Mechanisms of nisin resistance in Gram-positive bacteria

Nisin is the most prominent lantibiotic and is used as a food preservative due to its high potency against certain Gram-positive bacteria. However, the effectiveness of nisin is often affected by environmental factors such as pH, temperature, food composition, structure, as well as food microbiota. The development of nisin resistance has been seen among various Gram-positive bacteria. The mechanisms under the acquisition of nisin resistance are complicated and may differ among strains. This paper presents a brief review of possible mechanisms of the development of resistance to nisin among Gram-positive bacteria.     

Lipidated α/Sulfono-α-AA heterogeneous peptides as antimicrobial agents for MRSA

Though antibiotics have been used for decades to treat bacterial infections, there is a great need for new treatment methods. Bacteria are becoming resistant to conventional antibiotics, as is the case with Methicillin resistant Staphylococcus aureus (MRSA). Herein we report the design of a series of lipidated α/Sulfono-α-AA heterogeneous peptides as mimics for Host Defense Peptides (HDPs). Utilizing fluorescence microscopy and depolarization techniques, our compounds demonstrate the ability to kill Gram-positive bacteria through cell membrane disruption. This mechanism of action makes it difficult for bacteria to develop resistance. Further time kill studies and hemolytic assays have also proven these compounds to be efficient in their ability to eradicate bacteria cells while remaining non-toxic to human red blood cells. This new class of peptidomimetics shows promise for the future antibiotic treatment of MRSA.     

New potentiators of ineffective antibiotics: Targeting the Gram-negative outer membrane to overcome intrinsic resistance

Because of the rise in antibiotic resistance and the dwindling pipeline of effective antibiotics, it is imperative to explore avenues that breathe new life into existing drugs. This is particularly important for intrinsically resistant Gram-negative bacteria, which are exceedingly difficult to treat. The Gram-negative outer membrane (OM) prevents the entry of a plethora of antibiotics that are effective against Gram-positive bacteria, despite the presence of the targets of these drugs. Uncovering molecules that increase the permeability of the OM to sensitize Gram-negative bacteria to otherwise ineffective antibiotics is an approach that has recently garnered increased attention in the field. In this review, we survey chemical matter which has been shown to potentiate antibiotics against Gram-negative bacteria by perturbing the OM. These include peptides, nanoparticles, macromolecules, antibiotic conjugates, and small molecules.     

The threat of antibiotic resistance in Gram-negative pathogenic bacteria: beta-lactams in peril!

Beta-lactam antibiotics are the cornerstone of our antibiotic armamentarium. By inhibiting bacterial cell wall synthesis, they are highly effective against Gram-positive and Gram-negative bacteria. Unfortunately, bacteria have evolved sophisticated resistance mechanisms to combat the lethal effects of beta-lactam antibiotics. Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae are all able to evade killing by penicillins, cephalosporins and carbapenems. This multi-drug resistant phenotype that challenges health care workers worldwide is caused by an array of resistance determinants. These include altered expression of outer membrane proteins and efflux pumps, along with an increasing arsenal of beta-lactamases. Future strategies in beta-lactam design must take into account the complex nature of resistance in Gram-negative pathogens.     

Epidemiology and Outcomes of Complicated Skin and Soft Tissue Infections among Inpatients in Southern China from 2008 to 2013

Complicated skin and soft tissue infections (cSSTI) are some of the most commonly treated infections in hospitals, and place heavy economic burdens on patients and society. Here we report the findings from an analysis of cSSTI based on a retrospective study which was conducted within the Chinese inpatient population. We focused our research on the analysis of the patient population, antibiotic treatment, clinical outcome and economic burden. The study population comprised 527 selected patients hospitalized between 2008 and 2013. Among the hospitalizations with microbiological diagnoses, 61.41% (n = 113) were diagnosed as infected with Gram-positive bacteria, while 46.20% (n = 85) were infected with Gram-negative bacteria. The most commonly found Gram-positive bacteria was Staphylococcus aureus (40.76%, n = 75), and the most common Gram-negative bacteria was Escherichia coli (14.13%, n = 26). About 20% of the Staphylococcus aureus were methicillin-resistant. The resistance rate of isolated Staphylococcus aureus or Escherichia coli to penicillin was around 90%; in contrast, the resistance rate to vancomycin, linezolid or imipenem was low (<20%). A large percentage of patients were treated with cephalosporins and fluoroquinolones, while vancomycin and imipenem were also included to treat drug-resistant pathogens. Over half of the hospitalizations (58.43%, n = 336) experienced treatment modifications. The cost to patients with antibiotic modifications was relatively higher than to those without. In conclusion, our study offers an analysis of the disease characteristics, microbiological diagnoses, treatment patterns and clinical outcomes of cSSTI in four hospitals in Guangdong Province, and sheds lights on the current clinical management of cSSTI in China.     

