Optimization of Phage-Antibiotic Combinations against Staphylococcus aureus Biofilms.
Optimization of Phage-Antibiotic Combinations against Staphylococcus aureus Biofilms.
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针对金黄色葡萄球菌生物膜的噬菌体-抗生素组合的优化。
DOI：
10.1128/spectrum.04918-22
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发表时间：
2023-06-15
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
由于耐药细菌的传播和新型抗生素的狭窄管道，噬菌体治疗引起了人们的关注。假设噬菌体鸡尾酒通过用一种以上的噬菌体挑战细菌来减缓抗性的总体发展。在这里，我们已经使用了基于平板、渗透压和生物膜的筛选试验的组合，以尝试鉴定噬菌体-抗生素组合，其将根除金黄色葡萄球菌菌株的预先形成的生物膜，否则难以杀死。我们专注于耐甲氧西林金黄色葡萄球菌（MRSA）菌株及其达托霉素不敏感的万古霉素中间体（DNS-VISA）衍生物，以了解噬菌体-抗生素相互作用是否因从MRSA演变为DNS-VISA（已知发生在接受抗生素治疗的患者中）相关的变化而改变。我们评估了五个专性溶菌性链球菌的寄主范围和交叉抗性模式。金黄色葡萄球菌噬菌体以选择三噬菌体混合物。我们筛选了这些细菌对24小时珠生物膜的活性，发现两种菌株D 712（DNS-VISA）和8014（MRSA）的生物膜对单一细菌的杀灭最具抗性。具体地，即使每孔IO 7 PFU的初始噬菌体浓度也不能防止细菌从经处理的生物膜的可见再生长。然而，当我们用噬菌体-抗生素组合处理相同两种菌株的生物膜时，当使用低于我们测量的最小生物膜抑制浓度的高达4个数量级的噬菌体和抗生素浓度时，我们阻止了细菌再生长。我们没有看到噬菌体活性和DNS-VISA基因型在这少量细菌菌株中的进化之间的一致关联。重要性生物膜的细胞外聚合物基质阻碍抗生素的扩散，促进多重耐药群体的出现。虽然大多数噬菌体混合物是为细菌的非稳态状态设计的，但重要的是要考虑生物膜生长模式（自然界中细菌生长的主要模式），因为尚不清楚任何特定噬菌体及其细菌宿主之间的相互作用如何取决于生长环境的物理性质。此外，细菌对任何给定噬菌体的敏感性程度可以从嗜热状态到生物膜状态变化。因此，靶向生物膜感染（例如导管和假体关节材料）的含噬菌体治疗可能不仅仅基于宿主范围特征。我们的研究结果开辟了新的问题，关于噬菌体抗生素治疗效率的拓扑结构的生物膜设置的根除和根除效果的程度相对于单一的代理人在生物膜种群。
Phage therapy has gained attention due to the spread of antibiotic-resistant bacteria and narrow pipeline of novel antibiotics. Phage cocktails are hypothesized to slow the overall development of resistance by challenging the bacteria with more than one phage. Here, we have used a combination of plate-, planktonic-, and biofilm-based screening assays to try to identify phage-antibiotic combinations that will eradicate preformed biofilms of Staphylococcus aureus strains that are otherwise difficult to kill. We have focused on methicillin-resistant S aureus (MRSA) strains and their daptomycin-nonsusceptible vancomycin-intermediate (DNS-VISA) derivatives to understand whether the phage-antibiotic interactions are altered by the changes associated with evolution from MRSA to DNS-VISA (which is known to occur in patients receiving antibiotic therapy). We evaluated the host range and cross-resistance patterns of five obligately lytic S. aureus myophages to select a three-phage cocktail. We screened these phages for their activity against 24-h bead biofilms and found that biofilms of two strains, D712 (DNS-VISA) and 8014 (MRSA), were the most resistant to killing by single phages. Specifically, even initial phage concentrations of 107 PFU per well could not prevent visible regrowth of bacteria from the treated biofilms. However, when we treated biofilms of the same two strains with phage-antibiotic combinations, we prevented bacterial regrowth when using up to 4 orders of magnitude less phage and antibiotic concentrations that were lower than our measured minimum biofilm inhibitory concentration. We did not see a consistent association between phage activity and the evolution of DNS-VISA genotypes in this small number of bacterial strains. IMPORTANCE The extracellular polymeric matrix of biofilms presents an impediment to antibiotic diffusion, facilitating the emergence of multidrug-resistant populations. While most phage cocktails are designed for the planktonic state of bacteria, it is important to take the biofilm mode of growth (the predominant mode of bacterial growth in nature) into consideration, as it is unclear how interactions between any specific phage and its bacterial hosts will depend on the physical properties of the growth environment. In addition, the extent of bacterial sensitivity to any given phage may vary from the planktonic to the biofilm state. Therefore, phage-containing treatments targeting biofilm infections such as catheters and prosthetic joint material may not be merely based on host range characteristics. Our results open avenues to new questions regarding phage-antibiotic treatment efficiency in the eradication of topologically structured biofilm settings and the extent of eradication efficacy relative to the single agents in biofilm populations.
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影响因子：
2.4
作者：
Kelly, D.;McAuliffe, O.;Coffey, A.
通讯作者：
Coffey, A.
影响因子：
9.4
作者：
Ceri, H;Olson, ME;Buret, A
通讯作者：
Buret, A
影响因子：
4.9
作者：
Kebriaei, Razieh;Lev, Katherine L.;Rybak, Michael J.
通讯作者：
Rybak, Michael J.
DOI：
10.1007/978-1-4939-0473-0_48
发表时间：
2014-01-01
期刊：
PSEUDOMONAS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Coffey, Barbara M.;Anderson, Gregory G.
通讯作者：
Anderson, Gregory G.
影响因子：
4.8
作者：
Abedon, Stephen T.
通讯作者：
Abedon, Stephen T.