铜绿假单胞杆菌QS相关基因CDNA芯片的研制及基因差异表达的研究

发布时间：2018-03-29 23:11

本文选题：铜绿假单胞　切入点：密度感应信号系统　出处：《第二军医大学》2006年硕士论文

【摘要】：绿假单胞菌(俗称绿脓杆菌,Pseudomonas aeruginosa)在自然界分布广泛,在人的正常皮肤上也有分布,是人类3大机会致病菌之一。也是院内感染的主要病原之一。绿脓杆菌感染的治疗相对困难,其突出的主要原因是由于本菌对抗生素和消毒剂的内在耐受性。目前已完成基因组序列的测定,其基因组全长达6.3Mbp,这样巨大的基因组信息,可产生更多的调控各生理功能的蛋白产物,扩展了绿脓杆菌对各种环境的适应能力。研究表明,绿脓杆菌细胞外毒力因子的产生并非单个细菌细胞所为而是达到一定密度的细胞群体所为:从少量细菌中分离出来的细胞外毒力因子可激发宿主免疫反应来中和这些化合物;而整个菌群一旦达到某种密度,其毒力基因协调表达使绿脓杆菌分泌的细胞外因子达到足以克服宿主防御系统的高水平。即使使用合适的抗生素治疗也不能阻止这一进程。因此该过程必须在毒力基因协调表达之前在早期得到阻断。这种以细胞密度依赖方式协调表达特异性基因的现象称为法定菌数信号传感应答(quorum sensing and response)。绿脓杆菌通过密度感应信号系统经由高丝氨酰内酯(acyl-homoserine lactone,acyl-HSL)信号分子来传送信息、监控细菌细胞密度从而控制其细胞外毒力因子的产生。表明了QS信号系统是绿脓杆菌的独立细胞分化成为复杂的多细胞结构所必需的,并发现多聚磷酸激酶(polyphosphate kinase,ppk)在生物膜的形成、毒力因子的产生、绿脓杆菌的运动方式方面起着重要的作用,说明生物膜的形成和毒力因子的产生是由某些共同的基因表达进行调控的。 PA的主要耐药机制包括以下两个方面: (1) 生物被膜(biofilm,BF)在细菌耐药方而发挥着十分重要的作用。BF状态的细菌对抗菌药物的抵抗力比浮游状态细菌强1000倍。PA的BF耐药机制复杂,主要有以下个方而:①限制抗生素渗透。在BF状态卜细菌分泌大量细胞外多糖(EPS)基质,EPS可粘结单个细菌而形成细菌团快,即微菌落微菌落可以由单一菌种或由多种微生物发育而成。在这些微菌落内,细菌发育成为功能上异质性的有组织群体。大量微菌落使BF加厚,EPS的产生对BF结构的发展十分重要。己证实EPS基质对某些抗生素和杀虫药有明显的阻碍作用。目前普遍认为,PA
[Abstract]:Pseudomonas aeruginosa (Pseudomonas aeruginosa) is one of the three major opportunistic pathogens in human skin, and is one of the major pathogens of nosocomial infection. The treatment of Pseudomonas aeruginosa infection is relatively difficult. The main cause is the inherent tolerance of the bacterium to antibiotics and disinfectants. At present, the genome sequence has been sequenced, and the length of genome reaches 6.3 Mbp. such huge genomic information can produce more protein products regulating various physiological functions and expand the adaptability of Pseudomonas aeruginosa to various environments. Research shows that. The production of extracellular virulence factors of Pseudomonas aeruginosa is not the result of a single bacterial cell but a certain density of cell population: extracellular virulence factor isolated from a small number of bacteria can stimulate host immune reaction to neutralize these compounds; And once the entire flora reaches a certain density, The coordinated expression of virulence genes results in a high level of extracellular factors secreted by Pseudomonas aeruginosa to overcome the host defense system. Even appropriate antibiotic therapy cannot prevent this process. This phenomenon of coordinated expression of specific genes in a density-dependent manner is known as quorum sensing and response. Pseudomonas aeruginosa is expressed through a density-sensitive signal system. The message is transmitted via a signal molecule called acyl-homoserine lactoneacyl-HSLs, Monitoring bacterial cell density to control the production of extracellular virulence factors suggests that QS signaling systems are necessary for the isolated cells of Pseudomonas aeruginosa to differentiate into complex multicellular structures. It was also found that polyphosphokinase polyphosphate (PPA) plays an important role in the formation of biofilm, the production of virulence factors, and the motility of Pseudomonas aeruginosa. It is suggested that the formation of biofilm and the production of virulence factors are regulated by some common gene expression. The main drug resistance mechanisms of PA include the following two aspects:. The biofilm BFs play a very important role in bacterial drug resistance. The resistance of bacteria in BF state to antimicrobial agents is 1000 times stronger than that of planktonic bacteria. In BF, bacteria secrete a large number of extracellular polysaccharides (EPSs). EPS can bind a single bacterium to form a colony of bacteria. That is, microcolonies can be developed from a single strain or from a variety of microbes. Bacterial development has become a functional heterogeneity of the organized population. A large number of microcolonies make BF thickened EPS production is very important to the development of BF structure. It has been confirmed that EPS matrix has a significant blocking effect on some antibiotics and pesticides. At present, it is generally considered that PA has a significant effect on the development of BF structure.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：Q789;R378.99

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