Coexistence of antibiotic resistance genes, fecal bacteria, and potential pathogens in anthropogenically impacted water.

Microbial indicators are often used to monitor microbial safety of aquatic environments. However, information regarding the correlation between microbial indicators and ecotoxicological factors such as potential pathogens and antibiotic resistance genes (ARGs) in anthropogenically impacted waters remains highly limited. Here, we investigated the bacterial community composition, potential pathogens, ARGs diversity, ARG hosts, and horizontal gene transfer (HGT) potential in urban river and wastewater samples from Chaohu Lake Basin using 16S rRNA and metagenomic sequencing. The composition of the microbial community and potential pathogens differed significantly in wastewater and river water samples, and the total relative abundance of fecal indicator bacteria was positively correlated with the total relative abundance of potential pathogens (p < 0.001 and Pearson's r = 0.758). Network analysis indicated that partial ARG subtypes such as dfrE, sul2, and PmrE were significantly correlated with indicator bacteria (p < 0.05 and Pearson's r > 0.6). Notably, Klebsiella was the indicator bacteria significantly correlated with 4 potential pathogens and 14 ARG subtypes. ARGs coexisting with mobile gene elements were mainly found in Thauera, Pseudomonas, Escherichia, and Acinetobacter. Next-generation sequencing (NGS) can be used to conduct preliminary surveys of environmental samples to access potential health risks, thereby facilitating water resources management.

Excretion, Metabolism and Cytochrome P450 Inhibition of Methyl 3,4-Dihydroxybenzoate (MDHB): A Potential Candidate to Treat Neurodegenerative Diseases.

BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work investigated its excretion, metabolism, and cytochrome P450-based drug-drug interactions (DDIs). METHODS: After intragastric administration of MDHB, the parent drug was assayed in the urine and faeces of mice. Metabolites of MDHB in the urine, faeces, brain, plasma and liver were detected by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A cocktail approach was used to evaluate the inhibition of cytochrome P450 isoforms by MDHB. RESULTS: The cumulative excretion permille of MDHB in the urine and faeces were found to be 0.67 ± 0.31 and 0.49 ± 0.44‰, respectively. A total of 96 metabolites of MDHB were identified, and all IC50 (half-maximal inhibitory concentration) values of MDHB towards cytochrome P450 isoforms were > 100 µM. CONCLUSIONS: The results suggest that MDHB has a low parent drug cumulative excretion percentage and that MDHB has multiple metabolites and is mainly metabolized through the loss of -CH2 and -CO2, the loss of -CH2O, ester bond hydrolysis, the loss of -O and -CO2, isomerization, methylation, sulfate conjugation, the loss of -CH2O and -O and glycine conjugation, glycine conjugation, the loss of two -O groups and alanine conjugation, the loss of -CH2O and -O and glucose conjugation, glucuronidation, glucose conjugation, etc., in vivo. Finally, MDHB has a low probability of cytochrome P450-based DDIs.