Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.

Proton radiation effects on carrier transport in diamond radiation detectors.

Diamond, a highly radiation-resistant material, is considered a nearly ideal material for radiation detection, particularly in high-energy physics. In this study, radiation damage from high-energy proton beams was induced in diamond crystals to determine exposure lifetime in detectors made from this material; the effects were investigated using non-destructive x-ray techniques and through the FLUKA simulation package. Two diamond detectors were irradiated by an 800 MeV proton beam at different fluence rates, and the real-time current response was recorded to observe degradation in the signal over time. It was determined that the proton fluence rate had a significant effect on the device degradation. The detector performance from the irradiated detectors was characterized using x-ray beam-induced current measurements, and the mechanism of proton radiation damage to diamond sensors, especially the radiation effects on carrier transport, was studied. The vacancies generated from proton irradiation were considered the major source of detector degradation by trapping holes and inducing an internal electric field. Simulation results from the FLUKA package revealed an uneven distribution of the radiation-induced vacancies along the beam path, and the corresponding detector signals calculated from the simulation results displayed a good match to the experimental results.

[Molecular characterization of vancomycin-resistant Enterococci].

OBJECTIVE: To investigate the homology and resistant mechanism of vancomycin-resistant Enterococci (VRE) isolates. METHODS: A total of 9 VRE isolates were collected from 2006 to 2007 at PUMC hospital. The susceptibility of these isolates to 10 different antibiotics including vancomycin was tested by E-test. These strains were processed by brain heart infusion agar screening in the presence of vancomycin (6 microg/ml), and were analyzed for genotypic characteristics using the multiplex PCR. The homology of the isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: All the 9 VRE isolates were identified as Enterococci faecium. The visual analysis of PFGE patterns revealed 6 different PFGE types. The vanA gene was confirmed by PCR and sequencing in 9 VRE isolates, which were consistent between phenotype and genotype for glycopeptides resistance. CONCLUSIONS: Only vanA genotype was detected in PUMC hospital. Clonal dissemination, horizontal gene transfer, and the selective pressure of antimicrobial agents may contribute to the increase of VRE.

[Sutureless lamellar keratoplasty by microkeratome combined with fibrin tissue adhesive in rabbits].

OBJECTIVE: To evaluate the feasibility and safety of sutureless lamellar keratoplasty by microkeratome combined with fibrin tissue adhesive. METHODS: Twenty-four New Zealand white rabbits were divided into two groups, the donor grafts and recipient beds were made by the microkeratome, the grafts were glued over the stoma bed using the commercial product Tisseel in one group; and grafts without tissue adhesive were used as the control group. Corneal refractive power was measured by automated keratometer preoperatively and in 3 days, 2 weeks, 1 and 3 months postoperatively. Rejection and cornea transparency were observed. Confocal microscopy was used to observe corneal wound healing response and to measure the keratocyte and endothelium densities in vivo. Corneal wound healing was also evaluated using light and fluorescence microscopy. RESULTS: Ninety-two percent (11/12 eyes) of the glued grafts were retained in the Tisseel group, whereas all grafts were lost in the control group. All survived grafts were clear 1 month after surgery. However, in the control group, severe haze in the grafts occurred 2 weeks postoperatively. Confocal microscopy showed that there was a significant decrease of the keratocyte density surrounding the lenticule-host interface, and no changes occurred in the posterior keratocyte and endothelium. Histopathologic observations demonstrated the presence of a line of amorphous eosinophilic substance in the lenticule-host interface at 3 days after surgery, but the line disappeared after 1 month. Fluorescence microscopy showed no detectable regenerated stromal tissue. CONCLUSIONS: This initial study demonstrates sutureless optical lamellar keratoplasty performed by microkeratome combined with fibrin tissue adhesive is a simple and safe technique. Stromal wound healing response to this surgery is minimal. Fibrin tissue adhesive has no influence on the cornea optical property.