Evaluation of the kinetics and mechanism of action of anti-integration host factor-mediated disruption of bacterial biofilms.
Evaluation of the kinetics and mechanism of action of anti-integration host factor-mediated disruption of bacterial biofilms.
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DOI：
10.1111/mmi.12735
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发表时间：
2014-09
影响因子：
3.6
通讯作者：
Bakaletz LO
中科院分区：
文献类型：
--
作者：
Brockson ME;Novotny LA;Mokrzan EM;Malhotra S;Jurcisek JA;Akbar R;Devaraj A;Goodman SD;Bakaletz LO
许多人类病原体在生物膜形成过程中产生的胞外聚合物通常含有胞外DNA（eDNA）。生物膜基质内的细菌eDNA链可以出现在格子状网络中，其中DNA结合蛋白的DNA BII家族的成员位于每条交叉链的顶点。迄今为止，用针对一种DNABII蛋白质整合宿主因子（IHF）的抗体处理测试的所有生物膜导致显著的破坏。在这里，使用不可分型的流感嗜血杆菌作为模式生物，我们报告说，这种效果是快速的，IHF特异性和介导的结合瞬时解离IHF抗IHF，即使在物理分离的生物膜的核孔膜。此外，生物膜破坏促进了以前无效的抗生素对常驻细菌的杀灭。我们提出的作用机制是隔离IHF从生物膜eDNA解离后，迫使平衡的转变，并最终崩溃的生物膜。此外，针对位于IHF的DNA结合尖端的肽的抗体与针对天然蛋白质的抗体一样有效。由于掺入eDNA和相关DNABII蛋白是由多种人类病原体形成的生物膜的常见策略，因此这种新的治疗方法可能具有广泛的实用性。
The extracellular polymeric substance produced by many human pathogens during biofilm formation often contains extracellular DNA (eDNA). Strands of bacterial eDNA within the biofilm matrix can occur in a lattice-like network wherein a member of the DNABII family of DNA-binding proteins is positioned at the vertex of each crossed strand. To date, treatment of all biofilms tested with antibodies directed against one DNABII protein, Integration Host Factor (IHF), results in significant disruption. Here, using nontypeable Haemophilus influenzae as a model organism, we report that this effect was rapid, IHF-specific and mediated by binding of transiently dissociated IHF by anti-IHF even when physically separated from the biofilm by a nucleopore membrane. Further, biofilm disruption fostered killing of resident bacteria by previously ineffective antibiotics. We propose the mechanism of action to be the sequestration of IHF upon dissociation from the biofilm eDNA, forcing an equilibrium shift and ultimately, collapse of the biofilm. Further, antibodies against a peptide positioned at the DNA-binding tips of IHF were as effective as antibodies directed against the native protein. As incorporating eDNA and associated DNABII proteins is a common strategy for biofilms formed by multiple human pathogens, this novel therapeutic approach is likely to have broad utility.
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影响因子：
3.2
作者：
Jurcisek, Joseph A.;Bakaletz, Lauren O.
通讯作者：
Bakaletz, Lauren O.
影响因子：
2.6
作者：
Brandstetter, Kathleyn A.;Jurcisek, Joseph A.;Das, Subinoy
通讯作者：
Das, Subinoy
影响因子：
4.9
作者：
NICKEL, JC;RUSESKA, I;COSTERTON, JW
通讯作者：
COSTERTON, JW
影响因子：
5.6
作者：
GRANSTON, AE;NASH, HA
通讯作者：
NASH, HA
影响因子：
3.1
作者：
Leroy, Magali;Cabral, Howard;Goldstein, Richard
通讯作者：
Goldstein, Richard