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.     

石油降解菌ZS1对典型抗生素毒害作用的应激响应机制

为了解抗生素对石油降解菌的生态效应及微生物对典型抗生素毒害作用的应激响应机制，通过开展不同浓度典型抗生素对高效石油降解菌铜绿假单胞菌（ZS1）的毒性试验，研究了菌体细胞在3种不同种类抗生素（土霉素、红霉素、磺胺嘧啶）作用下的生长及毒理指标。结果表明，3种抗生素对ZS1有不同的抑菌效果，其中土霉素对ZS1活性的抑制程度最强，抑制率随着土霉素浓度的增大而明显上升，有显著的浓度-效应关系。研究了ZS1抗氧化酶（过氧化氢酶、过氧化物酶、超氧化物歧化酶）对抗生素的响应机制，结果表明ZS1受到污染时会通过产生抗氧化酶抵抗外界污染并维持细胞功能。     

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.     

硅量子点荧光传感器快速检测鲜奶中的四环素

建立以硅量子点(silicon quantum dot,SiQDs)为荧光传感器快速检测四环素的新方法,以N-(β-氨乙基)-γ-氨丙基甲基二甲氧基硅烷为硅源,柠檬酸为还原剂,采用水热法合成SiQDs;通过透射电镜(transmission electron microscope,TEM)和光谱分析法研究其形貌结构和光学特性;利用四环素能有效地猝灭SiQDs荧光,构建荧光传感器用于四环素检测。结果显示,所制备的SiQDs呈球形、稳定性高,水溶性好。在优化的实验条件下,方法的线性范围为0.05~90μmol/L,检出限为18 nmol/L,用于生鲜牛奶样品测定,加标回收率为92.36%~104.07%。该方法简便、快速、灵敏,适于鲜奶中四环素的准确测定。     

Second-Generation Meridianin Analogues Inhibit the Formation of Mycobacterium smegmatis Biofilms and Sensitize Polymyxin-Resistant Gram-Negative Bacteria to Colistin

Drug-resistant bacteria are rapidly becoming a significant problem across the globe. One element that factors into this crisis is the role played by bacterial biofilms in the recalcitrance of some infections to the effects of conventional antibiotics. Bacteria within a biofilm are highly tolerant of both antibiotic treatment and host immune responses. Biofilms are implicated in many chronic infections, including tuberculosis, in which they can act as bacterial reservoirs, requiring an arduous antibiotic regimen to eradicate the infection. A separate, compounding problem is that antibiotics once seen as last-resort drugs, such as the polymyxin colistin, are now seeing more frequent usage as resistance to front-line drugs in Gram-negative bacteria becomes more prevalent. The increased use of such antibiotics inevitably leads to an increased frequency of resistance. Drugs that inhibit biofilms and/or act as adjuvants to overcome resistance to existing antibiotics will potentially be an important component of future approaches to antibacterial treatment. We have previously demonstrated that analogues of the meridianin natural product family possess adjuvant and antibiofilm activities. In this study, we explore structural variation of the lead molecule from previous studies, and identify compounds showing both improved biofilm inhibition potency and synergy with colistin.