Novel antibiotic resistance mechanisms in S. aureus

描述（由申请人提供）：金黄色葡萄球菌是导致 死亡率和经济损失在美国。我们已经描述了水杨酸诱导的多药 S.金黄色。水杨酸诱导的多药耐药表达为 表型上，并涉及减少的药物积累。以前固有的多药耐药的S。金黄色葡萄球菌归因于多药外排泵诺拉。我们提供的证据表明，水杨酸诱导的多药耐药机制是诺拉独立的。我们还将描述一个基因型S。金黄色葡萄球菌的多药耐药机制，结果选择抗微生物萜烯混合物松醇。这种机制也增加了对细胞壁活性抗葡萄球菌抗生素万古霉素的耐药性。我们打算确定是否假定的S。金黄色葡萄球菌多药外排泵Acr B和/或转录因子sigma B参与了金黄色葡萄球菌的多药耐药机制。我们实验室正在研究金黄色葡萄球菌。我们还计划证明，松醇选择的多药耐药突变体和水杨酸处理的细胞表达改变细胞壁生理。松奈醇选择性和水杨酸诱导性耐药相关基因的研究金黄色葡萄球菌将使用两种方法鉴定：二维凝胶电泳和用怀疑与金黄色葡萄球菌多药耐药相关的基因构建的DNA子阵列。金黄色。我们推测S.金黄色葡萄球菌将涉及大量的基因和基因产物。我们还推测，S.金黄色葡萄球菌将在以下的多药耐药性表达中起作用：i.）正常S.金黄色葡萄球菌细胞; ii.）松醇选择突变体的S.金黄色葡萄球菌;和iii.）水杨酸诱导的S.金黄色葡萄球菌细胞与沙门氏菌内在多药耐药机制相关的新组分。金黄色葡萄球菌可用作开发用于预防抗生素耐药性的抗菌药物的靶点。金黄色葡萄球菌的产生或停止其生长。涉及活动性疾病的金黄色葡萄球菌。这项研究也将有助于不断增长的知识体系的革兰氏阳性球菌细胞与杀生物剂和抗生素的相互作用。

DESCRIPTION (provided by applicant): Staphylococcus aureus is responsible for staggering mortality and financial loss in the U.S. We have characterized a salicylate-inducible multidrug resistance mechanism in S. aureus. Salicylate-induced multidrug resistance is expressed phenotypically and involves reduced drug accumulation. Previously intrinsic multidrug resistance in S. aureus was attributed to the multidrug efflux pump NorA. We provide evidence that demonstrates that the salicylate-induced multidrug resistance mechanism is NorA-independent. We will also characterize a genotypic S. aureus multidrug resistant mechanism that results as a consequence of selection for resistance to the antimicrobial terpene mixture pinesol. This mechanism also increases resistance to the cell wall active antistaphylococcal antibiotic vancomycin. We intend to determine if the putative S. aureus multidrug efflux pump AcrB and/or the alternative transcription factor sigma B play roles in the multidrug resistance mechanisms of S. aureus being studied in our laboratories. We also plan to demonstrate that pinesol-selected multidrug resistant mutants and salicylate treated cells express altered cell wall physiology. Genes involved with pinesol-selected and salicylate-inducible multidrug resistance mechanisms of S. aureus will be identified using two procedures: Two-dimensional gel electrophoresis and a DNA subarray constructed with genes suspected to be associated with multidrug resistance in S. aureus. We hypothesize that multidrug resistance expression by S. aureus will involve a large collection of genes and gene products. We also hypothesize that the putative multidrug efflux pump AcrB and alternative transcription factor sigma B of S. aureus will play a role in the multidrug resistance expression of: i.) normal S. aureus cells; ii.) pinesol-selected mutants of S. aureus; and iii.) salicylate-induced S. aureus cells. Novel components associated with intrinsic multidrug resistance mechanisms in S. aureus might be used as targets in the development of antimicrobials used to either prevent antibiotic resistant S. aureus from arising or to halt the growth of S. aureus involved with active disease. This research will also contribute to the growing body of knowledge on the interaction of the Gram-positive coccal cells with biocides and antibiotics.