本文選題：銅綠假單胞　切入點(diǎn)：密度感應(yīng)信號系統(tǒng)　出處：《第二軍醫(yī)大學(xué)》2006年碩士論文

【摘要】：綠假單胞菌(俗稱綠膿桿菌,Pseudomonas aeruginosa)在自然界分布廣泛,在人的正常皮膚上也有分布,是人類3大機(jī)會(huì)致病菌之一。也是院內(nèi)感染的主要病原之一。綠膿桿菌感染的治療相對困難,其突出的主要原因是由于本菌對抗生素和消毒劑的內(nèi)在耐受性。 目前已完成基因組序列的測定,其基因組全長達(dá)6.3Mbp,這樣巨大的基因組信息,可產(chǎn)生更多的調(diào)控各生理功能的蛋白產(chǎn)物,擴(kuò)展了綠膿桿菌對各種環(huán)境的適應(yīng)能力。 研究表明,綠膿桿菌細(xì)胞外毒力因子的產(chǎn)生并非單個(gè)細(xì)菌細(xì)胞所為而是達(dá)到一定密度的細(xì)胞群體所為:從少量細(xì)菌中分離出來的細(xì)胞外毒力因子可激發(fā)宿主免疫反應(yīng)來中和這些化合物;而整個(gè)菌群一旦達(dá)到某種密度,其毒力基因協(xié)調(diào)表達(dá)使綠膿桿菌分泌的細(xì)胞外因子達(dá)到足以克服宿主防御系統(tǒng)的高水平。即使使用合適的抗生素治療也不能阻止這一進(jìn)程。因此該過程必須在毒力基因協(xié)調(diào)表達(dá)之前在早期得到阻斷。這種以細(xì)胞密度依賴方式協(xié)調(diào)表達(dá)特異性基因的現(xiàn)象稱為法定菌數(shù)信號傳感應(yīng)答(quorum sensing and response)。綠膿桿菌通過密度感應(yīng)信號系統(tǒng)經(jīng)由高絲氨酰內(nèi)酯(acyl-homoserine lactone,acyl-HSL)信號分子來傳送信息、監(jiān)控細(xì)菌細(xì)胞密度從而控制其細(xì)胞外毒力因子的產(chǎn)生。表明了QS信號系統(tǒng)是綠膿桿菌的獨(dú)立細(xì)胞分化成為復(fù)雜的多細(xì)胞結(jié)構(gòu)所必需的,并發(fā)現(xiàn)多聚磷酸激酶(polyphosphate kinase,ppk)在生物膜的形成、毒力因子的產(chǎn)生、綠膿桿菌的運(yùn)動(dòng)方式方面起著重要的作用,說明生物膜的形成和毒力因子的產(chǎn)生是由某些共同的基因表達(dá)進(jìn)行調(diào)控的。 PA的主要耐藥機(jī)制包括以下兩個(gè)方面: (1) 生物被膜(biofilm,BF)在細(xì)菌耐藥方而發(fā)揮著十分重要的作用。BF狀態(tài)的細(xì)菌對抗菌藥物的抵抗力比浮游狀態(tài)細(xì)菌強(qiáng)1000倍。PA的BF耐藥機(jī)制復(fù)雜,主要有以下個(gè)方而:①限制抗生素滲透。在BF狀態(tài)卜細(xì)菌分泌大量細(xì)胞外多糖(EPS)基質(zhì),EPS可粘結(jié)單個(gè)細(xì)菌而形成細(xì)菌團(tuán)快,即微菌落微菌落可以由單一菌種或由多種微生物發(fā)育而成。在這些微菌落內(nèi),細(xì)菌發(fā)育成為功能上異質(zhì)性的有組織群體。大量微菌落使BF加厚,EPS的產(chǎn)生對BF結(jié)構(gòu)的發(fā)展十分重要。己證實(shí)EPS基質(zhì)對某些抗生素和殺蟲藥有明顯的阻礙作用。目前普遍認(rèn)為,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.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：Q789;R378.99

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