multi-drug resistant

多重耐药
  • 文章类型: Journal Article
    握力(HS)充当低肌肉力量率(LMSR)的诊断标记,并反映了骨骼肌的水平。在过去的二十年里,全球数据表明,不同国家的HS呈下降趋势。
    根据最新的国家数据,2020年,中国20岁及以上成年人的平均HS记录为男性40.4kg,女性25.1kg.随着年龄的增长,HS下降,尤其是在女性中。此外,据报道,农村地区的HS值较低,而LMSR在这些地区更为普遍。
    分析中国成年人的HS和LMSR对于制定和实施旨在提高HS患病率的有针对性的干预措施至关重要。这项分析对公共卫生非常重要,有助于提高公众对LMSR的认识和促进预防措施。
    UNASSIGNED: Handgrip strength (HS) serves as a diagnostic marker for low muscle strength rate (LMSR) and reflects the level of skeletal muscle. Over the past two decades, global data indicate a downward trend in HS across various countries.
    UNASSIGNED: According to the latest national data, the mean HS among Chinese adults aged 20 years and older was recorded at 40.4 kg for males and 25.1 kg for females in 2020. A decline in HS was observed with increasing age, particularly among women. Additionally, lower HS values were reported in rural areas, whereas LMSR was more prevalent in these regions.
    UNASSIGNED: The analysis of HS and LMSR among Chinese adults is essential for the development and implementation of targeted interventions aimed at improving HS prevalence rates. This analysis is highly significant for public health, contributing to increased public awareness of LMSR and the promotion of preventative measures.
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  • 文章类型: Journal Article
    鲍曼不动杆菌,对多种药物有抗药性,是导致严重医院感染的机会性病原体。没有抗生素,噬菌体已获得临床关注。然而,由于免疫功能低下的患者通常容易感染,适当的给药时机尤为重要。在这项研究中,我们获得了特异性靶向鲍曼不动杆菌的裂解噬菌体vB_AbaM_P1。然后,我们评估了其作为临床菌株引起的肺部感染的预防性治疗的潜力。该病毒经历了持续30分钟的不活动期,并在爆发期间产生约788个颗粒。透射电镜显示vB_AbaM_P1与Saclayvirus相似。基于高通量测序和生物信息学分析,vB_AbaM_P1由107537个碱基组成,G+C含量为37.68%。它包含总共177个开放阅读框和14个tRNA。未检测到抗生素基因。体内实验,使用环磷酰胺诱导的中性粒细胞缺乏模型,通过预防性应用噬菌体,测试了噬菌体对中性粒细胞缺乏大鼠的保护作用。噬菌体的使用导致由鲍曼不动杆菌引起的大鼠死亡率的降低和肺中细菌负荷的降低。肺组织的组织学检查显示免疫细胞的存在减少。噬菌体vB_AbaM_P1的存在对预防鲍曼不动杆菌感染有显著影响,肺组织氧化应激和血清细胞因子水平的降低证明了这一点。我们的研究为早期利用噬菌体减轻鲍曼不动杆菌感染提供了更有力的证据。关键点:•从污水中分离出感染鲍曼不动杆菌的新型杆状病毒噬菌体。•确定了整个基因组,分析,与其他噬菌体相比。•测定噬菌体在嗜中性粒细胞缺陷模型中预防感染的作用。
    Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. KEY POINTS: •A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. •The whole genome was determined, analyzed, and compared to other phages. •Assaying the effect of phage in preventing infection in neutrophil-deficient models.