重庆地区儿童2000年至2004年首位革兰阴性细菌和阳性细菌的耐药性监测

目的了解重庆地区儿童感染的分离至临床标本的首位革兰阴性细菌和阳性细菌对常用抗生素的耐药趋势,指导临床合理使用抗生素。方法常规方法分离、培养细菌,应用美国德灵公司WalkAway-40细菌鉴定仪对2000年至2004年我院细菌室分离至临床标本的首位革兰阴性细菌和阳性细菌共2854株进行细菌鉴定及药敏试验。结果2000年至2004年检出的首位革兰阴性细菌和阳性细菌分别为大肠埃希菌和金黄色葡萄球菌。2000年至2004年前5位革兰阴性菌5777株,革兰阳性菌1565株,其中大肠埃希菌2090株,金黄色葡萄球菌764株,分别占36.2%和48.8%;5年间大肠埃希菌对氨苄西林、头孢吡肟、头孢西丁、庆大霉素、亚胺培南、环丙沙星、头孢噻肟、头孢他啶的总耐药率分别为80.9%、37.5%、15.4%、54.0%、0.8%、34.0%、46.6%、46.2%;金黄色葡萄球菌对青霉素、红霉素、复方新诺明、万古霉素、阿莫西林/克拉维酸的总耐药率分别为95.6%、63.4%、5.8%、0%、11.0%。结论通过细菌耐药监测发现：大肠埃希菌对常用抗生素的总耐药率变化不大,金黄色葡萄球菌对常用抗生素的总耐药率有下降趋势,应引起临床医生重视。     

Gram-positive merA gene in gram-negative oral and urine bacteria

Clinical mercury resistant (Hg(r)) Gram-negative bacteria carrying Gram-positive mercury reductase (merA)-like genes were characterized using DNA-DNA hybridization, PCR and sequencing. A PCR assay was developed which discriminated between the merA genes related to Staphylococcus and those related to the Bacillus/Streptococcus merA genes by the difference in size of the PCR product. DNA sequence analysis correlated with the PCR assay. The merA genes from Acinetobacter junii, Enterobacter cloacae and Escherichia coli were sequenced and shared 98-99% identical nucleotide (nt) and 99.6-100% amino acid identity with the Staphylococcus aureus MerA protein. A fourth merA gene, from Pantoeae agglomerans, was partially sequenced (60%) and had 99% identical nt and 100% amino acid identity with the Streptococcus oralis MerA protein. All the Hg(r) Gram-negative bacteria transferred their Gram-positive merA genes to a Gram-positive Enterococcus faecalis recipient with the resulting transconjugants expressing mercury resistance. These Gram-positive merA genes join Gram-positive tetracycline resistance and Gram-positive macrolide resistance genes in their association with mobile elements which are able to transfer and express in Gram-negative bacteria.     

