Quinolone and multidrug resistance in Staphylococcus aureus

喹诺酮类药物与金黄色葡萄球菌的多重耐药性

基本信息

批准号：
8865521
负责人：
David C Hooper
金额：
$ 39.16万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8865521
关键词：
ATP-Binding Cassette Transporters Abscess Affect Affinity Amino Acid Sequence Antibiotic Resistance Antimicrobial Resistance Bacillus subtilis Bacitracin Binding Binding Proteins Biological Assay Candidate Disease Gene Cell Extracts Cell membrane Chloramphenicol Complex DNA Data Data Element Dyes Exposure to Family Fatty Acids Gelshift Analysis Gene Expression Genes Habitats Homologous Gene In Vitro Incubated Infection Iron Knock-out Lactococcus Link Macrolide-resistance Mass Spectrum Analysis Measures Mediating Membrane Modeling Multi-Drug Resistance Mus N-terminal Oxidative Stress Phenotype Predisposition Property Proteins Pump Quinolones Reagent Resistance Role Shuttle Vectors Side Signal Transduction Skin Skin Tissue Staphylococcus aureus Starvation Streptogramins System Testing Tetracyclines Topical Antibiotic Vacuum Work antimicrobial antimicrobial drug base efflux pump gene cloning genetic regulatory protein genome sequencing knockout gene long chain fatty acid magnetic beads mutant novel overexpression oxidation promoter quinolone resistance research study response

项目摘要

Bacterial efflux pumps can cause multidrug resistance when overexpressed, and mutational mechanisms of overexpression have involved an array of global regulators. In Staphylococcus aureus pumps NorA, NorB, and NorC can confer resistance to various quinolone antimicrobials along with chloramphenicol and some dyes. Pump Tet38 confers resistance to tetracyclines, and pump AbcA confers resistance to plactams with hydrophobic side-chains. Two global transcriptional regulators, MgrA and NorG, are known to have direct regulatory roles in the expression of various of these pumps. The work described below has focused on i) defining the regulatory mechanisms that control pump expression (including the complex interactions of various regulators), ii) determination of the role of pump expression in the adaptation of S. aureus to survival in an abscess, its most common cause of infection, iii) determination of the environmental signals that trigger pump expression, and iv) defining the natural substrates of these generally broad-spectrum pumps, for which antimicrobials may be incidental substrates.

过表达时，细菌外排泵会引起多药耐药性，并突变过表达的机制涉及一系列全球调节剂。在金黄色葡萄球菌泵中 NORA，NORB和NORC可以赋予各种喹诺酮抗菌剂以及氯霉素的耐药性还有一些染料。泵TET38赋予对四环素的抵抗力，泵ABCA赋予对Plactams的抵抗力与疏水的侧链。已知两个全球转录调节器MGRA和NORG已知在这些泵的各种泵的表达中具有直接的调节作用。下面描述的工作具有专注于i）定义控制泵表达的调节机制（包括复合物各种调节剂的相互作用），ii）确定泵表达在适应S.的作用金黄色葡萄球菌在脓肿中生存，其最常见的感染原因，iii）确定环境触发泵表达的信号，iv）定义这些通常广谱的自然基材泵，抗菌物可能是偶然的底物。