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  • 文章类型: Journal Article
    对多种药物(KPMDR)耐药的肺炎克雷伯菌菌株,通常在医院环境中获得并导致医疗保健相关感染,构成严重的公共卫生威胁,高毒力肺炎克雷伯菌(HvKp)也是如此,这也可能导致其他健康个体的严重感染。在最近的COVID-19大流行期间,抗生素的广泛使用往往是不必要的,这加剧了临床环境中抗生素耐药性带来的挑战。人们越来越担心高毒力(hvKp)菌株可能会获得赋予抗微生物耐药性的基因,因此,将MDR谱与它们传播到多个身体部位的能力相结合,导致难以治疗的感染。这项研究旨在比较四年(2020-2023年)收集的产KPC-3肺炎克雷伯菌分离株的耐药性和毒力谱。对所有MDRCRE-K进行基于基因组的监测肺炎用于鉴定遗传差异并表征毒力和抗性谱。我们的结果提供了抗性和毒力基因进化的图片,并有助于避免具有多药抗性和毒力增加特征的分离株的可能传播。这被认为是公共卫生面临的主要全球挑战之一,在我们的医院里。
    Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections. This study aimed to compare resistance and virulence profiles in KPC-3-producing K. pneumoniae isolates collected over four years (2020-2023). A genome-based surveillance of all MDR CRE-K. pneumoniae was used to identify genetic differences and to characterize the virulence and resistance profiles. Our results provide a picture of the evolution of resistance and virulence genes and contribute to avoiding the possible spread of isolates with characteristics of multi-drug resistance and increased virulence, which are thought to be one of the main global challenges to public health, within our hospital.
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  • 文章类型: Journal Article
    耐碳青霉烯的革兰氏阴性杆菌已经出现并在世界范围内传播。由耐碳青霉烯类分离物引起的感染由于其高发病率和死亡率而具有重大威胁。由多药耐药病原体产生的碳青霉烯酶严重限制了由对碳青霉烯类和大多数β-内酰胺抗生素均具有抗性的细菌引起的疾病的治疗选择。用于鉴定的各种表型和基因型方法可以区分不同类别的碳青霉烯酶并鉴定对碳青霉烯类具有抗性的病原体。建立一个快速的,鉴定产生碳青霉烯酶的临床菌株的准确和可靠的测试对于微生物病原体的最佳诊断和全球碳青霉烯酶产生细菌菌株流行率的管理至关重要。本文旨在总结碳青霉烯类耐药的机制,并对碳青霉烯类耐药革兰阴性杆菌的不同碳青霉烯酶检测方法进行综述。
    Gram negative bacilli that are carbapenem resistant have emerged and are spreading worldwide. Infections caused by carbapenem resistant isolates posses a significant threat due to their high morbidity and mortality rates. Carbapenemases production by multi-drug resistant pathogens severely restricts treatment choices for illnesses caused by bacteria that are resistant to both carbapenems and majority of β-lactam antibiotics. Various phenotypic and genotypic methods for identification can distinguish between different classes of carbapenemase and identify pathogens that are resistant to carbapenems. The establishment of a quick, accurate and reliable test for identifying the clinical strains that produce the carbapenemase enzyme is essential for optimum diagnosis of microbial pathogens and management of the global rise in the prevalence of carbapenemase producing bacterial strains. The aim of this review was to summarize the mechanisms of carbapenem resistance and to provide an overview of different carbapenemase detection methods for carbapenem resistant Gram negative bacilli.
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  • 文章类型: Journal Article
    鲍曼不动杆菌,机会性病原体,对重症监护病房构成重大威胁,导致严重的医院感染。多重耐药菌株的上升,特别是耐碳青霉烯的鲍曼不动杆菌,为有效治疗带来了巨大挑战。鉴于抗生素的开发周期长、费用高,噬菌体作为抵抗耐药细菌引起的感染的替代方法已经引起了临床关注。然而,噬菌体疗法的利用遇到了显著的挑战,包括窄的宿主光谱,每个噬菌体都针对有限的细菌子集,增加噬菌体抗性发展的风险。此外,治疗期间免疫系统动力学的不确定性阻碍了根据患者特定状态定制对症干预措施.在这项研究中,我们从废水中分离出两个鲍曼不动杆菌噬菌体,并对它们的潜在应用进行了全面评估。这项评估包括测序分析,基因组分类,pH和温度稳定性评估,和体外细菌抑制试验。进一步的研究涉及分析接受噬菌体鸡尾酒治疗肺炎的大鼠的组织学和细胞因子变化。噬菌体的治疗效果得到验证,在噬菌体治疗期间,大鼠肺组织的转录组学研究揭示了免疫系统的重要变化。我们的研究结果强调了噬菌体作为治疗策略的未来发展的潜力,并提供了有关整个治疗过程中免疫系统动力学的令人信服的证据。重要性由于多重耐药细菌的问题日益严重,噬菌体的使用被认为是抗生素的替代品,噬菌体的遗传安全性和应用稳定性决定了噬菌体应用的潜力。噬菌体基因组中不存在耐药基因和毒力基因,可以保证噬菌体应用的安全性,噬菌体可以在很宽的温度和pH范围内保持活性的事实也是应用所必需的。此外,临床前研究的效果评价对临床应用尤为重要。通过哺乳动物模型模拟治疗过程中的免疫反应情况,可以观察到动物免疫力的变化,和噬菌体疗法的效果可以进一步评估。我们的研究提供了令人信服的证据,表明噬菌体有望进一步发展为鲍曼不动杆菌感染的治疗剂。
