Piatek Magdalena, O'Beirne Cillian, Beato Zoe, Tacke Matthias, Kavanagh Kevin
SSPC Pharma Research Centre, Department of Biology, Maynooth University, W23 F2K8 Maynooth, Co. Kildare, Ireland.
School of Chemistry, University College Dublin, D04 V1W8 Belfield, Dublin 4, Ireland.
Antibiotics (Basel). 2023 Feb 8;12(2):348. doi: 10.3390/antibiotics12020348.
The urgent need to combat antibiotic resistance and develop novel antimicrobial therapies has triggered studies on novel metal-based formulations. -heterocyclic carbene (NHC) complexes coordinate transition metals to generate a broad range of anticancer and/or antimicrobial agents, with ongoing efforts being made to enhance the lipophilicity and drug stability. The lead silver(I) acetate complex, 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) (SBC3), has previously demonstrated promising growth and biofilm-inhibiting properties. In this work, the responses of two structurally different bacteria to SBC3 using label-free quantitative proteomics were characterised. Multidrug-resistant (Gram-negative) and (Gram-positive) are associated with cystic fibrosis lung colonisation and chronic wound infections, respectively. SBC3 increased the abundance of alginate biosynthesis, the secretion system and drug detoxification proteins in , whilst a variety of pathways, including anaerobic respiration, twitching motility and ABC transport, were decreased in abundance. This contrasted the affected pathways in , where increased DNA replication/repair and cell redox homeostasis and decreased protein synthesis, lipoylation and glucose metabolism were observed. Increased abundance of cell wall/membrane proteins was indicative of the structural damage induced by SBC3 in both bacteria. These findings show the potential broad applications of SBC3 in treating Gram-positive and Gram-negative bacteria.
对抗生素耐药性并开发新型抗菌疗法的迫切需求引发了对新型金属基制剂的研究。N-杂环卡宾（NHC）配合物与过渡金属配位，生成多种抗癌和/或抗菌剂，目前正在努力提高其亲脂性和药物稳定性。先导醋酸银（I）配合物1,3-二苄基-4,5-二苯基咪唑-2-亚基（NHC*）（SBC3）此前已显示出有前景的生长抑制和生物膜抑制特性。在这项工作中，使用无标记定量蛋白质组学对两种结构不同的细菌对SBC3的反应进行了表征。多药耐药的铜绿假单胞菌（革兰氏阴性菌）和金黄色葡萄球菌（革兰氏阳性菌）分别与囊性纤维化肺部定植和慢性伤口感染有关。SBC3增加了铜绿假单胞菌中藻酸盐生物合成、分泌系统和药物解毒蛋白的丰度，而包括无氧呼吸、抽动运动和ABC转运在内的多种途径的丰度则降低。这与金黄色葡萄球菌中受影响的途径形成对比，在金黄色葡萄球菌中观察到DNA复制/修复和细胞氧化还原稳态增加，而蛋白质合成、硫辛酸化和葡萄糖代谢减少。细胞壁/膜蛋白丰度的增加表明SBC3在两种细菌中均诱导了结构损伤。这些发现表明SBC3在治疗革兰氏阳性菌和革兰氏阴性菌方面具有潜在的广泛应用。
