们提供的证据表明，由DNA释放缺陷的铜绿假单胞菌群体感应突变体形成的生物膜比野生型生物膜更容易受到氨基糖苷类药物治疗的影响，但在补充外源DNA后，从氨基糖苷类药物的有害作用中获救。此外，我们证明，暴露于裂解的多形核白细胞，这被认为是在感染部位的细胞外DNA的来源，增加铜绿假单胞菌生物膜对氨基糖苷类的耐受性。虽然生物膜相关的氨基糖苷类药物耐受性最近已被链接到细胞外DNA介导的pmr基因的激活，我们证明，由细胞外DNA的存在介导的氨基糖苷类药物耐受性不是由我们的铜绿假单胞菌生物膜中的pmr基因的激活引起的，而是由细胞外DNA的保护性屏蔽效应引起的。
Within recent years, it has been established that extracellular DNA is a key constituent of the matrix of microbial biofilms. In addition, it has recently been demonstrated that DNA binds positively charged antimicrobials such as aminoglycosides and antimicrobial peptides. In the present study, we provide evidence that extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. We show that exogenously supplemented DNA integrates into P. aeruginosa biofilms and increases their tolerance toward aminoglycosides. We provide evidence that biofilms formed by a DNA release-deficient P. aeruginosa quorum-sensing mutant are more susceptible to aminoglycoside treatment than wild-type biofilms but become rescued from the detrimental action of aminoglycosides upon supplementation with exogenous DNA. Furthermore, we demonstrate that exposure to lysed polymorphonuclear leukocytes, which are thought to be a source of extracellular DNA at sites of infections, increases the tolerance of P. aeruginosa biofilms toward aminoglycosides. Although biofilm-associated aminoglycoside tolerance recently has been linked to extracellular DNA-mediated activation of the pmr genes, we demonstrate that the aminoglycoside tolerance mediated by the presence of extracellular DNA is not caused by activation of the pmr genes in our P. aeruginosa biofilms but rather by a protective shield effect of the extracellular DNA.