Furazolidone

Ofloxacin (OFL) is an effective antibiotic against bacteria.However, the overuse of ofloxacin can lead to residues in animal-derived foods, posing a potential threat to human health.Due to the issue of false positives in single-mode detection, it is crucial to establish a multi-mode method for accurate and sensitive detection of ofloxacin.Peroxidase-like active iron-nickel bimetallic organic framework (FeNi-MOF) and orange fluorescent carbon dots (OCDs) synthesized by a simple one-pot method were used to establish a dual-mode colorimetric/ratiometric fluorescence biosensor for the detection of ofloxacin residues.In colorimetric mode, in the presence of hydrogen peroxide (H₂O₂), FeNi-MOF can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to produce blue oxTMB.However, the fluorescence of OCDs at 588 nm will be quenched by oxTMB, thus forming a ratiometric fluorescence signal with the fluorescence of FeNi-MOF at 420 nm.The linear range of the dual-mode detection method was 10^-7-10^-7 mg/mL, and the detection limits were 1.1 ng/kg (colorimetric) and 0.34 ng/kg (radiometric fluorescence).In addition, the constructed smartphone sensing platform is also well applied for on-site portable detection.Therefore, we have established a dual-mode sensor with high specificity, accuracy, and excellent anti-interference ability for OFL detection, and satisfactory results are also obtained in the actual spiked samples.

The combined application of furazolidone and vancomycin has previously been shown to be synergistic against Gram-negative pathogens, with great therapeutic promise. However, the emergence and mechanism of resistance to this antibiotic combination have not been characterized. To fill this gap, we here selected Escherichia coli progeny for growth on the furazolidone–vancomycin combination at the concentration where the parent was sensitive. We show that selected clones were associated with increased resistance to neither, only one drug, or both furazolidone and vancomycin, but in all cases were associated with a decrease in the growth inhibition synergy. Using whole-genome sequencing, we identified various gene mutations in the resistant mutants. We further investigated the mechanism behind the most frequently arising mutations, those in the riboflavin biosynthesis genes ribB and ribE, that represent novel mutations causing furazolidone resistance and diminished vancomycin–furazolidone synergy. It was found that these ribB/ribE mutations act predominantly by decreasing the activity of the NfsA and NfsB nitroreductases. The emergence of the ribB/ribE mutations imposes a significant fitness cost on bacterial growth. Surprisingly, supplementing the medium with riboflavin, which compensates for the affected riboflavin biosynthesis pathway, could restore the normal growth of the ribB/ribE mutants while having no effects on the furazolidone resistance phenotype. Searching the ribB/ribE mutations in the public sequencing database detects the presence of the furazolidone-resistance-conferring ribE mutations (TKAG131–134 deletion or duplication) in clinical isolates from different countries. Hypotheses explaining why these ribE mutations were found in clinical isolates despite having poor fitness were further discussed.