    Acinetobacter baumannii, an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant A. baumannii, has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two A. baumannii phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and in vitro bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study underscore the potential of phages for future development as a treatment strategy and offer compelling evidence regarding immune system dynamics throughout the treatment process.IMPORTANCEDue to the growing problem of multi-drug-resistant bacteria, the use of phages is being considered as an alternative to antibiotics, and the genetic safety and application stability of phages determine the potential of phage application. The absence of drug resistance genes and virulence genes in the phage genome can ensure the safety of phage application, and the fact that phage can remain active in a wide range of temperatures and pH is also necessary for application. In addition, the effect evaluation of preclinical studies is especially important for clinical application. By simulating the immune response situation during the treatment process through mammalian models, the changes in animal immunity can be observed, and the effect of phage therapy can be further evaluated. Our study provides compelling evidence that phages hold promise for further development as therapeutic agents for Acinetobacter baumannii infections.
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  • 文章类型: Journal Article
    食源性感染仍然是国际一级的主要公共卫生问题。在埃塞俄比亚等发展中国家,这个问题变得更加严重。
    本研究旨在研究沙门氏菌和志贺氏菌和肠道寄生虫的流行情况。以及埃塞俄比亚西北部冈达尔大学自助餐厅的食品处理人员对抗生素的耐药性模式和相关因素。
    一项基于机构的横断面研究于2021年2月至6月在冈达大学自助餐厅进行。使用结构化问卷收集与研究参与者的社会人口统计学特征和卫生习惯相关的数据。从食品处理人员收集了总共290个粪便样品。使用培养和常规生化测试来分离沙门氏菌和志贺氏菌。湿支架,甲酸醚浓度,和KatoKatz技术用于鉴定肠道寄生虫。此外,使用纸片扩散法进行药物敏感性试验.使用SPSS版本26进行统计分析。
    分析了290名食品处理人员的粪便样本,27例(9.3%)沙门氏菌和志贺氏菌均呈阳性。沙门氏菌和志贺氏菌的流行率分别为16种(5.5%)和11种(3.8%),分别。大多数分离的病原菌对四环素19耐药(70.4%),甲氧苄啶/磺胺甲恶唑19(70.4%)。耐多药志贺氏菌和沙门菌的总检出率为59.3%。此外,57(19.7%)的参与者对一种或多种肠道寄生虫呈阳性。最普遍的肠道寄生虫病是溶组织大肠杆菌/dispar22(7.6%),其次是G.Lamblia13(4.5%),和A虫11(3.8)使用厕所后不洗手(AOR:4.42,95%CI:1.57,10.56),和食用未经巴氏灭菌的牛奶(AOR:3.14,95%CI:1.65,3.96),是与沙门氏菌患病率显着相关的因素,和志贺氏菌感染。同样,上厕所后不洗手(AOR:2.19,95%CI:1.0,1.4),和食用未经巴氏灭菌的牛奶(AOR:10.4,95%CI:3.8,28.8),是与肠道寄生虫感染患病率显著相关的因素。
    肠道寄生虫的患病率,沙门氏菌,志贺氏菌种类很高。因此,必须实施一项包括持续微生物监测的公共卫生政策。
    Food-borne infections continue to be a major public health problem at the international level. The issue becomes more serious in developing countries like Ethiopia.
    This study aimed to examine the prevalence of Salmonella and Shigella species and intestinal parasites, as well as antimicrobial resistance patterns and associated factors among food handlers at the University of Gondar cafeteria in northwest Ethiopia.
