Molecular basis of macrolide resistance among Pasteurella multocida and Mannheimia haemolytica isolates
多杀性巴氏杆菌和溶血性曼海姆氏菌对大环内酯类药物耐药的分子基础
基本信息
- 批准号:144713519
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2009
- 资助国家:德国
- 起止时间:2008-12-31 至 2017-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Aims of the study on macrolide-resistant Pasteurella (P.) multocida und Mannheimia (M.) haemolytica isolates were (1) the identification of the resistance mechanisms involved, (2) the characterization of the resistance genes or resistance-mediating mutations present, and (3) the analysis of the regulation and transferability of the resistance determinants, as well as the investigation of potential cross-resistances mediated by the respective resistance determinants. In the first period of the project SCHW382/10-1, three novel macrolide resistance genes, erm(42), msr(E) and mph(E), could be identified in P. multocida und M. haemolytica isolates from North America. The genes were located on a novel mobile genetic element, the integrative and conjugative element ICEPmu1. This ICE had a size of 82 kb and harbored in total twelve antimicrobial resistance genes in two resistance gene regions of approximately 15.7 and 9.8 kb in size. ICEPmu1 transferred with a high frequency of 2.9 x 10-6 to 1 x 10-4 from the original P. multocida isolate into P. multocida, M. haemolytica and Escherichia coli recipient strains where it conferred a multiresistance phenotype. PCRs were developed for a fast and reliable identification of these the novel resistance genes. Further studies showed that the genes also conferred resistance to tildipirosin or gamithromycin. Tildipirosin and gamithromycin represent the latest antimicrobial agents of the macrolide class which have been approved in 2011 for the treatment of respiratory tract infections in cattle and pigs. The co-localization of twelve resistance genes on a mobile element capable of high frequency self-transfer across genus boundaries represents a serious threat and drastically limits the options of an efficient antimicrobial therapy of respiratory tract infections in food-producing animals.The aims of the follow-up study are (1) to identify the macrolide resistance mechanism(s) in M. haemolytica isolates that do not harbor any of the new macrolide resistance genes, (2) to analyze ICEs in Pasteurellaceae for structural variabilities in their resistance gene regions and to investigate the potential of ICEs as accumulators and distributers of resistance genes, but also (3) to analyze the first macrolide-resistant Pasteurellaceae isolates from Germany.The results of the first study period provided important basic information on resistance to macrolide antibiotics in Pasteurellaceae. The follow-up study aims at the identification of other so far unknown resistance genes and/or mechanisms. While multiresistance-conferring ICEs were identified for the first time in Pasteurellaceae during the first study, the follow-up study will provide in-depth insight into the structural variability of these novel mobile elements as well as allow for a prediction of further developments towards pan-resistant Pasteurellaceae which cannot be treated anymore with antimicrobial agents.
对大环内酯类耐药巴斯德氏菌 (P.) 多杀性和曼海姆氏菌 (M.) 溶血性菌株的研究目的是 (1) 鉴定所涉及的耐药机制,(2) 存在的耐药基因或耐药介导突变的特征,以及 (3) 分析耐药决定因素的调节和可转移性,以及调查由耐药性决定因素介导的潜在交叉耐药性。 各自的阻力决定因素。在 SCHW382/10-1 项目的第一阶段,可以在来自北美的多杀性巴氏杆菌和溶血性巴氏杆菌分离株中鉴定出三种新的大环内酯类抗性基因:erm(42)、msr(E) 和 mph(E)。这些基因位于一个新的可移动遗传元件上,即整合和接合元件 ICEPmu1。该ICE的大小为82 kb,在大小约为15.7和9.8 kb的两个耐药基因区域中总共包含12个抗菌素耐药基因。 ICEPmu1 以 2.9 x 10-6 至 1 x 10-4 的高频率从原始多杀性巴氏杆菌分离物转移到多杀性巴氏杆菌、溶血性支原体和大肠杆菌受体菌株中,并赋予多重抗性表型。 PCR 的开发是为了快速可靠地鉴定这些新型抗性基因。进一步的研究表明,这些基因还赋予替地罗星或加米霉素耐药性。替地匹罗辛和加米霉素是最新的大环内酯类抗菌药物,于 2011 年被批准用于治疗牛和猪的呼吸道感染。能够跨属界高频自我转移的移动元件上的十二个耐药基因的共定位代表了严重的威胁,并极大地限制了食用动物呼吸道感染的有效抗菌治疗的选择。后续研究的目的是(1)确定不含有任何新的溶血分枝杆菌分离株的大环内酯耐药机制。 大环内酯类抗性基因,(2) 分析巴氏杆菌科中的 ICE,了解其抗性基因区域的结构变异,并研究 ICE 作为抗性基因积累者和分发者的潜力,而且 (3) 分析来自德国的第一个大环内酯类抗性巴氏杆菌分离株。第一个研究阶段的结果为大环内酯类抗生素耐药性提供了重要的基础信息。 巴氏杆菌科。后续研究旨在鉴定其他迄今为止未知的抗性基因和/或机制。虽然在第一项研究中首次在巴氏杆菌科中发现了赋予多重耐药性的 ICE,但后续研究将深入了解这些新型移动元件的结构变异性,并预测无法再用抗菌药物治疗的泛耐药性巴氏杆菌的进一步发展。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Professor Dr. Stefan P. Schwarz其他文献
Professor Dr. Stefan P. Schwarz的其他文献
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{{ truncateString('Professor Dr. Stefan P. Schwarz', 18)}}的其他基金
Identification of factors that led to the development of pig-associated epidemic MRSA clone
导致猪相关流行性 MRSA 克隆发展的因素的鉴定
- 批准号:
389553136 - 财政年份:2018
- 资助金额:
-- - 项目类别:
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Molecular basis of florfenicol resistance in staphylococci
葡萄球菌对氟苯尼考耐药的分子基础
- 批准号:
5227516 - 财政年份:1999
- 资助金额:
-- - 项目类别:
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Genetic basis, transferability and co-selection of macrolide resistance among Mannheimia haemolytica and Pasteurella multocida from respiratory tract infections of cattle and swine
牛和猪呼吸道感染溶血曼海姆菌和多杀性巴氏杆菌大环内酯类药物耐药性的遗传基础、可转移性和共选择
- 批准号:
513529774 - 财政年份:
- 资助金额:
-- - 项目类别:
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