肛周脓肿患者病原菌结构和耐药性分析

摘要 目的：分析肛周脓肿患者的病原菌结构和其耐药情况,为临床抗菌药物的选择提供依据。方法：收集医院2019年1月~2020年12月期间收治的324例肛周脓肿患者的脓液标本,在实验室进行菌株的培养、鉴定及药敏试验,记录并分析结果。结果：324例患者均送检标本共分离出病原菌516株,其中革兰阴性菌421株,占81.59%;革兰阳性菌95株,占18.41%。421株革兰阴性菌中,以大肠埃希菌的检出率最高,其次是肺炎克雷伯菌;95株革兰阳性菌中金黄色葡萄球菌检出率最高。在革兰阴性菌中,大肠埃希菌整体耐药率较高,其对氨苄西林、头孢吡肟的耐药率均超过60.00%;肺炎克雷伯菌的耐药率相对较低,仅对头孢曲松、氨苄西林的耐药率超过30.00%。在革兰阳性菌中,金黄色葡萄球菌、表皮葡萄球菌和溶血葡萄球菌对氨苄青霉素、红霉素、环丙沙星和左氧氟沙星的耐药率均较高,超过50%,同时三种葡萄球菌均未检出万古霉素和利奈唑胺的耐药菌株。结论：肛周脓肿患者的病原菌以革兰阴性菌为主,大多为大肠埃希菌和肺炎克雷伯菌,病原菌对不同抗菌药物的耐药性差异较大,应根据药敏结果合理选用抗菌药物。     

237例新生儿败血症的病原分布及耐药性分析

目的了解近年本地区新生儿败血症病原学及细菌耐药状况,用以指导临床治疗。方法对2006年5月至2010年4月收治的237例病例的血液进行培养,并对分离的菌株进行鉴定和药敏试验。结果革兰阳性菌为主要病原菌,排名前3位的病原菌分别是:表皮葡萄球菌(48.52%)、人葡萄球菌(16.03%)、凝固酶阴性葡萄球菌(10.13%)。对培养出的革兰阳性菌最敏感的抗生素是万古毒素、阿米卡星,对培养出的革兰阴性菌最敏感的抗生素是丁胺卡那霉素、亚胺培南。结论本地区新生儿血培养病原菌以革兰阳性菌为主,耐药菌株较多,临床医师应根据细菌鉴定及药敏试验选择敏感药物治疗。     

抗生素耐药基因在畜禽粪便-土壤系统中的分布、扩散及检测方法

抗生素耐药基因作为一种新型的环境污染物已引起研究者的高度关注。畜禽养殖业长期将抗生素添加到饲料中,在促进动物生长、预防和治疗动物疾病等方面起了重要作用。这些抗生素大多数不能被动物完全吸收,在动物肠道中诱导出耐抗生素细菌和抗生素耐药基因,并随着粪便排出体外。畜禽粪便作为重要的抗生素、耐抗生素细菌和抗生素耐药基因储存库,通过堆粪、施肥等农业活动进入土壤环境中,可刺激土壤中耐抗生素细菌和抗生素耐药基因的富集。耐药基因借助于基因水平转移等方式在土壤介质中进一步传播扩散,甚至进入植物中随食物链传播,对生态环境和人类健康造成极大的威胁。为了正确评估抗生素耐药基因的生态风险,本文结合国内外相关研究,系统阐述了畜禽粪便-土壤系统中抗生素耐药基因的来源、分布及扩散机制,同时探讨了细菌耐药性的主要研究方法,指出堆肥化处理仍是目前去除抗生素耐药基因的主要手段,并对今后的研究方向进行展望。     

抗生素的使用情况调查及细菌耐药性分析

目的:分析我院的抗生素的使用频率以及细菌耐药率的变化,为规范临床用药提供参考资料。方法:采用回顾性分析的方法对我院2009年3月-2013年3月收治的8000例住院患者的抗生素使用情况进行调查,并对我院临床上常见革兰阴性菌和阳性菌的耐药率变化进行比较,分析抗生素的使用频率与细菌耐药率变化之间的关系。结果:临床上抗生素的使用频率最大的是β-内酰胺酶抑制剂以及头孢菌素类。金葡菌对环丙沙星的耐药率与青霉素类抗生素的DDDs呈正相关,大肠埃希菌对亚胺培南的耐药率与头孢菌素类抗生素的DDDs呈负相关。结论:抗生素的用药频率与病原菌对抗生素的耐药率有相关性,并且,单一的抗生素并不能引起病原菌的耐药性,而会同时影响其他类型的抗生素的耐药情况。     

Bactericidal activities of essential oils of basil and sage against a range of bacteria and the effect of these essential oils on Vibrio parahaemolyticus

Basil and sage essential oils were examined for bactericidal activity against a range of Gram-positive and Gram-negative bacteria by viable count determinations. Generally, Gram-positive bacteria showed higher resistance to basil and sage essential oils than Gram-negative bacteria. Vibrio species showed a high sensitivity to both essential oils. Stationary growth phase cells of selected bacteria showed higher resistance to these essential oils than exponential growth phase cells. Basil-resistant (b21) and sage-resistant (s20) strains of Vibrio parahaemolyticus were isolated. Both strains showed higher resistance to heat and H2O2 than parent strain. Conversely, heat-adapted V. parahaemolyticus also showed a higher resistance to these essential oils than nonadapted cells.     

