The crystal structure of a previously reported antimicrobial RuII complex that targets bacterial DNA is presented. Studies utilizing clinical isolates of Gram-negative bacteria that cause catheter-associated urinary tract infection, (CA)UTI, in media that model urine and plasma reveal that good antimicrobial activity is maintained in all conditions tested. Experiments with a series of Staphylococcus aureus clinical isolates show that, unlike the majority of previously reported RuII-based antimicrobial leads, the compound retains its potent activity even in MRSA strains. Furthermore, experiments using bacteria in early exponential growth and at different pHs reveal that the compound also retains its activity across a range of conditions that are relevant to those encountered in clinical settings. Combinatorial studies involving cotreatment with conventional antibiotics or a previously reported analogous dinuclear RuII complex showed no antagonistic effects. In fact, although all combinations show distinct additive antibacterial activity, in one case, this effect approaches synergy. It was found that the Galleria Mellonella model organism infected with a multidrug resistant strain of the ESKAPE pathogen Acinetobacter baumannii could be successfully treated and totally cleared within 48 h after a single dose of the lead complex with no detectable deleterious effect to the host.
Copper oxide nanoparticles (CuONPs) offer promising antimicrobial properties against a range of pathogens, addressing the urgent issue of antibiotic resistance. This study details the synthesis of glutamic acid-coated CuONPs (GA-CuONPs) and their functionalisation on medical-grade silicone tubing, using an oxysilane bonding agent. The resulting coating shows significant antimicrobial activity against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains, while remaining non-toxic to human cells and exhibiting stable adherence, without leaching. This versatile coating method can be applied during manufacturing, or for ad hoc modifications, enhancing the antimicrobial properties of medical devices.
Background: Equine bedding impacts environmental sustainability and biosecurity. Bedding materials dictate microbial persistence and agricultural waste streams. Miscanthus (Miscanthus giganteus), a low‑input biomass crop, has been proposed as a sustainable alternative to conventional equine bedding. Study aim: Assess the impact of moisture and bacteria upon miscanthus bedding using laboratory models and compare this to other available bedding types.Method: Three miscanthus substrates (chopped, pelleted and chopped with botanical additives) were evaluated for bacterial survival following inoculation with equine pathogens Streptococcus equi subsp. equi and Streptococcus equi subsp. zooepidemicus over 24h. Absorption capacity, early moisture loading (2 h) and long‑term moisture retention (24 h) were quantified and compared with wood shavings, wood pellets and wheat straw.Results: Across all miscanthus substrates, bacterial counts declined modestly but consistently over 24 h, but with no evidence of substrate‑specific antimicrobial activity. Wood shavings contained significantly more moisture (P < 0.0001) than all other bedding substrates tested when assessed 2 h post introduction of liquid. Loose miscanthus substrates contained significantly more moisture than wheat straw (P < 0.001) however, wood shavings retained significantly more moisture than all other bedding substrates tested over 24 h (P < 0.001) This resulted in a wetter bedding surface that may require more frequent replacement and reluctance for important recumbency behaviour in horses. In contrast, miscanthus dried rapidly, maintaining a more comfortable resting surface. Conclusion: Miscanthus represents a bedding material that supports stable hygiene as well as environmental sustainability and could be considered within more sustainable equine management systems.
Antimicrobial resistance and biofilm persistence are major barriers to treating device-associated infections, including catheter-associated urinary tract infections. We evaluated KLS-116, a ruthenium(II) polypyridyl complex, as a next-generation antimicrobial with broad activity against multidrug-resistant uropathogens. KLS-116 showed potent bactericidal effects under physiologically relevant conditions, with minimum inhibitory concentrations ≤ 25 μM (41.8 mg/L) across diverse species. Checkerboard assays demonstrated compatibility with standard antibiotics, yielding indifferent or additive interactions and no antagonism. Importantly, KLS-116 reduced mature biofilms in continuous-flow catheter models and in static models achieved complete clearance at ≥16× MIC after 24 h, outperforming colistin with prolonged exposure. Over 42 days, resistance evolution showed minimal sensitivity shifts, contrasting with rapid ciprofloxacin resistance, indicating a low propensity for resistance. Activity varied with pH, suggesting that the metabolic state influences efficacy. These results position KLS-116 as a promising candidate for CAUTI management and other biofilm-driven infections, guiding future delivery optimization and in vivo validation.
Purpose Urinary tract infections are the most common type of hospital-acquired infection, up to 80% of which are associated with catheterisation. The present study evaluates phenotypic and genomic characterisation of a panel of catheter associated urinary tract infection isolates from a UK hospital. Methods Strains were identified and characterised utilising a range of phenotypic and genomic techniques to understand where methodologies agree. The effect of medium composition on growth and biofilm formation phenotype was also determined to evidence the importance of assay design in characterisation of bacterial isolates. Results No consensus was observed for any of the CAUTI isolates across five identification methods, including biochemical testing, MALDI and sequencing technologies. Comparison of EUCAST antimicrobial susceptibility testing and genotypic data for antibiotic resistance showed high concordance where strains were phenotypically resistant to multiple antibiotic classes, however discordance increased for strains that were phenotypically sensitive to range of antibiotics. Phenotypic analysis of bacterial pathogens often relies on the use of rich laboratory media; however, we observed significant differences in growth rate and biofilm formation within a range of media, with a trend towards comparatively low planktonic growth and significant biofilm biomass formation in artificial urine. Conclusion This study emphasises potential pitfalls of relying on a single method of species identification, with only whole genome sequencing providing accurate identification of isolates to species level. Furthermore, it highlights the continuing importance of utilising phenotypic methods to understand antibiotic resistance within clinical settings and of utilising clinically relevant conditions for pathogen characterisation.