Development of specific and selective bactericide by introducing exogenous metabolite of pathogenic bacteria.

The widespread and repeated use of broad-spectrum bactericides has led to an increase in resistance. Developing novel broad-spectrum bactericides cannot solve the resistance problem, and may even aggravate it. The design of specific and selective bactericides has become urgent. A specific bactericidal design strategy was proposed by introducing exogenous metabolites in this study. This strategy was used to optimize two known antibacterial agents, luteolin (M) and Isoprothiolane (D), against Xoo. Based on the prodrug principles, target compound MB and DB were synthesized by combing M or D with exogenous metabolites, respectively. Bactericidal activity test results demonstrated that while the antibacterial ability of target compounds was significantly improved, their selectivity was also well enhanced by the introducing of exogenous metabolites. Comparing with the original compound, the antibacterial activity of target compound was significantly increased 92.0% and 74.5%, respectively. The optimized target compounds were more easily absorbed, and the drug application concentrations were much lower than those of the original agents, which would greatly reduce environmental pollution and relieve resistance risk. Our proposed strategy is of great significance for exploring the specific and selective bactericides against other pathogens.

An analysis of the mechanism underlying photocatalytic disinfection based on integrated metabolic networks and transcriptional data.

Photocatalytic disinfection has long been used to combat pathogenic bacteria. However, the specific mechanism underlying photocatalytic disinfection and its corresponding targets remain unclear. In this study, an analysis of the potential mechanism underlying photocatalytic disinfection was performed based on integrated metabolic networks and transcriptional data. Two sets of RNA-seq data (wild type and a photocatalysis-resistant mutant mediated by titanium dioxide (TiO2)) were processed to constrain the genome scale metabolic models (GSMM) of E. coli. By analyzing the metabolic network, the differential metabolic flux of every reaction was computed in constrained GSMM, and several significantly differential metabolic fluxes in reactions were extracted and analyzed. Most of these reactions were involved in the transmembrane transport of substances and occurred on the inner membrane or were an important component of the cell membrane. These results, which are consistent with the reported information, validated our analysis process. In addition, our work also identified other new and valuable metabolic pathways, such as the reaction ALCD2x, which has a great effect on the energy production process under bacterial anaerobic conditions. The DHAK reaction is also related to the metabolic process of ATP. These reactions with large differential metabolic fluxes merit further research. Additionally, to provide a strategy to address photocatalysis-resistant mutant bacteria, a metabolic compensation analysis was also performed. The metabolic compensation analysis results provided suggestions for a combined method that can effectively combat resistant bacteria. This method could also be used to explore the mechanisms of drug resistance in other microorganisms.