Guides for rational use of B-lactam antibiotics:resistance mechanism and clinical interpretation

beta-lactams are the antibiotic compounds most widely used against hospital and community acquired infections. However, resistance has emerged in both Gram-positive and Gram-negative bacteria, limiting their therapeutic efficacy. The choice of appropriate treatment depends on analysis of susceptibility data that indicates a specific mechanism of resistance. Correct interpretation of susceptibility tests permits a rational approach to the resistance problem and selection of alternatives for treatment. The laboratory must first be able to identify accurately microorganisms to the species level and then test a minimum of relevant antimicrobials. beta-lactam resistance in Enterobacteriaceae is mainly due to the production of plasmid or chromosomal encoded beta-lactamases. In Gram-negative non-fermenting bacteria, impermeability and efflux are relatively more important to the treatment selected. In Gram-positive bacteria, resistance mechanisms can involve changes in penicillin-binding proteins (PBPs), production of new PBPs or synthesis of beta-lactamases. The range of therapeutic options must be based on the current status of local resistance mechanisms.     

Ionophore resistance of ruminal bacteria and its potential impact on human health

In recent years, there has been a debate concerning the causes of antibiotic resistance and the steps that should be taken. Beef cattle in feedlots are routinely fed a class of antibiotics known as ionophores, and these compounds increase feed efficiency by as much as 10%. Some groups have argued that ionophore resistance poses the same public health threat as conventional antibiotics, but humans are not given ionophores to combat bacterial infection. Many ruminal bacteria are ionophore-resistant, but until recently the mechanism of this resistance was not well defined. Ionophores are highly lipophilic polyethers that accumulate in cell membranes and catalyze rapid ion movement. When sensitive bacteria counteract futile ion flux with membrane ATPases and transporters, they are eventually de-energized. Aerobic bacteria and mammalian enzymes can degrade ionophores, but these pathways are oxygen-dependent and not functional in anaerobic environments like the rumen or lower GI tract. Gram-positive ruminal bacteria are in many cases more sensitive to ionophores than Gram-negative species, but this model of resistance is not always clear-cut. Some Gram-negative ruminal bacteria are initially ionophore-sensitive, and even Gram-positive bacteria can adapt. Ionophore resistance appears to be mediated by extracellular polysaccharides (glycocalyx) that exclude ionophores from the cell membrane. Because cattle not receiving ionophores have large populations of resistant bacteria, it appears that this trait is due to a physiological selection rather than a mutation per se. Genes responsible for ionophore resistance in ruminal bacteria have not been identified, but there is little evidence that ionophore resistance can be spread from one bacterium to another. Given these observations, use of ionophores in animal feed is not likely to have a significant impact on the transfer of antibiotic resistance from animals to man.     

Origin, evolution, and migration of drug resistance genes

Current views on the mechanisms responsible for the emergence of multiple drug resistance in clinical bacterial isolates are considered. Hypotheses on the origin of resistance genes derived from determinants of actinomycetes, antibiotic producers, and chromosomal genes of bacteria involved in cellular metabolism are reviewed. The mechanisms underlying the diffusion of resistance determinants by means of bacterial mobile elements (plasmids, transposons, and integrons) are discussed. Examples of the horizontal transfer of resistance determinants between Gram-positive and Gram-negative bacteria are presented.     