    An institutional-based cross-sectional study was conducted from February to June 2021 in the University of Gondar cafeterias. Data related to the socio-demographic characteristics and hygienic practices of study participants were collected using structured questionnaires. A total of 290 stool samples were collected from food handlers. Culture and conventional biochemical tests were used to isolate the Salmonella and the Shigella species. Wet mount, Formol-ether concentration, and Kato Katz techniques were applied to identify intestinal parasites. Additionally, drug susceptibility tests were performed using the disk diffusion method. Statistical analysis was done using SPSS version 26.
    Of 290 food handlers\' stool samples analyzed, Twenty-seven 27 (9.3%) were positive for both Salmonella and Shigella species. The prevalence of Salmonella and Shigella species was 16 (5.5%) and 11 (3.8%), respectively. Most of the isolated pathogens were resistant to tetracycline 19 (70.4%), and trimethoprim/sulphamethoxazole 19 (70.4%). The overall rate of multi-drug resistant Shigella and Salmonella isolate was 59.3%. Besides, Fifty-seven 57 (19.7%) of the participants were positive for one or more intestinal parasites. The most prevalent intestinal Parasitosis was E. histolytica/dispar 22 (7.6%), followed by G. lamblia 13 (4.5%), and Ascaris lumbricoides 11 (3.8) not washing hands after using the toilet (AOR: 4.42, 95% CI: 1.57, 10.56), and consuming unpasteurized milk (AOR: 3.14, 95% CI: 1.65, 3.96), were factors significantly associated with the prevalence of Salmonella, and Shigella infection. Similarly, not washing hands after using the toilet (AOR: 2.19, 95% CI: 1.0, 1.4), and consuming unpasteurized milk (AOR: 10.4, 95% CI: 3.8, 28.8), were factors significantly associated with the prevalence of intestinal parasites infection.
    The prevalence of intestinal parasites, Salmonella, and Shigella species was high. Therefore, it is imperative to implement a public health policy that includes ongoing microbiological surveillance.
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  • 文章类型: Journal Article
    鲍曼不动杆菌是土壤和水中常见的革兰氏阴性菌。尽管被认为是人体皮肤菌群的典型组成部分,它已经成为一种重要的机会病原体,尤其是在医疗机构。鲍曼不动杆菌的致病性归因于其毒力因子,其中包括粘附素,pili,脂多糖,外膜蛋白,铁吸收系统,自动运输,分泌系统,磷脂酶等.这些元素为细菌提供了粘附和穿透宿主细胞的能力,通过宿主免疫系统,并破坏组织。它的感染是导致包括肺炎在内的人类病理生理疾病的主要因素,血流感染,尿路感染,和手术部位感染。治疗由这种病原体引起的感染是具有挑战性的,因为这种细菌已经进化为耐受多种药物,并且耐药性鲍曼不动杆菌的进一步出现导致更高的发病率和死亡率。这种细菌在医疗用品和医院家具表面上的长期存活促进了它在人类中从一个栖息地到另一个栖息地的频繁传播。需要进行紧急研究以找到鲍曼不动杆菌的有效药物靶标以及设计减少感染的存活和传播的新药。在当前的审查中,我们代表特定的特征,发病机制,以及鲍曼不动杆菌关键药物靶标的分子复杂性。这也将有助于提出预防和治疗鲍曼不动杆菌感染及其传播的策略和替代疗法。
    Acinetobacter baumannii is observed as a common species of Gram-negative bacteria that exist in soil and water. Despite being accepted as a typical component of human skin flora, it has become an important opportunistic pathogen, especially in healthcare settings. The pathogenicity of A. baumannii is attributed to its virulence factors, which include adhesins, pili, lipopolysaccharides, outer membrane proteins, iron uptake systems, autotransporter, secretion systems, phospholipases etc. These elements provide the bacterium the ability to cling to and penetrate host cells, get past the host immune system, and destroy tissue. Its infection is a major contributor to human pathophysiological conditions including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections. It is challenging to treat infections brought on by this pathogen since this bacterium has evolved to withstand numerous drugs and further emergence of drug-resistant A. baumannii results in higher rates of morbidity and mortality. The long-term survival of this bacterium on surfaces of medical supplies and hospital furniture facilitates its frequent spread in humans from one habitat to another. There is a need for urgent investigations to find effective drug targets for A. baumannii as well as designing novel drugs to reduce the survival and spread of infection. In the current review, we represent the specific features, pathogenesis, and molecular intricacies of crucial drug targets of A. baumannii. This would also assist in proposing strategies and alternative therapies for the prevention and treatment of A. baumannii infections and their spread.
