志贺菌属致病的研究进展

致病岛是指细菌染色体上具有典型结构特征的基因片段,主要编码细菌毒力及代谢相关产物。志贺菌属基因组中已发现了多个致病岛,并广泛存在于该菌属的各群细菌中,与致病性和耐药性等密切相关。对志贺菌属致病岛的研究为进一步深入理解其致病机制、开发防治细菌性痢疾的新策略提供了理论依据。     

致病菌基因组岛的研究进展

细菌基因组岛是细菌基因组上的特定区域,和水平基因转移相关,具有一定的结构特点,常携带致病、耐药及与适应性等功能相关的基因。通过基因组岛在细菌间的移动,可以造成相关基因在细菌间的传播,在细菌生存和致病等过程中具有重要作用。目前已经可通过生物信息和分子生物学实验等方法对基因组岛进行预测和验证。通过对致病菌基因组岛的研究,可以阐释细菌致病性和耐药等重要功能的获得,对疾病进行溯源,在传染病预防控制中具有重要意义。     

猪链球菌2型89K毒力岛研究进展

高致病性猪链球菌2型的致病机制仍是未解之谜.毒力岛不仅赋予病原菌特殊的致病能力,而且在细菌的适应性进化过程中扮演重要角色.对猪链球菌2型89K毒力岛功能性基因的深入剖析有助于更全面地掌握病原菌的致病特性.综述了猪链球菌2型89K毒力岛的结构与进化过程,以及国内外对毒力岛中二元信号转导系统、Ⅳ型分泌系统、ABC转运蛋白、毒素-抗毒素系统等重要基因的研究进展,力图从基因水平为猪链球菌2型的致病机制寻找突破口.     

013 幽门螺杆菌基因组可塑性区中新的致病性基因

幽门螺杆菌(Hp)为革兰阴性、螺旋形的微需氧杆菌,它在慢性胃炎、消化性溃疡、胃肿瘤的致病中发挥重要作用,但不同菌株的致病性不尽相同。细胞毒素相关基因(cagA)是第1个被发现的存在于致病岛(cagA PAI)的毒性基因;而存于cag PAI外,但与cag PAI特点相似的基因区,可能是潜在的致病     

细菌性腹泻病原菌及体外遗传工程

<正>微生物遗传和DNA生物化学新近的发展,促进了微生物致病性物质的分子遗传学研究,其中以致病性大肠杆菌和霍乱弧菌研究进展较快。应用这些技术研究微生物致病性遗传因子的结构和功能,对致病机制可得到更多的了解,这样,对传染病的预防免疫及某些传染病的抗生素治疗会有所帮助。 按经典的遗传学方法来分离及研究无毒     

鸡源沙门氏菌(Salmonella)致病基因与致病性的相关性研究

为分析沙门氏菌分离株致病基因与致病性之间的关系,采集经分离鉴定的55株鸡源沙门氏菌,应用PCR方法检测毒力基因,通过小鼠致病试验检测致病性。结果显示,所检测的质粒毒力基因spvR、spvA、spvB、spvC、spvD,检出率均在60%以上;所检测的毒力岛毒力基因invH、sipA、sipB、sopA、sopD、avrA、hilA、iacP、prgK、ssaB、ssaQ、sifA、sseL、ssrA、ttrB、mgtC、misL、rmbA、rhuM、sugR、orf319、siiD、siiE、spi4H、sopB和pipC中,ttrB检出率最高,为92.73%,sifA检出率最低,为5.45%。55株分离株对小鼠均具有致病性,致死率为20%～100%;随机测定其中10株的半数致死量(LD_(50)),为4×10~7～3.18×10~8CFU/mL,毒力基因检出数量越多的分离株,其LD_(50)值越小,毒力越强。本研究结果揭示,鸡源致病性沙门氏菌分离株普遍携带毒力基因,其毒力基因与致病性之间呈现正相关,为深入研究沙门氏菌的致病机理提供基础数据。     

鼠伤寒沙门菌的致病基因

在鼠伤寒沙门菌（鼠伤寒杆菌ＳＴＭ）与宿主相互作用过程中,有众多的致病基因参与。这些基因少数位于毒力相关的大质粒上,绝大多数位于染色体上的病力岛目前已发现了３种毒力岛（ＳＰＩ－１,ＳＰＩ－２,ＳＰＩ－３）和一些病力小岛,这些特殊基因构成了其致病性的分子基础。此外,它们还具有复杂,重叠的调节网络,可将环境信息传至调节蛋白,使基因表达随其感染宿主时动态环境的变化而变化。     

