布伦登卢普沙门菌耐药性与毒力基因分析

目的 研究临床分离的非伤寒沙门菌布伦登卢普血清型（布伦登卢普沙门菌）对抗菌药物的耐药性及其 携带的毒力基因特征。方法 收集 2012—2014 年每年 4—10 月天津市两家教学医院肠道门诊急性腹泻患者的临 床资料, 将急性腹泻患者粪便标本进行沙门菌分离培养、 生化及 PCR 鉴定、 血清学分型, 对得到的布伦登卢普沙门菌 进行抗菌药物敏感性检测、 PCR 扩增沙门菌毒力岛 （SPI） 1~5 的代表性基因和 SPI 的调节基因。结果 3 年共检测到 非重复非伤寒沙门菌 153 株, 其中 8 株 （5.23%） 为布伦登卢普沙门菌。8 株 invA-PCR 鉴定均呈阳性, 对萘啶酸耐药 率 100%, 对环丙沙星和左氧氟沙星中介耐药率 100%, 对其余检测的抗菌药物敏感; 8 株均检测到了 SPI 1~5 代表性 基因和 SPI 调节基因 （sitC、 hilA、 sseL、 sifA、 mgtC、 siiE、 sopB 和 phoP）。结论 天津地区布伦登卢普沙门菌临床株对氟 喹诺酮耐药并携带 SPI 1~5 毒力基因与调节基因, 对公众健康构成潜在威胁, 应持续开展相关监测与研究。     

高毒力肺炎克雷伯菌临床感染特征及毒力因子研究进展

肺炎克雷伯菌是常见的革兰阴性机会致病菌,引发多种感染疾病。而高毒力肺炎克雷伯菌的出现不仅在健康人群中传播致病,并且伴有感染扩散转移、损伤中枢神经等危害。其主要毒力因子包括荚膜多糖、可移动遗传元件、调控基因、铁载体等。且由于可移动遗传因子的传播导致高毒力肺炎克雷伯菌已经出现了与耐药性的协同,严重危害公共安全卫生。因此本文对其临床感染特征、毒力因子、与耐药性的协同进行综述,以便为后续的研究提供参考。     

沙门菌CWDMs细胞结构的研究

目的 了解沙门菌ＣＷＤＭｓ的形态、细胞超微结构以及细胞壁和胞浆膜的化学结构,探讨沙门菌ＣＷＤＭｓ变异的性质及其机制。方法 采用电子显微镜观察及抗生素、溶菌酶、毛垢黄皂苷敏感试验等方法。结果 伤寒杆菌和甲型事伤寒杆菌的ＣＷＤＭｓ均为产生红色色素、直径０．６～１．２μｍ的感试验等方法。结果 伤寒杆菌和甲型副伤寒杆菌的ＣＷＤＭｓ均为科生红色色素、直径０．６～１．２ｕｍ的革兰氏阴性圆球形态,单个或２～４个     

用减毒沙门菌菌苗控制幽门螺杆菌相关疾病

用幽门螺杆菌 ( Hp)抗原加佐剂或用减毒沙门菌传递抗原的新免疫接种策略能成功地保护小鼠免受 Hp感染。口服 1剂表达脲酶的减毒沙门菌菌苗能诱导粘膜和全身抗体应答 ,并能完全保护不同品系小鼠免受 Hp感染。这种高效、高免疫原性、安全且低成本的菌苗是预防人类 Hp相关疾病有希望的候选菌苗     

一起沙门菌引起食物中毒的调查分析

2000年7月4日,周宁县泗桥乡赤岩村发生一起食物中毒,就餐村民186人,中毒46人,调查证实本次食物中毒系由沙门菌污染食物所致。现将调查结果报告如下。     

重组沙门菌疫苗研究进展

沙门菌是人兽共患病病原,研究其重组减毒疫苗在医学、兽医学和公共卫生学领域均具有重要意义。同时以重组减毒沙门菌为载体还可以进一步构建适用于病毒、细菌、寄生虫、肿瘤治疗的基因工程疫苗和基因疫苗,这些疫苗具有良好的稳定性和免疫原性,展示了良好的应用前景。本文对相关研究进展进行综述。     

用减毒沙门菌菌苗控制幽门螺杆菌相关疾病

用幽门螺杆菌（Ｈｐ）抗原加佐剂或用减毒沙门菌传递抗原的新免疫接种策略能成功地保护小鼠免受Ｈｐ感染。口服１剂表达脲酶的减毒沙门菌菌苗能诱导粘膜和全身抗体应答,并能完全保护不同品系小鼠免受Ｈｐ感染。这种高效、高免疫原性、安全且低成本的菌苗是预防人类Ｈｐ相关疾病有希望的候选菌苗。     