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  • 文章类型: Journal Article
    根据世界卫生组织,传染病,特别是由多重耐药细菌(MDR)引起的,预计到2050年将夺走1500万人的生命。败血症的发病率和死亡率高于易感铜绿假单胞菌。MDR介导的眼部感染可导致视力受损和失明。确定和开发一种潜在的抗MDR铜绿假单胞菌的药物,我们从事基于硅反向遗传学的目标挖掘,药物优先,和评价。选择稀有脂蛋白A(RlpA)作为靶蛋白,并对其晶体结构进行了几何优化。分子对接和虚拟筛选分析表明,RlpA与11种化合物具有很强的结合亲和力。其中,对3-氯邻苯二甲酸进行了评估,和随后的体外试验证明了显著的抗假单胞菌活性,具有可忽略的细胞毒性。该化合物在体外对药物敏感和MDR铜绿假单胞菌菌株进行了进一步评估,使用MTT测定法评估细胞毒性。研究表明,3-氯邻苯二甲酸具有有效的抗假单胞菌活性,对宿主细胞的毒性最小。因此,这种化合物是一种有希望的候选抗MDR铜绿假单胞菌,保证进一步调查。
    According to the World Health Organization, infectious diseases, particularly those caused by multidrug-resistant bacteria (MDR), are projected to claim the lives of 15 million people by 2050. Septicemia carries a higher morbidity and mortality rate than infections caused by susceptible Pseudomonas aeruginosa, and MDR-mediated ocular infections can lead to impaired vision and blindness. To identify and develop a potential drug against MDR P. aeruginosa, we employed in silico reverse genetics-based target mining, drug prioritization, and evaluation. Rare Lipoprotein A (RlpA) was selected as the target protein, and its crystal structure was geometrically optimized. Molecular docking and virtual screening analyses revealed that RlpA exhibits strong binding affinity with 11 compounds. Among these, 3-chlorophthalic acid was evaluated, and subsequent in vitro assays demonstrated significant anti-Pseudomonas activity with negligible cytotoxicity. The compound was further evaluated against both drug-susceptible and MDR P. aeruginosa strains in vitro, with cytotoxicity assessed using an MTT assay. The study demonstrated that 3-chlorophthalic acid exhibits potent anti-Pseudomonas activity with minimal toxicity to host cells. Consequently, this compound emerges as a promising candidate against MDR P. aeruginosa, warranting further investigation.
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  • 文章类型: Journal Article
    鲍曼不动杆菌中pgaB相关的生物膜形成增强了毒力,同时具有高度的耐药性倾向。因此,这项研究旨在对pgaB基因进行分子表征,并检查其与MDR的共存。选择
    鲍曼不动杆菌(N=73)的MDR菌株来检测生物膜的形成。进一步提取基因组DNA并筛选pgaB,然后从代表性菌株进行扩增子测序。进一步检查其在不同耐药菌株组中的显著p值<0.05的分布频率。
    生物膜测定显示高,低生物膜和负生物膜形成率为58.9%,分别为31.5%和0.9%的菌株。在14株MDR鲍曼不动杆菌中检测到pgaB基因(19.17%)。pgaB基因的同时出现在所有对β-内酰胺抑制剂具有抗性的菌株中,头孢,碳青霉烯类,氟喹诺酮类和叶酸类其次是96%的氨基糖苷类和25%的外排泵组。
    研究结果表明,在MDR鲍曼不动杆菌菌株中存在与pgaB相关的生物膜。结果还建议通过进一步的实验来追踪其在改变耐药性模式中的作用。
    UNASSIGNED: pgaB associated biofilm formation in Acinetobacter baumannii enhances the virulence in concert with the high propensity of drug resistance. This research is thus aimed to characterize the pgaB gene molecularly and to examine its co-occurrence with MDR.
