Temperature dependence of the thermal boundary resistivity of glass-embedded metal nanoparticles

The temperature dependence of the thermal boundary resistivity is investigated in glass-embedded Ag particles of radius 4.5 nm, in the temperature range from 300 to 70 K, using all-optical time-resolved nanocalorimetry. The present results provide a benchmark for theories aiming at explaining the thermal boundary resistivity at the interface between metal nanoparticles and their environment, a topic of great relevance when tailoring thermal energy delivery from nanoparticles as for applications in nanomedicine and thermal management at the nanoscaleComment: 4 pages, 3 figure

The molecular basis of antibiotic treatment failure in chronic urinary tract infections

Urinary tract infections (UTIs) are amongst the most common infections worldwide, and are becoming increasingly difficult to treat. In addition to the acceleration of classic antimicrobial resistance, recurrence after initial resolution is common. Our clinical experience is that chronically infected patients sometimes fail to respond to antibiotics predicted to be effective from culture-based sensitivity testing, while antibiotics predicted to be unsuitable can succeed. We hypothesized that the bladder environment could lead to differential bacterial gene expression, resulting in differences in minimum inhibitory concentration (MICs) compared with standard culture. Here, using strains of Escherichia coli evolved in the lab to be resistant to amoxicillin–clavulanic acid, we present data that MICs differ depending on which media the assay is performed in (M9, ISO, LB, human urine), as well as in urine-containing supernatant enriched from urothelial organoids. Next, we examined the behaviour of patient-derived Enterococcus faecalis, one of the main causative agents of chronic UTIs in the elderly. We are in the process of evaluating the MIC of first-line UTI antibiotics using growth media supplemented with urine, to more closely mimic the native uropathogen environment. Moreover, we are characterising the resistance genes expressed in those differing environments using next generation sequencing technology and comparing the results with those obtained from bacteria grown on standard diagnostic media. Our work demonstrates the danger of extrapolating biological behaviour from artificial culture substrates and may lead to better diagnostic tests and treatments for chronic UTI

Effect of the urine micro-environment on the genome, evolution and behaviour of strains of Enterococcus involved in treatment-resistant urinary tract infection

Urinary tract infections (UTIs) are common. Despite antibiotic treatment, they often recur, and some infections persist, causing life-threatening complications. Consequently, UTI is a common reason for antibiotic prescription, worsening the antimicrobial resistance (AMR) crisis. Infections caused by Enterococcus spp. are common in certain settings, including in hospitals and amongst the elderly, but are little studied. Using a combination of genomics, microscopy and microbiology, I aimed to understand more about the biology of two Enterococcus species in the context of UTI. First, I performed a phylogenetic study to delineate the population structure of Enterococcus faecalis and Enterococcus faecium from public repositories alongside the lab’s clinical isolates. I also performed a pan-genome-wide association study of AMR genes. My results supported the presence of little genetic diversity among human-associated E. faecalis and E. faecium isolates. Second, I created urine-containing media to better mimic the complexity of the urinary tract, performed growth assays and tested the minimum inhibitory concentration (MIC) of different antibiotics on Enterococcus. While nitrofurantoin did not show MIC differences with urine, amoxicillin exhibited a strong urine effect. Consequently, I identified five putative β-lactamase-encoding genes in E. faecalis. Lastly, I used microscopy and RNAseq to determine how urine affects E. faecalis. Scanning electron microscopy did not show significant differences in morphology when bacteria were grown in urine. However, a pilot RNAseq experiment revealed differentially expressed metabolic genes, especially those involved in sugar transport. Additionally, I found differential expression levels of three putative β-lactamase genes. In conclusion, with the combination of omics and microbiology, I showed that E. faecalis exhibits unique adaptive features to the urinary tract, elucidating aspects that may inform the development of new diagnostic tools