儿童沙门菌感染44例流行病学特征和耐药分析

目的了解近年本地区儿童沙门菌感染的流行病学特征和耐药性。方法回顾分析本院微生物室2008～2012年从儿科分离到的临床确诊为沙门菌感染的沙门菌株及临床资料。结果44株沙门菌主要分离自〈1岁婴幼儿（占59．09％）。共分8种血清型,鼠伤寒沙门菌为主要血清型（占65．91％）。鼠伤寒沙门菌对亚胺培南、头孢他啶、头孢曲松、头孢噻肟敏感率分别为100．00％、100．00％、96．56％、96．56％;对氨苄西林,复方新诺明、哌拉西林、环丙沙星敏感率分别24．14％、41．38％、41．38％、55．17％。结论本地区儿童沙门菌感染以婴幼儿鼠伤寒沙门菌感染为主。鼠伤寒沙门菌对亚胺培南、三代头孢菌素敏感率高,对氨苄西林、复方新诺明、哌拉西林、环丙沙星敏感率低。     

Class 1 integrons and virulence genes in Salmonella enterica isolates from pork and humans

In this study, 183 Salmonella enterica isolates were characterised for integrons and virulence genes. Among the isolates, 46% were positive for intI1, but no isolates carried intI2 or intI3. Eighteen class 1 integrons (21%) contained resistance gene cassettes (i.e. dfrA1-orfC, dfrA12-aadA2, bla(PSE-1) and aadA2) and five class 1 integrons with the dfrA12-aadA2 array were conjugally transferable. Two Salmonella pork isolates of serotypes Albany and Kedougou possessed Salmonella genomic island 1 variants SGI1-G and SGI1-F, respectively. Four class 1 integrons contained an atypical 3'-CS linked to the qacH-sul3 domain, and three were not a sul type. Two novel GyrA mutations (Pro-45→Ser and Met-48→Ile) and three novel ParC mutations (Ser-5→Arg, Thr-31→Met and Leu-77→Arg) were identified in ciprofloxacin-resistant isolates. At least 90% of the Salmonella isolates contained pagC, prgH, sitC, sipB or spaN, whereas all isolates harboured invA, msgA, spiA and tolC.     

Targeting virulence for antibacterial chemotherapy: identifying and characterising virulence factors for lead discovery

The antibacterial drug discovery industry is fast losing participants; at the same time it is facing the challenge of developing new antibiotics that are effective against frequently occurring and multiply resistant organisms. One intriguing approach is to target bacterial virulence, and the last decade or so has seen a focus on bacterial pathogenesis along with the development of reagents and strategies that could make this possible. Several processes utilised by a range of bacteria to cause infection may be conserved enough to make attractive targets; indeed it is known that mammalian cells can affect bacterial gene expression and vice versa. Interesting targets involving virulence include type III secretion systems, two-component signal transduction systems, quorum sensing, and biofilm formation. In order to better understand these systems and strategies, investigators have developed novel strategies of their own, involving negative selections, surrogate models of infection, and screens for gene induction and antigenicity. Inhibitors of such targets would be unlikely to adversely affect patients, be cross-resistant to existing therapies, or cause resistance themselves. It might be the case that virulence target-based therapies would not be powerful enough to clear an existing infection alone, but if they are instead considered as adjunct therapy to existing antibiotics, or potentiators of the host immune response, they may show efficacy in a non-traditional way.     

幽门螺杆菌致病因子与胃黏膜屏障

<正>1正常胃及十二指肠黏膜屏障的保护作用早在1954年Hollander提出双层黏障学说,“双障”是指黏液屏障和黏膜屏障,它可使黏膜上皮免遭机械损伤和各种化学刺激,并可中和胃酸和     

革兰阴性病原菌毒力因子及抗毒力治疗策略进展

由于致病菌耐药性的不断增长,传统抗菌药物的效力普遍下降,因而开发新颖的抗感染药物和抗菌疗法迫在眉睫。侧重于对抗细菌毒力因子的抗毒力治疗已成为一种新的治疗策略。与传统抗生素治疗不同,抗毒力治疗只是剥夺病原菌的毒力而不抑制它们生长或杀死病原菌。为了更好的开发抗毒力治疗这一新型抗菌疗法,对毒力因子的认识还需加强。本文主要就革兰阴性病原菌的攻击性毒力因子、防御性毒力因子、毒力因子表达受到的调控以及抗毒力治疗策略相关的研究进行了综述,以期为研究新颖有效的抗菌疗法,缓解致病菌感染及耐药现状提供新视角。     

