通过更好地了解铜绿假单胞菌生物膜的形成和生物膜介导的耐药性,获得更好的治疗方案

Biofilms Pub Date : 2020-07-01 DOI:10.5194/biofilms9-138
Jules D. P. Valentin, A. Varadarajan, C. Ahrens, H. C. Mei, Q. Ren
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引用次数: 1

摘要

与浮游细菌相比,生活在生物膜中的细菌可耐受更高浓度的抗生素,并可引起慢性感染。在最难治疗的病原体中,铜绿假单胞菌是许多生物膜相关感染和囊性纤维化气道感染相关死亡率的主要原因。我们推测生物膜中有特定的基因负责增加抗生素耐药性,目的是在铜绿假单胞菌中鉴定它们。通过这样做,可以更好地了解生物膜介导的耐药性,并可以确定新的细菌靶点。筛选铜绿假单胞菌转座子突变体文库,评估其对生物膜形成及生物膜耐药性的影响。简而言之,通过跟踪暴露于不同浓度抗生素的生物膜细胞的再生长来估计生物膜耐药性。一些候选物质,如参与营养摄取的反应调节因子CbrB,已被确定为生物膜形成和抗生素耐药性的关键。对这些有趣的基因进行了进一步的表征,以探索抗性的潜在机制。这些知识可以导致铜绿假单胞菌生物膜的敏感性鉴定,并有助于开发治疗持续感染的工具。
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Better treatment options through a better understanding of Pseudomonas aeruginosa biofilm formation and biofilm-mediated resistance

Bacteria living in biofilms tolerate much higher antibiotic concentrations compared to planktonic bacteria and can cause chronic infections. Among the most difficult pathogens to treat, Pseudomonas aeruginosa is responsible for many biofilm-related infections and for much of the mortality associated with airway infections in cystic fibrosis. We speculated that there are specific genes responsible for increased antibiotic resistance in biofilms and aimed to identify them in P. aeruginosa. By doing so, a better understanding of biofilm-mediated resistance can be achieved and new bacterial targets can be identified. A P. aeruginosa transposon mutant library was screened to assess the impact on biofilm formation and the biofilm resistance toward antibiotics. Briefly, the biofilm resistance was estimated by following the re-growth of biofilm cells exposed to different concentrations of antibiotics. A few candidates, e. g. the response regulator CbrB, involved in nutrient uptake, have been identified as crucial for biofilm formation and resistance towards antibiotics. Further characterization of these interesting genes has been carried out to explore the underlying mechanism of resistance. Such knowledge can lead to the identification of susceptibility of P. aeruginosa biofilm and help to develop tools to treat persistent infections.

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