Isoprenoid Biosynthesis Inhibitors Targeting Bacterial Cell Growth

We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron‐withdrawing aryl‐alkyl side chains which inhibited the growth of Gram‐negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa) at ～1–4 μg mL^?1 levels. They were found to be potent inhibitors of FPPS; cell growth was partially “rescued” by the addition of farnesol or overexpression of FPPS, and there was synergistic activity with known isoprenoid biosynthesis pathway inhibitors. Lipophilic hydroxyalkyl phosphonic acids inhibited UPPS and UPPP at micromolar levels; they were active (～2–6 μg mL^?1) against Gram‐positive but not Gram‐negative organisms, and again exhibited synergistic activity with cell wall biosynthesis inhibitors, but only indifferent effects with other inhibitors. The results are of interest because they describe novel inhibitors of FPPS, UPPS, and UPPP with cell growth inhibitory activities as low as ～1–2 μg mL^?1.     

Gramicidin A Mutants with Antibiotic Activity against Both Gram‐Positive and Gram‐Negative Bacteria

Antimicrobial peptides (AMPs) have shown potential as alternatives to traditional antibiotics for fighting infections caused by antibiotic‐resistant bacteria. One promising example of this is gramicidin A (gA). In its wild‐type sequence, gA is active by permeating the plasma membrane of Gram‐positive bacteria. However, gA is toxic to human red blood cells at similar concentrations to those required for it to exert its antimicrobial effects. Installing cationic side chains into gA has been shown to lower its hemolytic activity while maintaining the antimicrobial potency. In this study, we present the synthesis and the antibiotic activity of a new series of gA mutants that display cationic side chains. Specifically, by synthesizing alkylated lysine derivatives through reductive amination, we were able to create a broad selection of structures with varied activities towards Staphylococcus aureus and methicillin‐resistant S. aureus (MRSA). Importantly, some of the new mutants were observed to have an unprecedented activity towards important Gram‐negative pathogens, including Escherichia coli, Klebsiella pneumoniae and Psuedomonas aeruginosa.     

壳聚糖在抗菌PP中的应用

通过热重分析、差示扫描量热法对壳聚糖的热稳定性进行了研究,考察了其在抗菌聚丙烯(PP)中应用的可行性。壳聚糖在氧气中起始分解温度为252.0℃,可满足加工PP时对耐热性能的要求。壳聚糖改性PP的流动性和力学性能变化不大,黄色指数增加。随着壳聚糖添加量的增加,抗菌率逐渐提高,当壳聚糖质量分数达3%时,抗菌PP对大肠杆菌和金黄葡萄球菌的杀菌率均可达99%。     

一项微生物能力验证的多种方法检测结果分析

为确保微生物能力验证结果的准确报出,本实验室采用了多种方法进行CNAS T 0710的铜绿假单胞菌(Pseudomonas aeruginosa)和金黄色葡萄球菌(Staphylococcus aureus)的能力验证比对检验,结果表明:以上多种检测方法的测试结果相吻合,均显示5份样品中有2份检出铜绿假单胞菌,2份检出金黄色葡萄球菌。最终5份样品测试均取得满意结果,在分析比较中也总结出各种检验方法的优缺点。     

湄潭白茶多糖对金黄色葡萄球菌的抑菌活性及其稳定性

目的:研究湄潭白茶多糖对金黄色葡萄球菌的体外抑菌活性及其稳定性.方法:采用牛津杯法和微量肉汤稀释法测定湄潭白茶多糖对金黄色葡萄球菌的抑菌活性及最小抑菌浓度(Minimum inhibitory concentration,MIC),并进一步探讨温度、pH、紫外线照射和金属离子对其抑菌活性稳定性的影响.结果:湄潭白茶多糖...     

Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?

