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摘要:目的 通过应用全基因组测序(whole genome sequencing, WGS)技术分析某三级医疗机构耐碳青霉烯类抗生素鲍曼不 动杆菌(carbapenem-resistant Acinetobacter baumannii, CRAB)的耐药基因、毒力因子及同源性。方法 收集该院2020年1月至3月 重症监护病房(Intensive care unit, ICU)、神经外科分离的11株医院感染CRAB菌株,通过二代测序平台进行全基因组测序, 应用 基因组流行病学中心(Center for genomic epidemiology, CGE)ResFinder 4. 0软件分析其耐药基因型,并应用MORPHEUS在线制作 热图,应用毒力因子数据库(virulence factors of pathogenic bacteria, VFDB)VFanalyzer软件筛选毒力因子,应用MLST软件检测菌 株的ST型,应用Kaptive软件检测荚膜型,应用CSI Phylogeny 1. 4软件及FigTree v1. 4. 4软件构建最大似然树(maximum likelihood tree, MLT)以分析其同源性。结果 11株CRAB对亚胺培南、美罗培南、头孢菌素、环丙沙星均呈现耐药,而对阿米卡星、左氧 氟沙星耐药的菌株株数较少。11株CRAB共检测出18种耐药基因,11株同时携带碳青霉烯酶耐药基因blaOXA-23和blaOXA-66,β-内酰 胺酶耐药基因以blaTEM-1D和blaADC-25为主,大部分菌株携带多种外排泵相关耐药基因及抗菌药物修饰酶耐药基因。11株CRAB均携 带多种毒力因子,包括外膜孔蛋白、脂多糖、生物膜、外排泵、磷脂酶和效应蛋白等,如OmpA、Lps、Csu、Pga、Ade、Plc、 Bas、Bau、Ent、Hem、Aba、Bfm、Pbp和Kat等。11株CRAB均为ST2-K22型,同源性分析结果显示C组内同源性关系相近,存 在院内传播的可能。结论 该院CRAB的耐药性、毒力特征复杂多样,同源性分析显示该院存在1种优势克隆株,该克隆株有医 院内传播的风险。  相似文献   
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《Research in microbiology》2016,167(4):262-271
Understanding the infection mechanisms of pathogens will lead to better management of the associated diseases. The flagella of these pathogens play significant roles not only in bacterial motility, but also in virulence. In the present study, two genes involved in flagella construction, fliJ and fliI of Pseudomonas cichorii, were analyzed. The results revealed that these genes are vital for flagella formation and play significant roles not only in motility, but also in virulence. When we inoculated host plants with fliI- and fliJ-defective mutants (ΔfliJ and ΔfliI) through the dipping method, the degree of disease severity caused by both mutants was significantly reduced compared to those of the wild-type. However, the virulence of ΔfliI was stronger than that of ΔfliJ. Electron microscope observation, and swarming and leaf attachment assays indicated a reduced number of flagella in ΔfliI, but not complete absence, because of the presence of another copy of fliI. Furthermore, a vacuum infiltration assay revealed that flagella are indispensable in the pre- and post-penetration stages for complete virulence. Overall, we created semi-defective (ΔfliI) and completely defective (ΔfliJ) mutants and elucidated the fact that flagella play significant roles in virulence of the pathogen at different stages of the infection process.  相似文献   
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Avian colibacillosis, characterized by black proventriculus and caused by avian pathogenic Escherichia coli (APEC) with an uncommon O142 serogroup, was diagnosed in young broiler breeders. Colonization and persistence assays performed in 7-day-old broilers showed that the bacterial load of the APEC 4d/9-1 O142 proventricular isolate in the lung was about 10-fold higher than that of the APEC 4d/9-1 O142 heart blood isolate (P < 0.01), and about 100-fold higher in the heart blood, livers, spleens, kidneys, and proventriculi of inoculated broilers (P < 0.001). When 32 common virulence genes of APEC were tested, the two isolates had nearly identical profiles, except that only the APEC 4d/9-1 O142 proventricular isolate carried the feoB gene. Furthermore, 100% mortality was observed in both 1-day-old Arbor Acres (AA) broilers and 1-day-old specific-pathogen-free (SPF) chickens inoculated with 106 colony-forming units of the APEC 4d/9-1 O142 proventricular isolate. However, black proventriculus was only observed in the dead AA broilers, consistent with the clinical occurrence of the disease. This implies that the black proventriculi seen in the dead birds, caused by the APEC 4d/9-1 O142 proventricular isolate, was breed-specific. Both the APEC 4d/9-1 O142 proventricular and heart blood isolates belong to phylogroup B2. However, the former was assigned to ST131 and the latter to ST2704 with multilocus sequence typing, demonstrating the genetic heterogeneity of these two bacterial isolates, although they were derived from the same dead broiler. These results suggest that the O142 APEC isolate was the main pathogenic agent for black proventriculi in 7-day-old broiler breeders.  相似文献   
16.