化脓性链球菌耐药与毒力基因研究

目的 调查一组70株化脓性链球菌耐药与毒力基因存在状况，以及菌株间的亲缘关系。方法 70株化脓性链球菌分离自日照市中心医院2012-2017年急性扁桃体炎、急性咽炎患者的咽拭子标本。5种抗菌药物敏感性试验为Kirby-Bauer法。采用聚合酶链反应(PCR)及序列分析的方法分析8种耐药基因和3种毒力基因。检测结果作样本聚类分析(UPGMA法)。结果 70株化脓性链球菌对青霉素、苯唑西林、万古霉素敏感性均达100.00%，对红霉素耐药率较高(94.29%)。青霉素耐药基因均为阴性，大环内酯类耐药基因检出ermB和mefA基因，其中ermB和/或mefA阳性66株(94.29%)。可移动遗传元件标志基因intTN916检出率高(94.29%)。3种毒力基因均有较高的检出率：spyA58株(82.86%)、sagA68株(97.14%)、slo64株(91.43%)。样本聚类分析可见，70株化脓性链球菌分为A~N共14个分类单元，根据是否携带ermB基因，可分为Ⅰ、Ⅱ二个群，Ⅰ群9个分类单元均携带ermB基因，Ⅱ群5个分类单元均不携带ermB基因。结论 70株化脓性链球菌携带的大环内酯类耐药基因ermB和mefA，以及可移动遗传元件标志基因intTN916是对红霉素产生耐药的重要原因。spyA、sagA、slo等3种毒力基因是化脓性链球菌常见的毒力基因,推测它们是化脓性链球菌感染导致感染灶局部炎症和坏死的原因。     

幽门螺杆菌细胞毒导致胃癌发生的作用机制

幽门螺杆菌(Helicobacter pylori,Hp)感染导致胃癌的重要原因之一是它的细胞毒作用。细胞毒素相关基因致病岛(cytotoxin-associated gene pathogenicity island,cagPAI)和空泡毒素A(vacuolatingcytotoxin A,vacA)是Hp最典型的细胞毒代表。cagPAI可诱发促炎因子的释放及增强促上皮细胞增殖信号的兴奋程度;vacA则导致上皮空泡化和病原体黏附。明确cagPAI和vacA在胃癌发生发展过程中的作用,将有利于全面理解Hp感染对机体造成的危害以及根治Hp感染的重要意义。     

Small-molecular virulence inhibitors show divergent and immunomodulatory effects in infection models of Salmonella enterica serovar Typhimurium

The virulence-associated Salmonella pathogenicity island 2 (SPI2) type III secretion system supports intracellular replication of Salmonella enterica serovar Typhimurium in macrophage-like RAW264.7 cells. In contrast, the salicylidene acylhydrazide INP0010 and the benzimidazole omeprazole prevent virulence factor-mediated replication of S. Typhimurium in these cells. Here we show that INP0010 enhances expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) production, the oxidative burst and tumour necrosis factor-alpha (TNFα) release in infected RAW264.7 cells. INP0010 also inhibited SPI2 activity in RAW264.7 cells. The ability of INP0010 to suppress bacterial intracellular replication correlated with NO production. The iNOS inhibitor N-monomethyl-l-arginine restored SPI2 activity and antagonised the bacteriostatic effect of INP0010. Omeprazole, which inhibited iNOS expression in RAW264.7 cells, likewise antagonised INP0010. In infected epithelioid MDCK cells that did not express NO upon infection, INP0010 enhanced bacterial intracellular replication. In Caenorhabditis elegans, INP0010 significantly attenuated the virulence of S. Typhimurium. In this infection model, the attenuating effect of INP0010 was further enhanced by omeprazole. These results demonstrate that chemically unrelated virulence inhibitors may act in an antagonistic or additive manner, that their effect depends on the infection model applied, and that the attenuating effects of INP0010 in part relate to its ability to promote the SPI2 antagonist NO.     

Relationship between susceptibility to antimicrobials and virulence factors in paediatric Escherichia coli isolates

The in vitro susceptibilities to several antibiotics of 136 Escherichia coli strains containing virulence factors isolated from children with urinary tract infection were analysed. Escherichia coli strains were analysed by multiplex polymerase chain reaction for genes encoding the following virulence factors: pyelonephritis-associated pili (pap); S fimbriae (sfa); afimbrial adhesin I (afaI); haemolysin (hly); cytotoxic necrotizing factor I (cnfI); and aerobactin (aer). It was observed that the virulence genes increased antibiotic resistance of resistant strains and increased the sensitivity of susceptible strains.