Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms.
Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms.
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DOI：
10.1016/j.bioflm.2022.100074
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发表时间：
2022-12
期刊：
影响因子：
6.8
通讯作者：
Sandoe JAT
中科院分区：
文献类型：
--
作者：
Caudwell JA;Tinkler JM;Johnson BRG;McDowall KJ;Alsulaimani F;Tiede C;Tomlinson DC;Freear S;Turnbull WB;Evans SD;Sandoe JAT
金黄色葡萄球菌(S.金黄色葡萄球菌）是一种重要的人类病原体和血流感染的常见原因。S.金黄色葡萄球菌形成生物膜，特别是在医疗器械上形成生物膜，使得治疗变得困难，因为其倾向于在体内扩散并引起继发性感染病灶。严重的链球菌通常需要延长静脉抗菌治疗疗程。金黄色葡萄球菌感染。本文研究了微泡对S. AClfA1靶向凝集因子A（ClfA）毒力因子--一种与表面附着相关的细胞壁锚定蛋白。微泡（MB）是由脂质、聚合物或蛋白质单层或其他基于表面活性剂的材料封装的微米尺寸的充气气泡。Affimers是一种小分子（约12 kDa）的热稳定结合蛋白，是抗体的替代品。结果表明，AClfA1与S.金黄色葡萄球菌ClfA具有较强的结合亲和力（KD = 62 ± 3nM）。然后显示AClfA1与S.金黄色葡萄球菌生物膜在流动条件下作为游离配体和当结合到微粒（聚合物珠或微泡）时。用AClfA1功能化的微泡与用相同的Affimer支架但缺少识别基团功能化的微泡相比，结合增加了8倍。结合的MBs能够承受250 μ L/min的流速。最后，应用超声破裂生物膜结合的MBs，以确定这是否会导致生物膜生物量损失或细胞死亡。将2.25MHz的超声分布（具有0.8MPa的峰值负压并且由22个周期的正弦波组成，脉冲重复率为10kHz）施加到用靶向MB修饰的生物膜上持续2s，导致生物量损失增加25%并且死细胞计数伴随增加8%。本研究结果表明，Affimers可以作为靶向S.金黄色葡萄球菌生物膜，并且这样的Affimers可以附着到造影剂例如微泡或聚合物珠上，并且在一些优化的情况下，提供了用于无药物生物膜治疗的潜力。
Staphylococcus aureus (S. aureus) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor – a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (KD = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 μL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment.
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影响因子：
6.7
作者：
Anderson CR;Rychak JJ;Backer M;Backer J;Ley K;Klibanov AL
通讯作者：
Klibanov AL
影响因子：
6.7
作者：
Chavakis, T;Wiechmann, K;Herrmann, M
通讯作者：
Herrmann, M
影响因子：
4.6
作者：
Ingels, Alexandre;Leguerney, Ingrid;Lassau, Nathalie
通讯作者：
Lassau, Nathalie
DOI：
10.1046/j.1540-8175.2002.00229.x
发表时间：
2002-04-01
影响因子：
1.5
作者：
de Jong, N;Bouakaz, A;Frinking, P
通讯作者：
Frinking, P
影响因子：
2.7
作者：
Allison, DG
通讯作者：
Allison, DG