CRP regulator modulates multidrug resistance of Escherichia coli by repressing the mdtEF multidrug efflux genes

Multidrug efflux pumps contribute to the resistance of Escherichia coli against many antibiotics and biocides. Here, we report that the CRP regulator modulates multidrug resistance in E. coli through repression of the genes encoding the MdtEF multidrug efflux pump. Screening of mutants for ability to increase beta-lactam resistance in E. coli led to the identification of a mutation in crp, which codes for the major global regulator of catabolite-sensitive operons. Deletion of crp significantly increased the resistance of the E. coli strain to oxacillin, azithromycin, erythromycin and crystal violet. The increase in drug resistance caused by crp deletion was completely suppressed by deletion of the multifunctional outer membrane channel gene tolC. TolC interacts with different drug efflux pumps. Among the twenty drug efflux pumps in E. coli, quantitative real-time PCR analysis showed that CRP repressed the expression of mdtEF. Deletion of mdtEF completely suppressed CRP-modulated multidrug resistance. Therefore, in addition to its role in catabolite control, CRP contributes to multidrug resistance in E. coli. Our results indicate that the CRP regulator modulates multidrug resistance in E. coli by repressing expression of the MdtEF multidrug efflux pump.     

动物源性大肠埃希菌超广谱β-内酰胺酶的检测及耐药性研究

目的了解动物源性大肠埃希菌超广谱β-内酰胺酶（ESBLs）的检出率和耐药特点,为其耐药性的安全评价提供依据。方法采用NCCLS推荐的表型检测法和确认试验测定大肠埃希菌ESBLs,纸片扩散法测定大肠埃希菌的耐药性。结果 222株大肠埃希菌对环丙沙星（83.78%）、诺氟沙星（92.79%）、利福平（81.08%）的耐药率很高;对阿米卡星、亚胺培南高度敏感。ESBLs检出率为12.16%（27/222）,产ESBLs菌株除对亚胺培南外其余13种抗生素的耐药率均高于非产ESBLs菌株。结论动物源性大肠埃希菌对很多抗生素具有一定的耐药性,应加强对食品中动物源性大肠埃希菌耐药性的监测。     

肺炎克雷伯菌和大肠埃希菌耐药性与对多种抗菌药物使用量间的相关性分析

目的 了解严格执行抗菌药使用分级管理,控制抗菌药使用的情况下,肺炎克雷伯菌(Kp)和大肠埃希菌(E.coli)耐药的变化,探讨抗菌药使用与耐药之间的关系,为合理使用抗菌药物提供依据.方法 按季度对药敏试验结果和抗菌药使用频度(DDDS)进行统计,以Spearman相关分析法进行分析.结果 只有头孢哌酮/舒巴坦(CSL)对Kp始终保持高度敏感性,哌拉西林舒巴坦(TZP),美罗培南(IMP)和亚胺培南(MEM)耐药增长较大.对于大肠埃希菌,只有头孢他啶(CAZ),头孢吡肟(FEP)耐药呈上升趋势.头孢美唑(CMZ),头霉素类(Cephamycin),MEM以及氨基糖苷类都可影响两种细菌对其他抗菌药物的耐药率.对于Kp,CMZ DDDS与MEM,IMP,头孢噻肟(CTX),TZP高度相关(r=0.816、0.847、0.806和0.782).头霉素类DDDS与CTX、MEM和IMP中度到高度相关(r=0.585、0.673和0.815).MEM DDDS与CMZ和IMP中度相关(r＝-0.599和0.595),氨基糖苷类DDDS与MEM和CMZ的耐药率中度相关(r=0.617和0.711).对于大肠埃希菌,头霉素类、CMZ、MEM和氨基糖苷类DDDS与哌拉西林(PIP)耐药相关(r=0.722、0.721、0.634和0.606),CMZ和氨基糖苷类DDDS与CTX耐药相关(r=0.77,0.594).Kp抗菌药耐药率间相关分析发现只有环丙沙星(CIP)、SXT、CSL和FEP耐药不与其它抗菌药耐药相关,对于大肠埃希菌,只有PIP、CTX、CAZ、FEP、头孢克洛(CEC)和头孢呋辛(CXM)耐药率相互问存在相关.结论 头霉素类对其它抗菌药耐药的影响,抗菌药耐药率间相关分析可能有助于多重耐药的Kp和大肠埃希菌经验用药的选择.要控制耐药率增长,除了合理使用抗菌药,还必须控制医院感染,实行严格的隔离消毒制度.     

