Xi Long,Dali Wang,Zhifen Lin,Mengnan Qin,Chunlei Song,Ying Liu
Organisms in the environment are exposed to mixtures of multiple contaminants, leading to serious environmental harm. These mixtures pose an ecological risk and have attracted an increasing amount of attention; however there has been little in-depth research the toxicity of mixtures, such as antibiotics. To determine how different mixtures of antibiotics affect organisms, the individual and mixture toxicity of sulfonamides and several antibiotics were determined using Escherichia coli as a target organism in our study. The results show that additive effects occur between sulfonamides and quinolones or with a portion of β-lactams, synergistic effects appear between sulfonamides and their potentiators or cefotaxime sodium, and antagonistic effects arise between sulfonamides and tetracyclines or penicillin V potassium salt. In addition, the toxicity mechanism of binary mixtures is further discussed and the results reveal that the joint effect differences depend not only the target proteins of individual chemicals but also on their effective combined concentration based on the approach of Quantitative Structure Activity Relationships (QSARs) and molecular docking. This study introduces the concept of the “effective concentration” to provide insight into understanding the mechanism of binary mixtures, which will be beneficial for evaluating the ecological risk of antibiotics.
Escherichia coli strain Nissle 1917 (EcN) has been widely shown to effectively treat inflammatory bowel diseases (IBDs). Unfortunately, after oral administration, EcN viability dramatically decreases due to severe environmental factors, including low gastric pH, temperature and osmotic pressure. To address these challenges and improve oral bio-availability, this study utilized layer-by-layer assembly (LbL) and ionic cross-linking with CaCl 2 as a method of EcN encapsulation (GEcN). Upon examination, GEcN cells were shown to maintain their ability to grow and proliferate, but had a slightly longer stationary phase (10 h) relative to free EcN (4 h). When exposed to simulated gastric fluid (SGF), a higher number of GEcN cells survived up to 12 h when compared to the other groups. To assess the therapeutic effect of EcN encapsulation in vivo , a TNBS-induced colitis rat model was established. When compared with the oral administration of free EcN, GEcN exhibited a significantly enhanced anti-inflammatory effect. Furthermore, GEcN treatment showed a lower disease activity index (DAI), decreased pro-inflammatory cytokine expression (MPO, TNF-α, IL-6) and increased anti-inflammatory cytokine expression (IL-10). Additionally, rats that received GEcN had much higher ZO-1 expression levels. These results suggest that EcN encapsulation in a chitosan―alginate matrix when utilizing the LbL assembly with CaCl 2 cross-linking can improve probiotic viability in a gastric environmental and thereby offer a more effective treatment for IBDs.
Background The emergence of carbapenem and colistin co-resistant Escherichia coli poses a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in E. coli strains.Methods Antimicrobial susceptibility test was carried out by agar dilution methods and colistin resistance was confirmed by broth microdilution methods. Whole genome sequencing was carried out, and resistance genes, sequence types and virulence genes of carbapenems and colistin co-resistance E. coli isolates were analyzed.Results The results showed that among the 176 carbapenem-resistant Enterobacteriaceae strains, 5 multidrug resistant E. coli strains exhibiting coresistance to carbapenem and colistin. The main mechanism of 5 E. coli strains in this study was generating carbapenem. Four E. coli strains were mcr-positive, while one mcr-negative strain had a new MgrB mutation. The blaNDM-5, blaCTX-M-65, blaOXA-10, blaTEM-1 and mcr-1.1 genes were simultaneously detected in E. coli 20IR1127 strain belonging to ST156 lineage. Other antimicrobial resistance genes encoding aminoglycosides-, sulfonamide-, chloramphenicol-, tetracyclines- and macrolides resistance were also detected.Conclusion The main mechanisms of carbapenem and colistin resistance were encoded by blaNDM and mcr1.1, meanwhile mgrB mutations also contribute to colistin resistance. To our knowledge, this study is the first to report of E. coli ST156 strain in which the blaNDM-5, blaCTX-M-65, blaOXA-10, blaTEM-1 and mcr1.1 genes coexist. In addition, there is also an E. coli ST457 strain, which carries blaTEM-1, blaNDM-9, blaCTX-M-199 and is positive for mcr1.1 gene.
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