The main purpose of this review is to present justification for the urgent need to implement specific prophylaxis of invasive Staphylococcus aureus infections. We emphasize the difficulties in achieving this goal due to numerous S. aureus virulence factors important for the process of infection and the remarkable ability of these bacteria to avoid host defense mechanisms. We precede these considerations with a brief overview of the global necessitiy to intensify the use of vaccines against other pathogens as well, particularly in light of an impasse in antibiotic therapy. Finally, we point out global trends in research into modern technologies used in the field of molecular microbiology to develop new vaccines. We focus on the vaccines designed to fight the infections caused by S. aureus, which are often resistant to the majority of available therapeutic options.     

传统发酵食品中分离的乳酸菌粗提物对耐甲氧西林金黄色葡萄球菌抑菌机制研究

目的 探究乳酸菌HS011(LactobacillusplantarumMG5276)、德氏乳杆菌保加利亚亚种HS023(Lactobacillus delbrueckii subsp. Bulgaricus strain NDO4)、嗜热链球菌HS033 (Streptococcus thermophilus 3233)对耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA)的抑菌机制。方法 以MRSA为研究对象,探索乳酸菌粗提物对MRSA菌株的最小抑菌浓度(minimum inhibitory concentration, MIC)的影响、抗菌药物复合作用对细菌生长的影响、抽提物对MRSA生物被膜抑制和清除效果,以及抽提物对MRSA细胞膜完整性的破坏作用等。结果 乳酸菌粗提物HS011、HS023、HS033对MRSA的MIC分别为5.75、5.00、6.00mg/mL;指示菌MRSA的生长过程受到粗提物明显抑制,在6h时HS011、HS023、HS033对MRSA的抑菌率分别为28.69%、69.20%和42...     

Biofilm and Small Colony Variants—An Update on Staphylococcus aureus Strategies toward Drug Resistance

Recently, the drawbacks arising from the overuse of antibiotics have drawn growing public attention. Among them, drug-resistance (DR) and even multidrug-resistance (MDR) pose significant challenges in clinical practice. As a representative of a DR or MDR pathogen, Staphylococcus aureus can cause diversity of infections related to different organs, and can survive or adapt to the diverse hostile environments by switching into other phenotypes, including biofilm and small colony variants (SCVs), with altered physiologic or metabolic characteristics. In this review, we briefly describe the development of the DR/MDR as well as the classical mechanisms (accumulation of the resistant genes). Moreover, we use multidimensional scaling analysis to evaluate the MDR relevant hotspots in the recent published reports. Furthermore, we mainly focus on the possible non-classical resistance mechanisms triggered by the two important alternative phenotypes of the S. aureus, biofilm and SCVs, which are fundamentally caused by the different global regulation of the S. aureus population, such as the main quorum-sensing (QS) and agr system and its coordinated regulated factors, such as the SarA family proteins and the alternative sigma factor σB (SigB). Both the biofilm and the SCVs are able to escape from the host immune response, and resist the therapeutic effects of antibiotics through the physical or the biological barriers, and become less sensitive to some antibiotics by the dormant state with the limited metabolisms.     

Comparison of Automated Ribotyping,spa Typing,and MLST in 108 Clinical Isolates of Staphylococcus aureus from Orthopedic Infections

108 isolates of Staphylococcus aureus, belonging to six large ribogroups according to the automated Ribo-Printer^® system, were studied with two highly used molecular methods for epidemiological studies, namely multi-locus sequence typing (MLST) and spa typing, followed by BURP and eBURST v3 analysis for clustering spa types and sequence (ST) types. The aim was to evaluate whether automated ribotyping could be considered a useful screening tool for identifying S. aureus genetic lineages with respect to spa typing and MLST. Clarifying the relationship of riboprinting with these typing methods and establishing whether ribogroups fit single clonal complexes were two main objectives. Further information on the genetic profile of the isolates was obtained from agr typing and the search for the mecA, tst genes, and the IS256 insertion sequence. Automated ribotyping has been shown to predict spa clonal complexes and MLST clonal complexes. The high cost and lower discriminatory power of automated ribotyping compared to spa and MSLT typing could be an obstacle to fine genotyping analyzes, especially when high discriminatory power is required. On the other hand, numerous advantages such as automation, ease and speed of execution, stability, typeability and reproducibility make ribotyping a reliable method to be juxtaposed to gold standard methods.