The mechanisms of evolution of antibiotic resistance in Staphylococcus aureus

金黄色葡萄球菌抗生素耐药性进化机制

• 批准号: 195232658
• 负责人: Professorin Dr. Gabriele Bierbaum
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/195232658?language=en
• 关键词: mechanisms; evolution; antibiotic; resistance; Staphylococcus

Staphylococcus aureus is one of the major resistant pathogens and, so far, it was able to acquire resistance to all antibiotics introduced into clinical practice. This grant application is focussed on the mechanisms involved in the evolution of resistance. Preliminary work has shown that exposure to antibiotics will not only select for resistant bacteria but may activate mutative mechanisms: In presence of ciprofloxacin and – to a lesser degree also in the presence of vancomycin – an increase in mutation frequency and an activation of mobile elements, e. g. IS-elements, was observed. The experiments proposed here will address the mechanisms involved in these processes. The major players include the SOS response and the response to cell wall inhibitory agents, the induction of error-prone polymerases, the regulation of the activity of stress sigma factor B and the regulation of transposition by antisense RNA. In addition, possible mutative effects of daptomycin and linezolid will be tested. The ultimate goal is to gain a detailed insight into these processes and thereby to increase the life-span of existing antibiotics.

金黄色葡萄球菌是主要的耐药病原体之一，到目前为止，它能够获得对所有引入临床实践的抗生素的耐药性。这项资助申请的重点是参与抗性进化的机制。初步研究表明，暴露于抗生素不仅会选择耐药细菌，而且可能激活突变机制：在环丙沙星存在下，以及在万古霉素存在下（程度较低），突变频率增加，移动的元件激活，例如。G.是元素，观察到。这里提出的实验将解决这些过程中涉及的机制。主要参与者包括SOS反应和对细胞壁抑制剂的反应、易错聚合酶的诱导、应激σ因子B活性的调节以及反义RNA对转座的调节。此外，还将检测达托霉素和利奈唑胺的可能突变效应。最终目标是详细了解这些过程，从而增加现有抗生素的寿命。

项目成果

Antibiotic-Induced Autoactivation of IS256 in Staphylococcus aureus

抗生素诱导金黄色葡萄球菌中 IS256 的自动激活

• DOI: 10.1128/aac.01585-13
• 发表时间: 2013
• 期刊: Antimicrobial Agents and Chemotherapy
• 影响因子: 4.9
• 作者: Schreiber F;Szekat C;Josten M;Sahl HG;Bierbaum G
• 通讯作者: Bierbaum G