Isopeptide bond in collagen- and fibrinogen-binding MSCRAMMs

The internal isopeptide bonds are amide bonds formed autocatalytically between the side chains of Lys and Asn/Asp residues and have been discovered recently. These bonds are well conserved in Gram-positive bacterial pilin proteins and are also observed over a wide range of Gram-positive bacterial surface proteins. The presence of these bonds confers the pilus subunits with remarkable properties in terms of thermal stability and resistance to proteases. Like pili, microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are also surface proteins found only in Gram-positive bacteria. They specifically interact with the extracellular matrix (ECM) molecules like collagen, fibrinogen, fibronectin, laminin, etc. Many biophysical and biochemical studies have been carried out to characterize the isopeptide bonds in pili proteins from Gram-positive bacteria, but no attempts have been made to study the isopeptide bonds in MSCRAMMs. This short review aims to study the significance of the isopeptide bonds in relation to their function, by analyzing the crystal structures of collagen- and fibrinogen-binding MSCRAMMs. In this analysis, interestingly, we observed that the putative isopeptide bonds are restricted to the collagen-binding MSCRAMMs. Based on analogy with bacterial pilus subunits, we hypothesize that the collagen-binding MSCRAMMs possessing putative isopeptide bonds exhibit similar structural properties, which could help the bacteria in colonizing the host and provide resistance against host–defense mechanisms.     

Marine bacteria: potential sources for compounds to overcome antibiotic resistance

Methicillin-resistant Staphylococcus aureus (MRSA) is the most problematic Gram-positive bacterium in the context of public health due to its resistance against almost all available antibiotics except vancomycin and teicoplanin. Moreover, glycopeptide-resistant S. aureus have been emerging with the increasing use of glycopeptides. Recently, resistant strains against linezolid and daptomycin, which are alternative drugs to treat MRSA infection, have also been reported. Thus, the development of new drugs or alternative therapies is clearly a matter of urgency. In response to the antibiotic resistance, many researchers have studied for alternative antibiotics and therapies. In this review, anti-MRSA substances isolated from marine bacteria, with their potential antibacterial effect against MRSA as potential anti-MRSA agents, are discussed and several strategies for overcoming the antibiotic resistance are also introduced. Our objective was to highlight marine bacteria that have potential to lead in developing novel antibiotics or clinically useful alternative therapeutic treatments.     

Origin, evolution, and migration of drug resistance genes

Current views on the mechanisms responsible for the emergence of multiple drug resistance in clinical bacterial isolates are considered. Hypotheses on the origin of resistance genes derived from determinants of actinomycetes, antibiotic-producing strains, and chromosomal genes of bacteria involved in cellular metabolism are reviewed. The mechanisms underlying the diffusion of resistance determinants by means of bacterial mobile elements (plasmids, transposons, and integrons) are discussed. Examples of the horizontal transfer of resistance determinants between Gram-positive and Gram-negative bacteria are presented.     

伤口分泌物的病原菌分布及耐药性分析

目的调查福建省龙岩市第二医院伤口分泌物病原菌的分布及耐药情况,为合理应用抗生素提供依据。方法收集2012年1月至2013年5月患者伤口分泌物标本,采用常规方法进行分离培养,用VITEK-2 Compact全自动微生物分析仪系统进行鉴定及药敏分析。结果送检503份标本,培养阳性272份,阳性率为54. 1% ;病原菌检出343株,其中革兰阴性菌189株占55. 1%,革兰阳性菌151株占44.0%,真菌3株占0.9% ;前5位的病原菌分别为金黄色葡萄球菌、凝固酶阴性葡萄球菌、铜绿假单胞菌、大肠埃希菌、鲍曼不动杆菌。耐甲氧西林金黄色葡萄球菌（MRSA）和耐甲氧西林凝固酶阴性葡萄球菌（MRCNS）的检出率分别是30.4%、82. 1%。粪肠球菌中耐高浓度氨基糖苷类肠球菌（HLAR）的检出率为55%。革兰阳性菌对万古霉素、替加环素、利奈唑胺未出现耐药菌株。铜绿假单胞菌、肠杆菌科细菌对亚胺培南的耐药率分别为5. 6%、0。大肠埃希菌中超广谱P-内酰胺酶（ESBL）的检出率是42.9%。鲍曼不动杆菌对头孢哌酮/舒巴坦的耐药率最低为25.0%,对其他抗菌药物耐药严重,多数抗菌药物的耐药率均〉45%。结论伤口感染的主要病原菌是革兰阴性菌,多重耐药菌株比例较高,临床应根据药敏结果合理选用抗生素,减少新的耐药菌株出现。