Polychlorinated biphenyls (PCBs) are a group of colorless and odorless environmental pollutants with a wide range of toxic effects. Some PCBs, especially less chlorinated ones, will rapidly undergo phase I metabolism after entering the body, and hydroxylated polychlorinated biphenyls (OH-PCBs) are the main metabolites of PCBs. Intestinal flora α-glucosidase is a common carbohydrate-active enzyme which is ubiquitous in human intestinal flora. It can convert complex dietary polysaccharides into monosaccharides, assisting the body in degrading complex carbohydrates and providing energy for the survival and growth of bacterial flora. The present study aims to investigate the inhibition of the activity of intestinal flora α-glucosidase by OH-PCBs. 4-Nitrophenyl-α-D-glucopyranoside (PNPG) was used as a probe substrate for α-glucosidase, and in vitro incubation experiments were conducted to study the inhibition of 26 representative OH-PCBs on α-glucosidase. Preliminary screening of in vitro incubation was performed with 100 µM of OH-PCBs. The results showed that 26 OH-PCBs generally exhibited strong inhibition of α-glucosidase. The concentration-dependent inhibition and half inhibition concentrations (IC50s) of OH-PCBs on α-glucosidase were determined. 4'-OH-PCB 86 and 4'-OH-PCB 106 were chosen as representative OH-PCBs, and the inhibition kinetic parameters (Kis) of inhibitors for α-glucosidase were determined. The inhibition kinetic parameters (Kis) of 4'-OH-PCB 86 and 4'-OH-PCB 106 for α-glucosidase are 1.007 µM and 0.538 µM, respectively. The silico docking method was used to further analyze the interaction mechanism between OH-PCBs and α-glucosidase. All these results will help us to understand the risks of OH-PCB exposure from a new perspective.
Ralstonia pickettii, the most critical clinical pathogen of the genus Ralstonia, has been identified as a causative agent of numerous harmful infections. Additionally, Ralstonia pickettii demonstrates adaptability to extreme environmental conditions, such as those found in drinking water. In this study, we conducted a comprehensive genomic analysis to investigate the genomic characteristics related to potential pathogenicity and adaptive evolution in drinking water environments of Ralstonia pickettii. Through phylogenetic analysis and population genetic analysis, we divided Ralstonia pickettii into five Groups, two of which were associated with drinking water environments. The open pan-genome with a large and flexible gene repertoire indicated a high genetic plasticity. Significant differences in functional enrichment were observed between the core- and pan-genome of different groups. Diverse mobile genetic elements (MGEs), extensive genomic rearrangements, and horizontal gene transfer (HGT) events played a crucial role in generating genetic diversity. In drinking water environments, Ralstonia pickettii exhibited strong adaptability, and the acquisition of specific adaptive genes was potentially facilitated by genomic islands (GIs) and HGT. Furthermore, environmental pressures drove the adaptive evolution of Ralstonia pickettii, leading to the accumulation of unique mutations in key genes. These mutations may have a significant impact on various physiological functions, particularly carbon metabolism and energy metabolism. The presence of virulence-related elements associated with macromolecular secretion systems, virulence factors, and antimicrobial resistance indicated the potential pathogenicity of Ralstonia pickettii, making it capable of causing multiple nosocomial infections. This study provides comprehensive insights into the potential pathogenicity and adaptive evolution of Ralstonia pickettii in drinking water environments from a genomic perspective.