Coccidioides is the causative agent of a potentially life-threatening respiratory disease of humans. A feature of this mycosis is that pH measurements of the microenvironment of pulmonary abscesses are consistently alkaline due to ammonia production during the parasitic cycle. We previously showed that enzymatically active urease is partly responsible for elevated concentrations of extracellular ammonia at sites of lung infection and contributes to both localized host tissue damage and exacerbation of the respiratory disease in BALB/c mice. Disruption of the urease gene (URE) of Coccidioides posadasii only partially reduced the amount of ammonia detected during in vitro growth of the parasitic phase, suggesting that other ammonia-producing pathways exist that may also contribute to the virulence of this pathogen. Ureidoglycolate hydrolase (Ugh) expressed by bacteria, fungi and higher plants catalyzes the hydrolysis of ureidoglycolate to yield glyoxylate and the release CO2 and ammonia. This enzymatic pathway is absent in mice and humans. Ureidoglycolate hydrolase gene deletions were conducted in a wild type (WT) isolate of C. posadasii as well as the previously generated Δure knock-out strain. Restorations of UGH in the mutant stains were performed to generate and evaluate the respective revertants. The double mutant revealed a marked decrease in the amount of extracellular ammonia without loss of reproductive competence in vitro compared to both the WT and Δure parental strains. BALB/c mice challenged intranasally with the Δughure mutant showed 90% survival after 30 days, decreased fungal burden, and well-organized pulmonary granulomas. We conclude that loss of both Ugh and Ure activity significantly reduced the virulence of this fungal pathogen.  相似文献   
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Erwinia amylovora causes economic losses that affect pear and apple production in Morocco. Here, we report comparative genomics of four Moroccan E. amylovora strains with the European strain CFBP1430 and North-American strain ATCC49946. Analysis of single nucleotide polymorphisms (SNPs) revealed genetic homogeneity of Moroccan's strains and their proximity to the European strain CFBP1430. Moreover, the collected sequences allowed the assembly of a 65 kpb plasmid, which is highly similar to the plasmid pEI70 harbored by several European E. amylovora isolates. This plasmid was found in 33% of the 40 E. amylovora strains collected from several host plants in 2009 and 2010 in Morocco.  相似文献   
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以致病基因作为靶点的药物为我们提供了从基因水平预防、治疗疾病的可能,筛选致病基因,成为攻克细菌、病毒乃至遗传因素导致的疾病的一个重要课题。筛选方法不断地改革与创新,针对不同的研究目的需要合理地选择筛选方法,本文简要介绍几种常用的细菌致病基因的筛选方法。  相似文献   
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Cytolethal distending toxin (CDT) is a bacterial toxin that initiates a eukaryotic cell cycle block at the G2 stage prior to mitosis. CDT is produced by a number of bacterial pathogens including: Campylobacter species, Escherichia coli, Salmonella enterica serovar Typhi, Shigella dystenteriae, enterohepatic Helicobacter species, Actinobacillus actinomycetemcomitans (the cause of aggressive periodontitis), and Haemophilus ducreyi (the cause of chancroid). The functional toxin is composed of three proteins; CdtB potentiates a cascade leading to cell cycle block, and CdtA and CdtC function as dimeric subunits, which bind CdtB and delivers it to the mammalian cell interior. Once inside the cell, CdtB enters the nucleus and exhibits a DNase I-like activity that results in DNA double-strand breaks. The eukaryotic cell responds to the DNA double-strand breaks by initiating a regulatory cascade that results in cell cycle arrest, cellular distension, and cell death. Mutations in CdtABC that cause any of the three subunits to lose function prevent the bacterial cell from inducing cytotoxicity. The result of CDT activity can differ somewhat depending on the eukaryotic cell types affected. Epithelial cells, endothelial cells, and keratinocytes undergo G2 cell cycle arrest, cellular distension, and death; fibroblasts undergo G1 and G2 arrest, cellular distension, and death; and immune cells undergo G2 arrest followed by apoptosis. CDT contributes to pathogenesis by inhibiting both cellular and humoral immunity via apoptosis of immune response cells, and by generating necrosis of epithelial-type cells and fibroblasts involved in the repair of lesions produced by pathogens resulting in slow healing and production of disease symptoms. Thus, CDT may function as a virulence factor in pathogens that produce the toxin.  相似文献   
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Gastric adenocarcinoma is a global health concern, and Helicobacter pylori (H. pylori) infection is the main risk factor for its occurrence. Of note, the immune response against the pathogen seems to be a determining factor for gastric oncogenesis, and increasing evidence have emphasized several host and bacterium factors that probably influence in this setting. The development of an inflammatory process against H. pylori involves a wide range of mechanisms such as the activation of pattern recognition receptors and intracellular pathways resulting in the production of proinflammatory cytokines by gastric epithelial cells. This process culminates in the establishment of distinct immune response profiles that result from the cytokine-induced differentiation of T naïve cells into specific T helper cells. Cytokines released from each type of T helper cell orchestrate the immune system and interfere in the development of gastric cancer in idiosyncratic ways. Moreover, variants in genes such as single nucleotide polymorphisms have been associated with variable predispositions for the occurrence of gastric malignancy because they influence both the intensity of gene expression and the affinity of the resultant molecule with its receptor. In addition, various repercussions related to some H. pylori virulence factors seem to substantially influence the host immune response against the infection, and many of them have been associated with gastric tumorigenesis.  相似文献   
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