The impact of active and passive peer influence on young adult smoking: an experimental study

Background

Peers influence adolescent and young adult smoking, but little is known about the underlying mechanisms. It is necessary to understand whether the current assumption of peer pressure is valid, or whether an alternative explanation as imitation is more appropriate. We examined whether passive (imitation) and/or active (pressure) peer influence affects young adult smoking.

Methods

An experiment was conducted among 68 daily-smoking students aged 16–24. The actual study aim was masked. Participants had to do a 30-min music task with a confederate. The experiment consisted of a 2 (smoking condition: confederate smokes or not) by 2 (pressure condition: confederate offers the participant a cigarette or not) factorial design, resulting in four conditions: (1) no smoking and no pressure (N = 15); (2) smoking but no pressure (N = 16); (3) pressure but no smoking (N = 20); and (4) smoking and pressure (N = 17). The primary outcome tested was the total number of cigarettes smoked during this music assignment.

Results

Peer smoking significantly predicted the total number of cigarettes smoked by young adults while peer pressure did not. The interaction effect of peer pressure and peer smoking was not significant.

Conclusions

Peer pressure did not have a significant additional contribution, over and above smoking of the peer. Passive (imitation) peer influence affected young adult smoking rather than active (pressure) peer influence. Thus, smoking cessation efforts should aim at preventing interaction with smoking peers and raising awareness about its impact.     

中药逆转肿瘤多药耐药的潜力

通过对中药抗肿瘤耐药性的研究进展的探讨,综述和分析肿瘤多药耐药发生机制与逆转的药物,并对比西药来分析中药逆转肿瘤多药耐药的特征及优势,表明中药的科学性、治疗有效性、抗肿瘤作用的开发潜力很大,提出了基础研究的方向与中药逆转多药耐药的临床应用潜力与前景。     

吗丙嗪逆转多药抗药性作用及其分子机制的探讨

目的：探讨吗丙嗪逆转肿瘤多药抗药性（ＭＤＲ）的作用及其机制。方法：以ＭＴＴ与Ｆｕｒａ－２－ＡＭ法进行吗丙嗪逆转ＭＤＲ活性测定；以ＤＰＨ荧光测定法探讨吗丙嗪对膜脂流动性的影响；以荧光分光光度计法测定吗丙嗪与高钙或低钙对细胞内阿霉素（Ｄｏｘ）积累的影响及Ｆｕｒａ－２－ＡＭ法测定吗丙嗪对细胞内游离钙离子浓度的影响。结果：在浓度２．５μｍｏｌ·Ｌ－１时，吗丙嗪能显著增加ＭＣＦ－７／ＡＤＲ细胞内Ｆｕｒａ－２的积累和降低ＭＣＦ－７／ＡＤＲ对Ｄｏｘ的ＩＣ５０而对敏感株ＭＣＦ－７无明显影响，表明吗丙嗪具有逆转ＭＤＲ的作用。吗丙嗪能显著增加ＭＤＲ细胞内Ｄｏｘ积累和降低ＭＤＲ细胞的膜脂流动性。高钙或低钙对ＭＤＲ细胞内Ｄｏｘ积累无影响，吗丙嗪也不能改变１９９７－０４－１１收稿１中山医科大学中心实验室，广州５１００８９作者简介：符立梧，男，３２岁，博士，讲师，主要从事逆转多药抗药性的研究；潘启超，男，６７岁，教授，博士生导师，主要从事肿瘤药理与化疗方面的研究ＭＤＲ细胞内游离钙离子浓度。结论：吗丙嗪有逆转ＭＤＲ作用。其逆转机制与降低膜脂流动性增加细胞内ＤＯＸ积累有关，与钙离子浓度无关     

