The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Methyltransferase Contingencies in the Pathway of Everninomicin D Antibiotics and Analogues

Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A₁, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A₁- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A₁-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates.     

分离膜中的新成员——纳滤膜及其在制药工业中的应用

介绍了“纳滤膜”名称的由来，该膜的分离机理和性能，简述了纳滤技术在发酵医药产品生产中液体分离方面的几例应用     

Distribution and Fate of Escherichia coli in Lake Michigan Following Contamination with Urban Stormwater and Combined Sewer Overflows

Escherichia coli distribution and persistence in nearshore Lake Michigan were assessed following heavy rains and sanitary sewer overflow (SSO) and combined sewer overflow (CSO) events over a 5-year period, including an 18-day period following 25.4 cm of rainfall in which intensive studies were conducted following multiple CSO and SSO events. E. coli levels in the Milwaukee estuary and harbor following SSO and CSO events ranged from 10⁴ to nearly 10⁵ CFU/100 mL, which were significantly higher (p ≤ 0.05) than levels following rainfall alone. Sites outside of the breakwall but within the contamination plume (e.g., within 2 km of the harbor) were an order of magnitude lower. Locations 2–5 km from the harbor ranged from below detection limits, of < 1 to 5 CFU/100 mL. E. coli levels corrected for dilution based on specific conductivity measurements were lower than what would be expected for loss due to dilution alone, suggesting a combination of die-off and dilution, were responsible for the rapid disappearance of these organisms outside of the harbor. E. coli and fecal coliforms measured concurrently demonstrated that fecal coliforms could be recovered longer than E. coli in the open waters of the lake. E. coli isolated directly from sewage treatment plant influent were found to have a marked increase in antibiotic resistance traits for ten antibiotics commonly used in the human population compared with isolates from two animal sources of fecal pollution. However, E. coli obtained from sewage impacted water (n = 2,513) and from stormwater impacted water (n = 1,465) collected the previous year when there were no sewage overflows, were found to have no significant difference (p < 0.05) in the frequency of resistance when comparing the two conditions. E. coli survival characteristics and population dynamics are most likely influenced by multiple factors in complex systems such as the watershed/estuarine/lake environments of the Great Lakes.     

(S)-Reutericyclin: Susceptibility Testing and In Vivo Effect on Murine Fecal Microbiome and Volatile Organic Compounds

We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile.     

纳米TiO2改性聚乙烯膜抗菌性能的研究

采用纳米粉体的分散技术和掺混技术，在聚乙烯中加入纳米TiO2制得纳米TiO2改性聚乙烯膜，并对该膜的抗菌性、抗变色性、使用安全性进行了研究。结果表明，纳米TiO2改性聚乙烯膜具有良好的抗菌性能，在不同光源条件下对不同微生物菌株的杀菌率都达到92％以上，且具有抗菌广谱、长效、安全稳定等性能。     

美洛西林钠的合成

美洛西林钠是一种新型半合成青霉素。在以往的文献中其合成过程中都要使用剧毒品光气作为反应物。今以2-咪唑烷酮为起始原料，经甲磺酰化、酰化等四步反应，合成了酰脲类青霉素美洛西林钠。在合成过程中用氯甲酸三氯甲酯替代光气对其重要中间体l-氯甲酰基-3-甲磺酰基-2-咪唑烷酮的合成工艺进行了改进，不仅避免了使用光气，而且收率也从文献值70％提高到75％。     

纳米TiO2在塑料中的抗菌性能研究

本文利用纳米TiO2作为无机抗菌填料，研制抗菌杀毒、表面自洁功能的塑料，其杀菌性能达到97％以上。探讨了纳米TiO2填料的杀菌性能影响因素及其杀菌广谱性。     

医院内抗生素耐药性传染的稳定性与Hopf分支

研究了医院内感染的带有非线性发生率的抗生素耐药性的时滞传染病模型的稳定性.确定了疾病暴发的阈值R0,运用Lasalle-Liapunov不变集原理和Routh-Hurwitz判据得到了,当R01时无病平衡点是全局稳定的;当R01时,地方病平衡点存在且唯一,对于任意的τ≠0,总能得到在地方病平衡点处的Hopf分支存在的条件.最后通过数值模拟验证了结论的正确性.