From Silver(I) Exposure to Bacterial Defense: Focus on Sil and Cus Systems
Silver ions (Ag+) have been shown to possess antimicrobial properties. However, some Gram-negative bacteria have evolved sophisticated mechanisms to tolerate their toxicity. Among these, the plasmid-encoded Sil system and the chromosomal Cus system are key efflux-based resistance mechanisms. The Sil system is composed of a two-component regulator (SilS and SilR), periplasmic chaperones (SilF, SilG, and SilE), a P-type ATPase (SilP), and a tripartite efflux pump (SilABC) to sense, sequester, and export Ag+. SilE, a small periplasmic protein, plays a pivotal role by binding multiple Ag+ through histidine and methionine residues, which undergo a transition from disordered to α-helical conformations upon Ag+ coordination. A comparative analysis with the Cus system reveals that, while CusF and CusABC perform analogous metal-binding and efflux functions, Cus primarily targets Cu+ and lacks auxiliary components such as SilP and SilE. Collectively, these two systems demonstrate the adaptive strategies that bacteria have developed to regulate toxic metal ion concentrations.
DOI: 10.29245/2689-9981/2026/4.1188 View / Download PdfLaboratory Validation of EUCAST Rapid Antimicrobial Susceptibility Testing (RAST) and Its Clinical Impact on Sepsis Management
In sepsis, the most decisive modifiable factor influencing survival is the early administration of appropriate antimicrobial therapy. The turnaround time to obtain the conventional antimicrobial susceptibility testing results is 16–24 hours post-blood culture-positive results, which can delay targeted therapy administration and prolong empirical broad-spectrum antibiotic usage. The rapid antimicrobial susceptibility testing (RAST) method proposed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) enables disk diffusion-based susceptibility interpretation directly from positive blood cultures within 4–8 hours. However, the clinical utility of RAST is dependent on rigorous laboratory validation to ensure acceptable analytical performance and minimize categorical errors. This mini review summarizes recent evidence on the EUCAST RAST methodology, validation requirements, analytical performance metrics, implementation strategies, and clinical impact in bloodstream infections and sepsis. The importance of local validation aligning with EUCAST quality control recommendations and the role of RAST in strengthening antimicrobial stewardship programs and supporting global antimicrobial resistance containment efforts have been discussed.
DOI: 10.29245/2689-9981/2026/4.1187 View / Download Pdf