本文選題：大腸埃希菌 + 代謝組學��； 參考：《川北醫(yī)學院》2015年碩士論文

【摘要】：目的:統(tǒng)計分析大腸埃希菌(Escherichia coli,E.coli)感染者臨床資料及該菌株對三類15種抗菌藥物的耐藥性;用氣相色譜-質譜聯(lián)用(GC-MS)代謝組學的方法尋找與耐藥相關的差異性代謝產物和代謝網絡,并進一步探討其與耐藥之間的關系。方法:收集附屬醫(yī)院微生物室2012年12月至2014年10月臨床非同一患者同一部位重復分離的E.coli共126株,采用瓊脂二倍稀釋法檢測15種臨床常用抗菌藥物的最低抑菌濃度(minimal inhibitory concentration,MIC),并統(tǒng)計分析其感染者臨床資料和對抗菌藥物的耐藥性;篩選出對上述抗菌藥物全部敏感的6株(S組)和耐藥譜一致的4株(R組)作為代謝組學研究對象,利用GC-MS代謝組學的方法分析S組和R組中E.coli的代謝特征譜的差異,結合相關代謝通路數(shù)據(jù)庫和藥物機制尋找與耐藥相關的胞內差異性代謝產物和代謝網絡。結果:126例患者病史資料提示平均年齡為31.57±8.26歲,女性占51.59%(65/126)。病人有基礎性疾病者占10.32%(13/126),手術治療患者占23.89%(30/126)。入院前或入院后使用2種或以上的抗菌藥物治療者占56.35%(71/126)。平均住院時間為13.6天。標本來源科室分布:泌尿科(泌尿外科和腎內科)占42.86%(54/126),普外科和肛腸科占28.57%(36/126),婦產科占14.29%(18/126),呼吸科占8.73%(11/126)。標本取材來源以尿液和糞便最多,占54.76%(69/126),其次是手術創(chuàng)面和泌尿生殖道分泌物26.19%(33/126),痰液11.11%(14/126)。126株E.coli對頭孢唑林耐藥率最高(71.43%),頭孢呋辛、慶大霉素的耐藥率均在60%以上,對亞胺培南/西司他丁100%敏感,頭孢米諾、頭孢西丁和阿米卡星敏感性均在90%以上,敏感菌株占17.46%(22/126),多重耐藥(MDR)菌株占74.6%(94/126)。磷酸、丁二酸、磷酸乙醇胺、甘油、順-10-十七碳烯酸是S組和R組的差異性代謝產物,在R組的含量均低于S組。它們參與三羧酸循環(huán)、氧化磷酸化、氨基酸代謝、磷脂代謝等代謝通路。結論:(1)我院臨床分離E.coli對所試三類15種臨床常用抗菌藥物敏感率為17.46%,對兩類抗菌藥物耐藥率為9.74%,多重耐藥率為74.6%;亞胺培南、頭孢米諾、頭孢西丁和阿米卡星是治療耐藥E.coli感染的理想選擇,尤以亞胺培南為最。(2)磷酸、丁二酸、磷酸乙醇胺、甘油、順-10-十七碳烯酸是S組和R組的差異性代謝產物,它們在R組的含量皆低于S組,可能與R組中細菌在抗菌藥物長期壓力下的低代謝水平有關。(3)R組中丁二酸含量低可能是E.coli中TCA代謝失衡所致,進而干擾細胞的能量代謝,這大概與細菌的自我保護機制有關。(4)R組中磷酸、磷酸乙醇胺、甘油含量低可能是E.coli為逃避抗菌藥物打擊致使它們參與了細胞膜的空間構象改變,為其耐藥性的產生提供必要的生物學基礎。
[Abstract]:Objective: to analyze the clinical data of Escherichia coli (E.coli) infection and the resistance of the strain to three kinds of 15 kinds of antibiotics; to find the differential metabolites and metabolic networks related to drug resistance by gas chromatography-mass spectrometry (GC-MS), and to further explore the relationship between them and drug resistance. Methods: a total of 126 E.coli isolates from the same site in the hospital from December 2012 to October 2014 were collected, and the minimum inhibitory concentration (minimal inhibitory concentration, MIC) of 15 kinds of commonly used antibiotics was detected by agar two times dilution method, and the clinical data and antagonistic bacteria of the infected persons were analyzed and analyzed. Drug resistance; screening 6 strains (group S) and 4 strains (group R) that are all sensitive to the above antibiotics (group S) and resistance spectrum (group R). The metabolic characteristics of E.coli in group S and R group were analyzed by GC-MS metabolomics, and the related metabolic pathway database and drug mechanism were used to find the cell related to drug resistance. Results: the internal differential metabolites and metabolic networks. Results: the average age of 126 patients was 31.57 + 8.26 years, 51.59% (65/126), 10.32% (13/126) and 23.89% (30/126). 2 or more antibiotics were used before or after admission (71/126). The duration of hospitalization was 13.6 days. The distribution of specimen sources: Urology (Department of Urology and Nephrology) accounted for 42.86% (54/126), Department of general surgery and anorectal Department accounted for 28.57% (36/126), gynecologic and obstetrics accounted for 14.29% (18/126), 8.73% (11/126). The specimens were collected from urine and feces, accounting for 54.76% (69/126), followed by surgical wound and genitourinary tract. Secretion 26.19% (33/126), sputum 11.11% (14/126).126 strain E.coli was the highest (71.43%) resistant to cefazolin, and cefuroxime, gentamicin resistance rates were above 60%, imipenem / cefastatin 100%, ceftriaxone, cefoxitin and Amikacin were more sensitive than 90%, sensitive strains accounted for 17.46% (22/126), multidrug resistance (MDR). The strains accounted for 74.6% (94/126). Phosphoric acid, succinic acid, ethanolamine phosphate, glycerol, and CIS -10- seventeen carboxenoic acid were different metabolites in group S and R, and in R group were lower than that in group S. They were involved in the metabolic pathways of three carboxylic acid cycle, oxidative phosphorylation, amino acid metabolism, phospholipid metabolism, etc. conclusion: (1) the clinical separation of E.coli in our hospital on the three class 15 faces of the trial. The susceptibility rate of common antibiotics in bed was 17.46%, the rate of resistance to two types of antibiotics was 9.74%, and the rate of multidrug resistance was 74.6%. Imipenem, cephalosporin, cefoxitin and Amikacin were the ideal choice for the treatment of drug-resistant E.coli infection, especially imipenem. (2) phosphoric acid, succinic acid, ethanolamine phosphate, glycerol, and CIS -10- seventeen carbonic acid were the S group and the S group. The difference of metabolites in group R, which are lower in group R than in group S, may be related to the low metabolism level of bacteria in group R under long-term pressure of antimicrobial agents. (3) low content of succinic acid in group R may be caused by metabolic imbalance of TCA in E.coli, thereby interfering with cell energy metabolism, which is probably related to the self-protection mechanism of bacteria. (4) R group. The low content of phosphoric acid, ethanolamine phosphate and glycerin may be that E.coli is an escape from the anti antibacterial drug attack that causes them to participate in the spatial conformation change of the cell membrane, and provides the necessary biological basis for the production of its resistance.
【學位授予單位】：川北醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R446.5

