Shambharkar Akash, Thompson Thomas P, McClenaghan Laura A, Bourke Paula, Gilmore Brendan F, Skvortsov Timofey
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Plasma Research Group, School of Biosystems and Food Engineering, University College Dublin, Dublin 4, Ireland.
Biofilm. 2024 Oct 18;8:100230. doi: 10.1016/j.bioflm.2024.100230. eCollection 2024 Dec.
The ongoing antimicrobial resistance crisis has incentivised research into alternative antibacterial and antibiofilm agents. One of them is plasma-activated water (PAW), which is produced by exposing water to a cold plasma discharge. This process generates a diverse array of reactive oxygen and nitrogen species (ROS/RNS) with antimicrobial properties. Another intensively studied class of alternative antimicrobials are bacteriophages, attracting attention due to their specificity and strong antibacterial activity. As combinations of different types of antimicrobials are known to often exhibit synergistic interactions, in this study we investigated the combined use of cold atmospheric-pressure plasma-activated water and the bacteriophage vB_PmiS_PM-CJR against biofilms as a potential option for treatment of catheter-associated urinary tract infections (CAUTIs). We compared the effect of two cold plasma discharge setups for PAW production on its antimicrobial efficacy against planktonic and biofilm cultures. Next, we assessed the stability of the phage vB_PmiS_PM-CJR in PAW. Finally, we tested the antimicrobial activity of the phages and PAW against biofilms, both individually and in combinations. Our findings demonstrate that the combination of PAW with phage is more effective against biofilms compared to individual treatments, being able to reduce the number of biofilm-embedded cells by approximately 4 log. We were also able to show that the order of treatment plays an important role in the anti-biofilm activity of the phage-PAW combination, as the exposure of the biofilm to PAW prior to phage administration results in a stronger effect than the reverse order. This research underlines PAW's ability to potentiate phage activity, showcasing a considerable reduction in biofilm viability and biomass. Additionally, it contributes to the growing body of evidence supporting the use of phage-based combinatorial treatments. Overall, this sequential treatment strategy demonstrates the potential of leveraging multiple approaches to address the mounting challenge of antibiotic resistance and offers a promising avenue for enhancing the efficacy of CAUTI management.
持续的抗菌药物耐药性危机促使人们对替代抗菌和抗生物膜药物展开研究。其中之一是等离子体活化水（PAW），它是通过将水暴露于冷等离子体放电中产生的。这个过程会产生一系列具有抗菌特性的活性氧和氮物种（ROS/RNS）。另一类经过深入研究的替代抗菌剂是噬菌体，因其特异性和强大的抗菌活性而受到关注。由于已知不同类型抗菌剂的组合通常会表现出协同相互作用，在本研究中，我们调查了冷大气压等离子体活化水与噬菌体vB_PmiS_PM-CJR联合使用对生物膜的作用，作为治疗导管相关性尿路感染（CAUTIs）的一种潜在选择。我们比较了两种用于生产PAW的冷等离子体放电装置对其针对浮游菌和生物膜培养物的抗菌效果。接下来，我们评估了噬菌体vB_PmiS_PM-CJR在PAW中的稳定性。最后，我们测试了噬菌体和PAW单独及联合对生物膜的抗菌活性。我们的研究结果表明，与单独处理相比，PAW与噬菌体的组合对生物膜更有效，能够将生物膜内包埋细胞的数量减少约4个对数级。我们还能够证明处理顺序在噬菌体-PAW组合的抗生物膜活性中起着重要作用，因为在施用噬菌体之前将生物膜暴露于PAW会产生比相反顺序更强的效果。这项研究强调了PAW增强噬菌体活性的能力，显示出生物膜活力和生物量的显著降低。此外，它为支持基于噬菌体的联合治疗的越来越多的证据做出了贡献。总体而言，这种序贯治疗策略展示了利用多种方法应对日益严峻的抗生素耐药性挑战的潜力，并为提高CAUTI管理的疗效提供了一条有前景的途径。
