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.     

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。     

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。     

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。     

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。     

肺炎克雷伯菌毒力因子与耐药机制及其相互影响

肺炎克雷伯菌是一种革兰阴性病原体,常见于社区和医院感染,可引发肺炎、眼内炎和肝脓肿。肺炎克雷伯菌可分为经典型和高毒力型。高毒力肺炎克雷伯菌具有更多种类和数量的毒力因子,能够造成更严重的伤害。最初认为高毒力肺炎克雷伯菌对抗菌药物的治疗较为敏感,但随着抗生素时代的到来,滥用抗生素导致肺炎克雷伯菌出现了耐药性,给临床治疗带来了巨大挑战。细菌获得耐药性通常包括以下两种途径：耐药基因决定簇的水平转移和自身耐药相关基因的突变/缺失。这种获得耐药性的途径通常伴随细菌致病性的变化。本综述主要介绍肺炎克雷伯菌的毒力因子和耐药机制,并综合探讨两者之间的相互影响,为肺炎克雷伯菌的防治提供理论依据和思路。     

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     

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.     

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.     

Helicobacter pylori virulence factors as tools to study human migrations

Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA and vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.     

Gemifloxacin: effects of sub-inhibitory concentrations on various factors affecting bacterial virulence

This study investigated the ability of sub-MICs of gemifloxacin to interfere with the bacterial virulence parameters of adhesiveness, haemagglutination, hydrophobicity and motility, as well as their interactions with host neutrophilic defences such as phagocytosis, killing and respiratory bursts. The adhesiveness of both Escherichia coli and Staphylococcus aureus was significantly reduced to a subinhibitory concentration of 1/32 MIC. Indirect fimbriation parameters, such as hydrophobicity and haemagglutination were significantly reduced at a concentration of 1/8 MIC, as was migration (swarming). Phagocytosis and the respiratory burst measured by means of chemiluminescence were not affected, but killing was significantly increased from 1/2 to 1/8 MIC. The interpolation of these pharmacodynamic findings with pharmacokinetic curves indicates that sub-MIC concentrations of gemifloxacin can prolong antimicrobial effects on virulence determinants up to 27 h after the antimicrobial concentration has fallen below the MIC value.     

Effect of the herbicide 2,4-dichlorophenoxyacetic acid on uropathogenic Escherichia coli virulence factors

The effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)-widely used in the world and mainly excreted by the renal route in exposed humans-were studied on the virulence and surface characteristics of an uropathogenic Escherichia coli strain. When the urine was supplemented with 2,4-D in vitro, the compound significantly reduced the bacterial fimbriation assayed by hemagglutination and surface protein quantification. Protein values decreased from 0.24 mg/g dw to 0.05 or 0.12 mg/g dw by 1 or 0.1 mM 2,4-D treatment, respectively. The effects in vivo were studied in groups of mice challenged intra-urethra with E. coli and exposed by the oral route with three different 2,4-D doses (2.6, 25 or 70 mg/kg bw) during 22 days. Depending on the dose used, the herbicide significantly decreased or removed bacterial cells in mice bladder and kidneys; except in the group treated with the highest dose from the 9th day of treatment. The histological studies showed mononuclear cell infiltration at low doses, and toxic damage in the renal parenchyma at prolonged exposure with higher doses, up to tisular necrosis in the 70 mg/kg bw group after 9 days of treatment. Our investigations performed in an experimental model suggest that short time 2,4-D exposure at low doses could act in prevention of UTI stimulating leukocytic migration and decreasing bacterial fimbriation. On the contrary, high doses and long-term exposure enhanced renal damage resulting in infection recurrence.