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標題: 鮑氏不動桿菌臨床分離株之分子分型與其抗藥性基因島之解析
Molecular typing of clinical Acinetobacter baumannii isolates and identification of an antibiotic resistance island
作者: 林暄珮
Lin, Hsuan-Pei
關鍵字: Acinetobacter baumannii
multidrug resistant
resistance island
出版社: 生命科學系所
引用: Siroy A., Molle V., Lemaitre-Guillier C., Vallenet D., Pestel-Caron M., Cozzone A.J., Jouenne T., De E. 2005. Channel Formation by CarO, the Carbapenem Resistance-Associated Outer Membrane Protein of Acinetobacter baumannii. 49(12):4876-4883 Mussi M.A., Limansky A.S., Viale A.M. 2005. Acquisition of Resistance to Carbapenems in Multidrug-Resistant Clinical Strains of Acinetobacter baumannii: Natural Insertional Inactivation of a Gene Encoding a Member of a Novel Family of β-Barrel Outer Membrane Proteins. 49(4):1432-1440 Nitzan Y., Deutsch E.B., Pechanikov I. 2002. Diffusion of beta-lactam antibiotics through oligomeric or monomeric porin channels of some gram-negative bacteria. 45(6):446-55 Laurent Poirel and Patrice Nordmann. 2006. Genetic structures at the origin of acquisition and expression of the carbapenem-hydrolyzing oxacillinase Gene blaOXA-58 in Acinetobacter baumannii. AAC. 50(2): 1442-1448 Alessia Bertini, Laurent Poirel, Sandrine Bernabeu, Daniela Fortini, Laura Villa, Patrice Nordmann, Alessandra Carattoli. 2007. Multicopy blaOXA-58 gene as a source of high-level resistance to carbapenems in Acinetobacter baumannii. AAC. 01502-06: 2324-2328 Laurent Poirel, Sophie Marque, Claire Heritier, Christine Segonds, Gerard Chabanon, Patrice Nordmann. 2004. OXA-58, a novel class D bata-lactamase involved in resistance to carbapenems in Acinetobacter baumannii. AAC. 49(1): 202-208 Laurent Poirel and Patrice Nordmann. 2006. Carbapenem resistance in Acinetobacter baumannii : mechanisms and epidemiology. Clin. Microbiol. Infect. 12: 826-836 Jane F. Turton, M. Elania Ward, Neil Woodford, Mary E. Kaufmann, Rachel Pike, David M. Livermore, Tyrone L. Pitt. 2006. The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett. 258: 72-77 Navarro, S., Aleu, J., Jimenez, M., Boix, E., Cuchillo, C. M., and Nogues, M. V.. 2007. The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane. Cell. Mol. Life Sci. 65 (2008) 324-337 Torrent, M., Navarro, S., Moussaoui, M., Nogues, M. V., and Boix, E.. 2007. Eosinophil cationic protein high-affinity binding to bacteria-wall lipopolysaccharides and peptidoglycans. Biochemistry (in press) Huang, Y. C., Lin, Y. M., Chang, T. W., Wu, S. J., Lee, Y. S., Chang, D. T., Chen, C., Wu, S. H., and Liao, Y. D.. 2007. The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J. Biol. Chem. 282, 4626-4633 Carreras, E., Boix, E., Rosenberg, H. F., Cuchillo, C. M., and Nogues, M. V.. 2003. Both aromatic and cationic residues contribute to the membrane-lytic and bactericidal activity of eosinophil cationic protein. Biochemistry 42, 6636-6644 Levy, O.. 2000. 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Clin Microbiol Infect 12: 826-836 Tankovic, J., Legrand, P., De Gatines, G., Chemineau, V., Brun-Buisson, C., and Duval, J.. 1994. Characterization of a hospital outbreak of imipenem-resistant Acinetobacter baumannii by phenotypic and genotypic typing methods. Journal of Clinical Microbiology Nov. p. 2677-2681 Heritier, C., Poirel, L., Lambert, T., and Nordmann, P.. 2005. Contribution of acquired carbapenem-hydrolyzing oxacillinases to carbapenem resistance in Acinetobacter baumannii. Antimicrobial Agent and Chemotherapy (49) 8: 3198-3202 Jyothisri, K., Deepak, V., Rajeswari, M. R.. 1998. Purification and characterization of a major 40 kDa outer membrane protein of Acinetobacter baumannii. Federation of European Biochemical Societies Letters 443: 57-60 Rosenberg, H. F.. 1995. Recombinant human eosinophil cationic protein. The Journal of Biological Chemistry (270) 14: 7876-7881 Torrent, M., Navarro, S., Moussaoui, M., Nogues, V., and Boix, E.. 2007. Eosinophil cationic protein high-affinity binding to bacteria-wall lipopolysaccharides and peptidoglycans. Biochemistry (published on web) Navarro, S., Aleu, J., Jimenez, M., Boix, E., Cuchillo, C. M., and