应用DNA芯片技术对禽致病性大肠杆菌可能致病基因体外表达水平的研究

应用DNA芯片研究禽致病性大肠杆菌可能致病基因的表达.构建禽致病性大肠杆菌毒力基因、潜在毒力基因的DNA芯片,应用基因芯片技术对同属O2血清型的禽高致病性大肠杆菌E058株和低致病性大肠杆菌E526株在体外LB培养基和鸡血清培养状态下进行差异表达分析.结果:在体外LB静置培养状态下,低致病株E526与高致病株E058相比共有16个差异基因,均为下调基因.在鸡血清静置培养中,E526与E058相比共有15个差异基因,均为下调基因.应用基因芯片成功筛选了禽致病性大肠杆菌在体外不同条件下的毒力基因及可能毒力基因中差异表达基因,表明一些铁摄取系统相关基因对APEC的毒力较重要,同时也筛选出了一些新的可能致病基因aes-1,aes-2,aes-3,aes-4,aes-6,aes-8,aes-10,aes-13,aes-15,aes-31等.     

尖孢镰刀菌致病机理和化感作用研究进展

尖孢镰刀菌引起的枯萎病在生产中的防控相当困难。通过总结国内外相关文献,综述近年来有关尖孢镰刀菌致病机理和化感作用的研究进展。尖孢镰刀菌通过分泌毒素和细胞壁降解酶共同致病,谱系特异性区域的存在是其致病性强和宿主范围广的主要原因;在尖孢镰刀菌各专化型中已分离出大量致病相关基因;其他植物和拮抗微生物(木霉菌、丛枝菌根真菌、非致病性尖孢镰刀菌以及植物生长促生菌)可以分泌化感物质,作用于宿主植物和尖孢镰刀菌,直接抑制尖孢镰刀菌的生长或激活宿主植物的防御反应。未来有关尖孢镰刀菌致病机理研究应该在基因组测序基础上构建精细的遗传图谱;对化感作用的研究应当深入探讨分子机理,利用高通量测序等技术在转录组或蛋白组水平上明确宿主植物抗枯萎病相关基因,同时利用分子标记辅助育种来筛选新的抗枯萎病品种。     

出血性大肠杆菌O157基因缺失疫苗株的构建及其免疫

出血性大肠杆菌O157感染是重要的新发食物源性传染病,主要致病特征之一是能引起人肠上皮细胞特征性的A/E损伤,A/E损伤主要是由LEE致病岛所编码的毒力因子所引起,ler是LEE致病岛毒力基因群的中心调节基因,对LEE致病岛所编码的毒力因子有正调控作用。O157:H7另一个毒力因子是由整合到染色体上的原噬菌体编码的Stx毒素。以O157:H786-24为始发菌株,利用自杀性质粒pCVD442和同源重组的原理构建了O157:H7的ler基因缺失突变菌株(缺失了ler基因中第73-351位的碱基,共279bp),并利用噬菌体消除技术筛选到消除了编码Stx的原噬菌体DNA的菌株,构建出了O157:H7ler/stx基因缺失突变弱毒菌株,并对该菌株的Vero细胞毒性、小鼠模型的安全性以及乳鼠的被动免疫保护作用进行了研究。结果表明,O157:H7ler/stx基因缺失突变菌株丧失了对Vero细胞的毒性作用,并丧失了对实验小鼠的致病性,具有良好的安全性。乳鼠被动免疫保护性实验表明,用该菌株免疫母鼠后,乳鼠通过吸吮母乳可以获得良好的被动免疫保护作用。因此本研究所构建的O157:H7ler/stx基因缺失突变弱毒菌株可作为预防EHEC O157:H7感染的疫苗候选株,为最终研究制出O157的基因工程菌苗奠定基础。     

Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution

Virulence genes of pathogenic bacteria, which code for toxins, adhesins, invasins or other virulence factors, may be located on transmissible genetic elements such as transposons, plasmids or bacteriophages. In addition, such genes may be part of particular regions on the bacterial chromosome, termed‘pathogenicity islands’(Pais). Pathogenicity islands are found in Gram-negative as well as in Gram-positive bacteria. They are present in the genome of pathogenic strains of a given species but absent or only rarely present in those of non-pathogenic variants of the same or related species. They comprise large DNA regions (up to 200 kb of DNA) and often carry more than one virulence gene, the G+C contents of which often differ from those of the remaining bacterial genome. In most cases, Pais are flanked by specific DNA sequences, such as direct repeats or insertion sequence (IS) elements. In addition, Pais of certain bacteria (e.g. uropathogenic Escherichia coli, Yersinia spp., Helicobacter pylori) have the tendency to delete with high frequencies or may undergo duplications and amplifications. Pais are often associated with tRNA loci, which may represent target sites for the chromosomal integration of these elements. Bacteriophage attachment sites and cryptic genes on Pais, which are homologous to phage integrase genes, plasmid origins of replication or IS elements, indicate that these particular genetic elements were previously able to spread among bacterial populations by horizontal gene transfer, a process known to contribute to microbial evolution.     