    UNASSIGNED: MDR strains of A. baumannii (N = 73) were selected to detect the formation of biofilms. Genomic DNA was extracted further and screened for pgaB followed by amplicon sequencing from the representative strains. Frequency of its distribution in different groups of drug resistant strains at a significant p-value of <0.05 was further checked.
    UNASSIGNED: The biofilm assay showed high, low and negative biofilm formers in 58.9%, 31.5% and 0.9% of the strains respectively. The pgaB gene was detected in 14 strains of MDR A. baumannii (19.17%). Co-occurrence of pgaB gene was seen in all the strains that showed resistance to β-lactam inhibitors, cephems, carbapenems, fluoroquinolones and folates followed by 96% for the aminoglycosides and 25% in the efflux pump groups.
    UNASSIGNED: The study findings showed the occurrence of biofilms associated with pgaB in MDR A. baumannii strains. The results also suggest to track its role in varying the pattern of drug resistance with further experimentation.
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  • 文章类型: Journal Article
    虽然转译系统是一个很有前途的目标,用于抗菌的发展,其在肺炎克雷伯菌(KP)中的抗菌机制尚不清楚。考虑到tmRNA是转译的核心组成部分,本研究首先调查了缺乏转译活性(tmRNA缺失)的KP中各种环境压力引起的表型变化,然后旨在根据氨基糖苷类抗生素对转译的抑制活性,评估转译靶向抗生素组合(妥布霉素/环丙沙星)在临床KP分离株中的抗菌活性。我们发现,在高渗性(0.5和1MNaCl)的环境下,tmRNA缺失的菌株P4325/ΔssrA比野生型KP菌株P4325明显更易感,过氧化氢(40mM),和紫外线照射。在P4325/ΔssrA和P4325之间没有观察到在人血清下的生物膜形成和存活的显着差异。tmRNA缺失导致氨基糖苷类的MIC值降低两倍。至于膜的通透性,在存在或不存在维拉帕米和羰基氰-间氯苯腙(CCCP)的情况下,tmRNA缺失增加了KP的溴化乙锭(EtBr)摄取,在P4325/ΔssrA中利血平存在下,EtBr吸收降低,并在CCCP存在下减少了P4325/ΔssrA中的EtBr流出。时间杀死曲线和体外实验显示,靶向tmRNA的基于氨基糖苷的抗生素组合(妥布霉素/环丙沙星)具有显着的杀菌活性。因此,相应的tmRNA靶向抗生素组合(基于氨基糖苷)可能是对抗多药耐药KP的有效且有前景的治疗选择.
    Although the trans-translation system is a promising target for antcibiotic development, its antibacterial mechanism in Klebsiella pneumoniae (KP) is unclear. Considering that tmRNA was the core component of trans-translation, this study firstly investigated phenotypic changes caused by various environmental stresses in KP lacking trans-translation activities (tmRNA-deleted), and then aimed to evaluate antibacterial activities of the trans-translation-targeting antibiotic combination (tobramycin/ciprofloxacin) in clinical KP isolates based on inhibition activities of aminoglycosides against trans-translation. We found that the tmRNA-deleted strain P4325/ΔssrA was significantly more susceptible than the wild-type KP strain P4325 under environments with hypertonicity (0.5 and 1 M NaCl), hydrogen peroxide (40 mM), and UV irradiation. No significant differences in biofilm formation and survivals under human serum were observed between P4325/ΔssrA and P4325. tmRNA deletion caused twofold lower MIC values for aminoglycosides. As for the membrane permeability, tmRNA deletion increased ethidium bromide (EtBr) uptake of KP in the presence or absence of verapamil and carbonyl cyanide-m-chlorophenylhydrazone (CCCP), decreased EtBr uptake in presence of reserpine in P4325/ΔssrA, and reduced EtBr efflux in P4325/ΔssrA in the presence of CCCP. The time-kill curve and in vitro experiments revealed significant bactericidal activities of the tmRNA-targeting aminoglycoside-based antibiotic combination (tobramycin/ciprofloxacin). Thus, the corresponding tmRNA-targeting antibiotic combinations (aminoglycoside-based) might be effective and promising treatment options against multi-drug resistant KP.
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