| Autor: |
Piatek M; SSPC Pharma Research Centre, Department of Biology, Maynooth University, W23 F2K8 Maynooth, Co. Kildare, Ireland., O'Beirne C; School of Chemistry, University College Dublin, D04 V1W8 Belfield, Dublin 4, Ireland., Beato Z; School of Chemistry, University College Dublin, D04 V1W8 Belfield, Dublin 4, Ireland., Tacke M; School of Chemistry, University College Dublin, D04 V1W8 Belfield, Dublin 4, Ireland., Kavanagh K; SSPC Pharma Research Centre, Department of Biology, Maynooth University, W23 F2K8 Maynooth, Co. Kildare, Ireland. |
| Abstrakt: |
The urgent need to combat antibiotic resistance and develop novel antimicrobial therapies has triggered studies on novel metal-based formulations. N -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 Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (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 P. aeruginosa , whilst a variety of pathways, including anaerobic respiration, twitching motility and ABC transport, were decreased in abundance. This contrasted the affected pathways in S. aureus , 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. |