利用相似致病菌中保守的致病菌特有基因预测新的毒力相关基因

目的:在致病机制相似的致病菌中寻找保守的致病菌特有基因,预测新的毒力相关基因。方法:首先选取致病机制相似的致病菌EHEC与EPEC,利用本实验室构建的包含115 152条致病菌特有基因片段的数据库进行本地Blast,得到致病菌特有基因,对致病菌特有基因在相似致病菌中的保守性进行分析,得到新的可能的毒力相关基因。结果:在6株EHEC菌中找到95条保守的致病菌特有基因,其中大部分为已知的毒力相关基因,还有许多可能的毒力相关基因;在9株相似致病菌(EHEC、EPEC)中找到10条保守的致病菌特有的蛋白基因,其中9条为已知的致病相关基因,1条为可能的致病相关基因。结论:应用本方法可以发现新的毒力基因,为后续对致病菌致病机制的实验研究奠定了基础。     

Agrocin-producing pathogenic and nonpathogenic biotype-3 strains ofAgrobacterium tumefaciens active against biotype-3 pathogens

Agrocin-producing pathogenic and nonpathogenic biotype-3 strains ofAgrobacterium tumefaciens were isolated from grapevine gall tissue. In vitro activity of the nonpathogenic agrocin producers was restricted to biotype-3 pathogens used. Pathogenic agrocin producers were active in vitro against biotype-3 agrocin-producing nonpathogens, non-agrocin-producing pathogens, and biotype-1 strains when cultivated on a modified Stonier's medium; on a medium designated AB, two strains stested showed no activity against agrocin-producing nonpathogens, but agrocin of one of these strains was active against other agrocin-producing pathogens. In a greenhouse experiment a marked tendency toward decreased gall formation by biotype-3 pathogens on grapevines was obtained when biotype-3 pathogens and nonpathogenic biotype-3 agrocin producers were applied to wounds simultaneously. In this experiment, agrocin-producting pathogens tended to be more virulent than non-agrocin-producing pathogens.     

Crossing the kingdom border: Human diseases caused by plant pathogens

Interactions between pathogenic microorganisms and their hosts are varied and complex, encompassing open-field scale interactions to interactions at the molecular level. The capacity of plant pathogenic bacteria and fungi to cause diseases in human and animal systems was, until recently, considered of minor importance. However, recent evidence suggests that animal and human infections caused by plant pathogenic fungi, bacteria and viruses may have critical impacts on human and animal health and safety. This review analyses previous research on plant pathogens as causal factors of animal illness. In addition, a case study involving disruption of type III effector-mediated phagocytosis in a human cell line upon infection with an opportunistic phytopathogen, Pseudomonas syringae pv. tomato, is discussed. Further knowledge regarding the molecular interactions between plant pathogens and human and animal hosts is needed to understand the extent of disease incidence and determine mechanisms for disease prevention.     

院内感染复数菌败血症的临床和耐药分析

目的 探讨院内感染复数菌败血症的临床特征、危险因素、致病菌分布及耐药情况。方法 回顾性分析1970～2004年经血培养和临床资料证实的126例院内感染的复数菌败血症。结果 院内感染复数菌败血症均发生在较严重的基础疾病上．创伤性手术和操作、广谱抗菌药物和免疫抑制剂的应用、放疗与化疗为该病的危险因素。院内感染复数菌败血症感染病死率达52％,致病菌以G^-菌占多数,合并真菌感染者死亡率高。致病菌多为耐药菌株。结论 院内感染复数菌败血症病情危重,病死率高,多系耐药菌株感染。应尽早治疗原发基础疾病,避免危险因素,严格掌握侵入性诊疗手段的运用指征,合理应用抗菌药物。并重视院内环境卫生,严格做好洗手、消毒等是防止耐药菌播散的主要措施。     

Horizontal gene and chromosome transfer in plant pathogenic fungi affecting host range

Plant pathogenic fungi adapt quickly to changing environments including overcoming plant disease resistance genes. This is usually achieved by mutations in single effector genes of the pathogens, enabling them to avoid recognition by the host plant. In addition, horizontal gene transfer (HGT) and horizontal chromosome transfer (HCT) provide a means for pathogens to broaden their host range. Recently, several reports have appeared in the literature on HGT, HCT and hybridization between plant pathogenic fungi that affect their host range, including species of Stagonospora/Pyrenophora, Fusarium and Alternaria. Evidence is given that HGT of the ToxA gene from Stagonospora nodorum to Pyrenophora tritici-repentis enabled the latter fungus to cause a serious disease in wheat. A nonpathogenic Fusarium species can become pathogenic on tomato by HCT of a pathogenicity chromosome from Fusarium oxysporum f.sp lycopersici, a well-known pathogen of tomato. Similarly, Alternaria species can broaden their host range by HCT of a single chromosome carrying a cluster of genes encoding host-specific toxins that enabled them to become pathogenic on new hosts such as apple, Japanese pear, strawberry and tomato, respectively. The mechanisms HGT and HCT and their impact on potential emergence of fungal plant pathogens adapted to new host plants will be discussed.     

