Novel antibacterial modalities against methicillin resistant Staphylococcus aureus derived from plants

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious bacterial pathogen that induces high mortality and morbidity. Due to the emergence of multiple resistance, antibiotic treatments are rapidly becoming ineffective for the related infections. Natural products, especially those derived from plants, have been proven to be effective agents with unique antibacterial properties through different mechanisms. This review interprets the resistance mechanisms of MRSA with the aim to conquer public health threat. Further, recent researches about plant antimicrobials that showed remarkable antibacterial activity against MRSA are recorded, including the crude plant extracts and purified plant-derived bioactive compounds. Novel anti-MRSA modalities of plant antimicrobials such as alteration in efflux pump, inhibition of pyruvate kinase, and disturbance of quorum sensing in MRSA are also summarized which may be promising alternatives to antibacterial drug development in future.     

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.     

弹载斜视FMCW-SAR的改进距离堆栈算法

分析了弹载斜视FMCW-SAR的成像几何关系,建立了其点目标回波信号模型和推导了回波信号的二维波数域形式.大斜视情况下,二次以上的高次距离方位耦合项不能忽略,所以FMCW-SAR中常用的改进频率变标算法不再适用.提出的距离堆栈改进算法在聚焦深度范围内利用相同的斜距值进行距离堆栈操作,其计算效率提高了2D2f*/( 1.57cλ)倍.与改进的频率变标算法相比,不同斜视角仿真实验的结果验证所提算法的有效性和正确性.     

耐甲氧西林金黄色葡萄球菌裂解性噬菌体PhMASA-WJ的生物学特性及其对小鼠败血症的疗效

目的探讨耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)噬菌体PhMASA-WJ的生物学特性及其对小鼠败血症的疗效,为开发高效低毒的抗菌药物奠定实验基础。方法以MRSA(USA300)为宿主菌,从地下污水中分离筛选出1株噬菌体PhMASA-WJ,双层琼脂平板培养法测定噬菌体效价,点滴法测定噬菌体裂解谱,确定最佳感染复数(multiplicity of infection,MOI),提取噬菌体全基因组并进行酶切鉴定,电镜观察噬菌体形态,并检测噬菌体的体外裂解效果、安全性及其对小鼠败血症的疗效。结果 PhMASA-WJ在USA300菌苔上形成直径1～2 mm的圆形、透明且边界清晰的噬菌斑,PhMASA-WJ效价为7. 1×10⁸ PFU/m L,其为专一裂解金黄色葡萄球菌的噬菌体,最佳MOI为0. 001,属于RNA病毒,基因组大小约23 000 bp。电镜观察显示,PhMASA-WJ属于有尾噬菌体目肌尾噬菌体科。动物实验证实,PhMASA-WJ对小鼠无毒副作用,败血症小鼠经PhMASA-WJ...     

Modeling the transmission of livestock associated methicillin-resistant Staphylococcus aureus along the pig slaughter line

The study introduces a new approach for a qualitative transmission assessment of MRSA throughout the pig slaughter process. Based on prevalence data found in literature the MRSA contamination and elimination rates of each individual slaughter step were estimated. The rates were used to set up a Monte Carlo simulation for modeling the propagation of MRSA along the process chain and to quantify the impact of a variable initial prevalence on the outcome prevalence of the carcasses. Sensitivity analyses for the model as well as three different scenarios were performed to estimate the impact of cross contamination during slaughter and to determine the process stages where hygiene interventions are most effective.Regardless of the initial extent of MRSA contamination low outcome prevalences ranging between 0.15 and 1.15% were achieved among pig carcasses indicating that the pig slaughter chain generally includes process steps with the capacity to limit carcass contamination. Especially scalding and singeing can lead to a significant reduction of superficial MRSA contamination during the first half of the slaughter process. Nevertheless, scenario analyses showed that the low MRSA outcome prevalence can only be guaranteed if recontamination during the ongoing slaughter process is obviated. In order to ensure a low MRSA load on pig carcasses at the end of slaughter the abattoir should primarily concentrate on controlling the process parameters of scalding and singeing and avoiding recontamination at subsequent process steps.