Nogues, M. V.. 2007. The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane. Cellular and Molecular Life Sciences (65) 324-337 Iacono, M., Villa, L., Fortini, D., Bordoni, R., Imperi, F., Bonnal, R., Sicheritz-Ponten, T., de Bellis, G., Visca, P., Cassone, A., and Carattoli, A.. 2008. Whole-genome pyrosequencing of an epidemic multidrug-resistant Acinetobacter baumannii strain belonging to the European clon II group. Antimicrobial Agents and Chemotherapy 52(7): 2612-2625 Shaikh, F., Spence, R. P., Levi, K., Ou, H. Y., Deng, Z., Towner, K. J., and Rajakumar, K.. 2008. ATPase genes of diverse multidrug-resistant Acinetobacter baumannii isolates frequently harbour integrated DNA. 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摘要: 鮑氏不動桿菌(Acinetobacter baumannii)是近年來佔院內感染大宗的病原菌株之一。其所具有的多重抗藥性(multidrug resistance)更成為臨床治療上的一大棘手問題。本研究首先藉由脈衝式電泳(Pulsed Field Gel Electrophoresis),解析同一位病患在同一次住院期間所分離出的菌株抗藥性表現改變的現象。挑選的二十二株菌分別為在2003~2007間,分別由十位病患的血液、尿液等所採集。在病患住院早期所採到的菌株原先不具抗生素抗藥性,然而經一段住院期間後,對多數抗生素產生抗性。從電泳結果發現,多數病患早期感染的不具抗藥性菌株和晚期採集之具有抗性的菌株為同屬同種之不同菌株。然而,一特殊例子顯示,同一株菌經過四天,即從不具抗藥性轉變為對多數抗生素產生抗性。 同時,亦進一步探討上述鮑氏不動桿菌院內感染案例中,是否有優勢菌株引起群突發的情況。實驗結果顯示,此四年之間由鮑氏不動桿菌引起的院內感染案例中,並無一優勢菌種存在。 此外,法國一團隊在一株臨床多重抗藥性鮑氏不動桿菌菌株AYE上發現到一個86 kb 的抗藥性基因島(resistance island)的結構,AbaR1。此抗性基因島在目前已被發現的類似基因結構中乃是最大的。本實驗先前研究成果顯示,一株採集自一地區醫院的臨床多重抗藥性菌株,編號1-43,具有類似AYE抗性基因島的結構。為了近一步探討1-43這株菌的基因結構,因此進行全基因組定序計劃。基因組定序結果顯示1-43帶有約213 kb 的類AbaR1之基因島結構。和AYE抗性基因島之結構相比較,1-43的基因島同樣位於一被插壞的ATPase上。而此被插壞的ATPase基因亦嘗被發現位於類似基因島結構的兩側,顯現此基因或許為鮑氏不動桿菌基因組上接受外來插入序列的一個熱點(hotspot)。然而,1-43基因島內部的基因結構和AbaR1內部的基因結果不盡相同。此外,透過共線性關係分析可發現,AYE和1-43具有極高的親緣性。由上述結果,我們推測AYE和1-43乃屬同源,然而在不同地區內各自演化成其獨特的基因結構。
Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in environment. From past decades, nosocomial multi-drug resistant A. baumannii is one of the major causes of hospital-acquired infection. To investigate whether if there is a predominant strain causing outbreaks in Chang-Hua Chrisitan Hospital from 2003 to 2007, twenty-two isolations collected from eleven patients were used for molecular typing by using Pulsed-Field Gel Electrophoresis (PFGE). In accordance with the susceptibility test, the result brought out a special phenomenon that strains isolated from the same patients at different infection stages showed phenotypic variation. To demonstrate if this was caused by either different strains or the same one but varied its phenotype under antibiotic pressure, profiles of PFGE were compared for those strains. From the genotype patterns of those analyzed strains, it tells that most of the patients were infected by different strains. However, one case shows that the patient was infected by the same strain but with varied genotype. The result also reveals that there is no predominant strain associated with hospital infections during the four years. Furthermore, genomic studies of a France isolated epidemic multi-drug resistant A. baumannii strain AYE demonstrated the existence of an 86-kb resistance island - AbaR1- clustering resistant genes. Also by the previous study in our laboratory, it was found that an A. baumannii multi-drug resistant strain 1-43 isolated from Chang-Hua Christian Hospital might possess the similar genetic structure. For further investigation, we started whole-genome sequencing of the strain 1-43. In accordance with the genome project data, a 213-kb resistance island was discovered. Compared to the resistance island AbaR1 genomic structure of the strain AYE in France, the resistance island of 1-43 has the same structure that it is flanked by a truncated ATPase gene, which might be a hotspot for insertion element in clinical A. baumannii spp.. However, the structure of resistance genes in the genomic island appears no identical to AbaR1. Besides, through the analysis of collinearity of the whole-genome of the strain AYE and 1-43, it suggested that these two clinical strains may share the same origin, but evolved separately to respective genomic structure.
其他識別: U0005-1908200915075000
Appears in Collections:生命科學系所



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