临床常见病原菌的分布及耐药性分析

目的了解我院患者常见病原菌分布及其耐药情况,指导临床治疗,合理使用抗生素。方法将我院2006年~2008年分离的临床病原菌分布及其耐药情况进行回顾性分析。结果我院病原菌分布以革兰阴性杆菌为主,占40.9%,革兰阳性球菌占34.4%,真菌占24.7%,居于革兰阴性杆菌前3位的菌群是大肠埃希菌、变形杆菌属和克雷伯菌属;居于革兰阳性球菌前3位的菌群是凝固酶阴性葡萄球菌、肠球菌属和链球菌属;各菌群中抗菌药物的耐药率均有上升,部分菌株呈多重耐药。结论革兰阴性杆菌已成为医院感染的最常见病原菌,对抗生素耐药日益严重,医院应重视病原菌的耐药性监测,及时掌握细菌耐药的动态,指导临床合理使用抗生素,防止医院感染的发生。     

北京地区非洲菊叶斑病病原菌鉴定

采用离体叶片接种致病性测定、形态学观察和分子鉴定方法对非洲菊叶斑病病原进行鉴定。从北京某花卉基地采集非洲菊叶斑病样,分离获得22个真菌分离物,分别记作GL1-GL22。经过致病性试验证实,分离物GL14和GL22为非洲菊叶斑病病原菌。经形态学鉴定,GL14为细极链格孢Alternaria tenuissima,GL22为链格孢Alternaria alternata。采用真菌通用引物对GL14和GL22 rDNA的ITS区进行PCR扩增,并将测序结果在GenBank中进行同源性比对分析,分子鉴定与形态学鉴定结果一致。     

When ferroptosis meets pathogenic infections

Apoptosis, necrosis, or autophagy are diverse types of regulated cell death (RCD), recognized as the strategies that host cells use to defend against pathogens such as viruses, bacteria, or fungi. Pathogens can induce or block different types of host cell RCD, promoting propagation or evading host immune surveillance. Ferroptosis is a newly identified RCD. Evidence has demonstrated how pathogens regulate ferroptosis to promote their replication, dissemination, and pathogenesis. However, the interaction between ferroptosis and pathogenic infections still needs to be completely elucidated. This review summarizes the advances in the interaction between pathogenic infections and host ferroptotic processes, focusing on the underlying mechanisms of how pathogens exploit ferroptosis, and discussing possible therapeutic measures against pathogen-associated diseases in a ferroptosis-dependent manner.     

Transfer of multiple drug resistance plasmids between bacteria of diverse origins in natural microenvironments.

Plasmids harboring multiple antimicrobial-resistance determinants (R plasmids) were transferred in simulated natural microenvironments from various bacterial pathogens of human, animal, or fish origin to susceptible strains isolated from a different ecological niche. R plasmids in a strain of the human pathogen Vibrio cholerae O1 E1 Tor and a bovine Escherichia coli strain were conjugated to a susceptible strain of the fish pathogenic bacterium Aeromonas salmonicida subsp. salmonicida in marine water. Conjugations of R plasmids between a resistant bovine pathogenic E. coli strain and a susceptible E. coli strain of human origin were performed on a hand towel contaminated with milk from a cow with mastitis. A similar conjugation event between a resistant porcine pathogenic E. coli strain of human origin was studied in minced meat on a cutting board. Conjugation of R plasmids between a resistant strain of the fish pathogenic bacterium A. salmonicida subsp. salmonicida and a susceptible E. coli strain of human origin was performed in raw salmon on a cutting board. R plasmids in a strain of A. salmonicida subsp. salmonicida and a human pathogenic E. coli strain were conjugated to a susceptible porcine E. coli strain in porcine feces. Transfer of the different R plasmids was confirmed by plasmid profile analyses and determination of the resistance pattern of the transconjugants. The different R plasmids were transferred equally well under simulated natural conditions and under controlled laboratory conditions, with median conjugation frequencies ranging from 3 x 10(-6) to 8 x 10(-3). The present study demonstrates that conjugation and transfer of R plasmids is a phenomenon that belongs to the environment and can occur between bacterial strains of human, animal, and fish origins that are unrelated either evolutionarily or ecologically even in the absence of antibiotics. Consequently, the contamination of the environment with bacterial pathogens resistant to antimicrobial agents is a real threat not only as a source of disease but also as a source from which R plasmids can easily spread to other pathogens of diverse origins.