大肠埃希菌和铜绿假单胞菌的耐药性分析

目的:通过分析临床标本中大肠埃希菌和铜绿假单胞菌的分布及耐药性,了解细菌耐药性的变化趋势以及2种细菌的耐药率与抗菌药物用药频度的相关性,认识细菌耐药性变化与抗菌药物使用之间的关系。方法:调查某医院2009年至2013年临床标本中分离出的大肠埃希菌和铜绿假单胞菌,采用SPSS 17.0软件分析2种细菌耐药率与抗菌药物用药频度的相关性。结果:细菌耐药率与多种抗菌药物用药频度的关系较为复杂,但存在相关性。结论:所研究医院的大肠埃希菌及铜绿假单胞菌对于常用抗菌药物的耐药率高并与抗菌药物的用药频度有一定关系。因此,在临床工作中应严谨的使用抗菌药物以降低抗菌药物的用量,从而有效控制细菌耐药性的进展。     

大肠埃希菌临床分布及耐药性分析

目的 了解医院大肠埃希菌临床分布、标本类型、不同科室及不同年龄耐药情况,为临床合理使用抗菌药物提供依据.方法 收集亳州市人民医院2011―2018年门诊与住院病人送检10827株大肠埃希菌,回顾性分析其耐药性变化、科室分布及标本来源.结果 8年间大肠埃希菌分离率为3.92％,分离率呈下降趋势(P<0.05).共收集非重...     

致泻性大肠杆菌的流行及耐药现状

致泻性大肠杆菌(DEC)是细菌性腹泻的常见病原菌,它包括肠致病性大肠杆菌(EPEC)、产肠毒素大肠杆菌(ETEC)、侵袭性大肠杆菌(EIEC)、肠出血性大肠杆菌(EHEC)和肠聚集性大肠杆菌(EAEC)以及近来发现的肠产志贺样毒素且具侵袭力的大肠杆菌(ESIES)[1].DEC感染主要见于婴幼儿[2],近年来其在成人腹泻病人中的检出率有所增加,并成为部分地区致腹泻的主要病原菌,且对常用药物出现了较高的耐药性,因此受到了广泛的关注.     

Escherichia coli meningitis in the newborn: follow-up study.

Followup study of 22 cases of meningitis due to Escherichia coli (E. coli) in the newborn period showed a mortality rate of 7 out of 22 (31.88%), severe physical and mental sequelae occurred in one case and mild to moderate sequelae in two others. Most psychometric tests were within normal range in the survivors examined. There was a correlation between low birth weight and a high CSF protein with adverse prognosis.     

The role of OmpC and OmpF in acidic resistance in Escherichia coli

The roles of OmpC and OmpF in acidic resistance (AR) were examined. When ompC and ompF were deleted, AR was decreased. The decreased level of AR seen in the mutant that was deficient in ompC and ompF was elevated by the addition of glutamate, but not by the addition of arginine or lysine. The expression levels of adiA and cadB were diminished by the deletion of ompC and ompF, and the conversion of arginine to agmatine and lysine to cadaverine by intact cells were reduced in the mutant. The expression of gadA/gadB was not affected by the deletion of ompC and ompF. These results suggest that the transport of arginine, lysine, and their decarboxylated products through OmpC and/or OmpF is essential for the survival of Escherichia coli cells under extremely acidic conditions.     

对一株耐头孢哌酮的大肠杆菌质粒的研究

从一严重感染、经多种抗生素治疗无效而死亡病人的肺部分离到一株多重耐药物性的大肠杆菌。这株菌对头孢哌酮及其它几种抗生素高度耐药。通过对此菌进行染色体原位电泳、转化实验、限制性内切酶谱分析及ＭＩＣ值的测定．从此菌中分离出四个具有不同分子量及耐药性的质粒。其中三个质粒都对头孢哌酮表现高水平的耐药性；三个质粒对β－内酰胺类抗生素与β－内酰胺酶抑制剂的复合制剂也耐药。提示：此大肠杆菌对多种抗生素的耐药性是由质粒介导的。对其中二个质粒构建了其ＤＮＡ物理图谱。     

胶束传递系统逆转肿瘤多药耐药的研究进展

肿瘤多药耐药是目前肿瘤治疗的一大障碍。研究采用药物传递系统如胶束、脂质体、纳米粒等, 以逆转多药耐药, 显示其安全可靠, 并具有良好的应用前景。本文重点综述了药物传递系统中的聚合物胶束逆转多药耐药的研究结果及其可能的作用机制。随着研究的深入, 药物传递系统在逆转肿瘤多药耐药的研究领域将发挥更加重要的作用。     

