Mannose Conjugated Polymer Targeting P. aeruginosa Biofilms.
Mannose Conjugated Polymer Targeting P. aeruginosa Biofilms.
复制标题
DOI：
10.1021/acsinfecdis.0c00407
复制
发表时间：
2020-11-13
影响因子：
5.3
通讯作者：
Ratner DM
中科院分区：
文献类型：
--
作者：
Limqueco E;Passos Da Silva D;Reichhardt C;Su FY;Das D;Chen J;Srinivasan S;Convertine A;Skerrett SJ;Parsek MR;Stayton PS;Ratner DM
生物膜是细菌感染中最具挑战性的障碍之一。通过提供针对免疫应答和抗生素治疗的保护，生物膜能够实现慢性定殖和抗生素抗性的发展。如先前的临床观察和研究所示，由于生物膜赋予的保护，单独的传统抗生素疗法不能有效地治疗和消除生物膜形成感染。必须开发一种专门针对生物膜的新策略。在这里，我们专门针对和结合PAO1生物膜，并阐明背后的分子机制之间的相互作用的聚糖靶向聚合物和生物膜使用连续流动生物膜模型。与荧光聚糖靶向聚合物的生物膜的孵育证明了与含甘露糖的聚合物的强烈和持久的相互作用，即使在连续流动24小时后。为了评估主要生物膜蛋白LecB和CdrA的作用，用敲除变体进行的功能丧失实验建立了两种蛋白质在甘露糖靶向聚合物保留中的双重参与。这些结果确定了一个持久的和特定的靶向策略的生物膜，强调其作为一个交付策略的潜在价值，并鼓励进一步探索生物膜靶向交付。
Biofilms are one of the most challenging obstacles in bacterial infections. By providing protection against immune responses and antibiotic therapies, biofilms enable chronic colonization and the development of antibiotic resistance. As previous clinical observations and studies have shown, traditional antibiotic therapy alone cannot effectively treat and eliminate biofilm forming infections due to the protection conferred by the biofilm. A new strategy specifically targeting biofilms must be developed. Here, we specifically target and bind to the PAO1 biofilm and elucidate the molecular mechanism behind the interaction between a glycan targeted polymer and biofilm using a continuous flow biofilm model. The incubation of biofilms with fluorescent glycan targeted polymers demonstrated strong and persistent interactions with the mannose-containing polymer even after 24 h of continuous flow. To evaluate the role of major biofilm proteins LecB and CdrA, loss of function experiments with knockout variants established the dual involvement of both proteins in mannose targeted polymer retention. These results identify a persistent and specific targeting strategy to the biofilm, emphasizing its potential value as a delivery strategy and encouraging further exploration of biofilm targeted delivery.
登录
查看更多内容
影响因子：
6.4
作者：
Reichhardt C;Wong C;Passos da Silva D;Wozniak DJ;Parsek MR
通讯作者：
Parsek MR
影响因子：
11.8
作者：
Kalil, Andre C.;Metersky, Mark L.;Brozek, Jan L.
通讯作者：
Brozek, Jan L.
影响因子：
4.4
作者：
Sønderholm M;Kragh KN;Koren K;Jakobsen TH;Darch SE;Alhede M;Jensen PØ;Whiteley M;Kühl M;Bjarnsholt T
通讯作者：
Bjarnsholt T
影响因子：
16.6
作者：
da Silva, Daniel Passos;Matwichuk, Michael L.;Parsek, Matthew R.
通讯作者：
Parsek, Matthew R.
影响因子：
14
作者：
Chen, Jasmin;Su, Fang-Yi;Ratner, Daniel M.
通讯作者：
Ratner, Daniel M.