【參考文獻】

相關期刊論文 前10條

1 梅輝;戴軍;劉文衛(wèi);凌霞;朱鵬飛;趙志軍;;高效液相色譜-串聯(lián)質譜法分析大腸桿菌代謝組中樣品提取方法的比較[J];分析化學;2011年04期

2 趙慶英;劉德夢;;大腸埃希菌耐藥機制研究進展[J];國外醫(yī)藥(抗生素分冊);2010年04期

3 洪伍華;李娟娟;林俊山;杭金玉;;某中醫(yī)院大腸埃希菌的分布和耐藥性分析[J];國際檢驗醫(yī)學雜志;2014年06期

4 張鳳珍;;大腸桿菌耐藥機制和消除耐藥性方法概述[J];內蒙古民族大學學報(自然科學版);2009年02期

5 張昭勇;張吉才;杜毅;;尿道感染大腸埃希菌對喹諾酮耐藥性及相關因素分析[J];臨床誤診誤治;2013年01期

6 楊治理;馮素清;;135例女性泌尿系感染患者細菌分布和耐藥性分析[J];檢驗醫(yī)學與臨床;2013年18期

7 王紅梅;;老年女性糖尿病患者合并尿路感染88例臨床分析[J];臨床合理用藥雜志;2009年10期

8 唐惠儒;王玉蘭;;代謝組研究[J];生命科學;2007年03期

9 梅輝;戴軍;劉文衛(wèi);宋鵬飛;吳敬;趙志軍;;LC-MS/MS法測定E.coli胞內24種代謝物[J];食品與發(fā)酵工業(yè);2011年05期

10 劉嶸明;梁麗亞;吳明科;姜岷;;微生物發(fā)酵生產丁二酸研究進展[J];生物工程學報;2013年10期

相關博士學位論文 前3條

1 唐文花;豬5個NADH相關基因和SMTN基因的分離、定位、時空表達和關聯(lián)分析[D];華中農業(yè)大學;2007年

2 武秋立;重組枯草芽孢桿菌生產核黃素發(fā)酵優(yōu)化及代謝組學研究[D];天津大學;2007年

3 周雅琳;煎炸油的品質評價及其極性化合物的快速檢測技術研究[D];西南大學;2009年

相關碩士學位論文 前6條

1 汪雨;土壤和水中有機氯農藥的分析方法研究[D];吉林農業(yè)大學;2006年

2 潘靖;大腸埃希菌耐藥性及耐藥基因檢測[D];大連醫(yī)科大學;2007年

3 祝金鳳;Ⅱ型菊酯類農藥廣譜特異性抗體的制備和多殘留免疫技術建立[D];揚州大學;2008年

4 王慧;白念珠菌中耐藥相關代謝物的比較代謝組學研究[D];第二軍醫(yī)大學;2012年

5 王凱;基于穩(wěn)定性同位素~(15)N示蹤和代謝譜分析技術的茶葉氮代謝研究[D];安徽農業(yè)大學;2012年

6 林家福;川北地區(qū)耐碳青霉烯鮑曼不動桿菌分子流行病學調查及碳青霉烯酶的檢測[D];川北醫(yī)學院;2013年

，

本文編號：2052466