肿瘤多药耐药逆转剂的研究进展

肿瘤细胞产生的多药耐药(multidrugresistanceMDR)已成为当前影响肿瘤化学治疗疗效的主要障碍。尽管MDR产生机制复杂,但是由mdr1基因编码的P糖蛋白(PglycoproteinPgp)的过表达是产生MDR的主要原因。寻找低毒有效的MDR逆转剂是提高化疗疗效的一个重要方法,是化疗领域亟需解决的问题。     

大肠埃希菌的临床分布及药物敏感性分析

目的了解大肠埃希菌的临床分布及其对常用抗菌药物的耐药情况,为临床抗菌药物的使用提供依据。方法应用法国生物梅里埃公司生产的API鉴定卡进行菌株鉴定,ATB药敏卡进行药敏试验,用加酶抑制剂增强试验纸片确证法进行ESBLs的确证,并对药敏结果进行分析。结果在102株大肠埃希菌中,尿液标本分离率最高（56/102）,其次是痰标本（34/102）,脓液（10/102）,胆汁和血液（各1/102）,共检出产ESBLs大肠埃希菌36株,阳性率为35%。产ESBLs大肠埃希菌对美罗培南和亚胺培南的耐药率均为0,其他抗菌药耐药率为环丙沙星94%,头孢吡肟76%,复方新诺明75%,庆大霉素67%,妥布霉素64%,乙基西梭霉素61%,阿米卡星28%,而对所有青霉素类、头孢菌素一代、二代和三代耐药率高达100%。产ESBLs菌株对抗菌药物的耐药率大部分高于不产ESBLs菌株。不产ESBLs菌株耐药率最高前三位是阿莫西林（A群青霉素）91%,替卡西林88%,头孢噻吩/1代82%;其他抗菌素（头孢西丁,头孢噻肟/3代,乙基西梭霉素,阿莫西林＋棒酸,头孢吡肟,哌拉西林＋他唑巴坦,头孢他定,阿米卡星）的耐药率均低于30%。结论大肠埃希菌产ESBLs株与非产ESBLs株对抗菌药物的耐药程度不一致,ESBLs的检测对于指导临床治疗非常重要,临床医生应根据药敏结果选择敏感性抗菌药物进行治疗。     

Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments

Fluoroquinolones are broad-spectrum antimicrobials highly effective for treatment of a variety of clinical and veterinary infections. Their antibacterial activity is due to inhibition of DNA replication. Usually resistance arises spontaneously due to point mutations that result in amino acid substitutions within the topoisomerase subunits GyrA, GyrB, ParC or ParE, decreased expression of outer membrane porins, or overexpression of multidrug efflux pumps. In addition, the recent discovery of plasmid-mediated quinolone resistance could result in horizontal transfer of fluoroquinolone resistance between strains. Acquisition of high-level resistance appears to be a multifactorial process. Care needs to taken to avoid overuse of this important class of antimicrobial in both human and veterinary medicine to prevent an increase in the occurrence of resistant zoonotic and non-zoonotic bacterial pathogens that could subsequently cause human or animal infections.     

阿霉素脂质体对克服肿瘤多药耐药的细胞学体外评价

目的:评价市售阿霉素脂质体体外逆转肿瘤多药耐药(MDR)的作用。方法:MTT法比较阿霉素和阿霉素脂质体体外对敏感和耐药细胞的细胞毒作用;荧光显微镜观察2组药物对敏感和耐药细胞的影响;流式细胞仪检测2组分别在细胞内的积累和外排情况。结果:细胞毒性试验结果显示,尽管在敏感细胞中,阿霉素脂质体IC50远高于阿霉素溶液组,对于耐药细胞株,阿霉素脂质体的IC50与游离阿霉素无显著性差异(P>0.05);细胞荧光染色显示,阿霉素脂质体较溶液在耐药细胞核中有更强的红染;细胞摄取试验显示,相同浓度下,阿霉素脂质体较溶液组在耐药细胞中积累量差异无显著性(P>0.05),但外排试验显示,在耐药细胞KBv200中,相同浓度下的脂质体较溶液具有更强的细胞滞留能力(P<0.05)。结论:阿霉素脂质体较阿霉素溶液在体外能更多进入耐药细胞核,并表现出更强的药物滞留能力,可部分克服多药耐药。