<i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Display Differential Proteomic Responses to the Silver(I) Compound, SBC3

• Main Authors: Magdalena Piatek (Author), Cillian O'Beirne (Author), Zoe Beato (Author), Matthias Tacke (Author), Kevin Kavanagh (Author)
• Format: Book
• Published: MDPI AG, 2023-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics12020348; 2079-6382
• Keywords: antimicrobial; proteome; silver; <i>Pseudomonas</i>; <i>Staphylococcus</i>; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 12, Iss 2, p 348 (2023)

The urgent need to combat antibiotic resistance and develop novel antimicrobial therapies has triggered studies on novel metal-based formulations. <i>N</i>-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 <i>Pseudomonas aeruginosa</i> (Gram-negative) and <i>Staphylococcus aureus</i> (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 <i>P. aeruginosa</i>, whilst a variety of pathways, including anaerobic respiration, twitching motility and ABC transport, were decreased in abundance. This contrasted the affected pathways in <i>S. aureus</i>, 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.