由法定感应控制的药物出口商出口利福平对葡萄球菌生物膜具有很强的活性

IF 14.6 1区 医学 Q1 CELL BIOLOGY
Yao Liu, Lei He, Ryan Liu, Dylan J. Burgin, Min Li, Michael Otto
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引用次数: 0

摘要

留置医疗器械上的生物膜感染是卫生保健相关感染和死亡的主要原因。这些感染大多是由葡萄球菌引起的。由于与非特异性抗菌素耐药性显著增加有关,生物膜形成呈现出持续的临床挑战。与大多数抗生素不同,利福平对葡萄球菌生物膜感染有活性;然而,其机制尚不清楚。通过体外实验和小鼠生物膜感染模型,我们在这里表明利福平比其他抗生素对葡萄球菌agr突变体更有效,这种突变体与严重的生物膜感染有关,因为它们产生延长的生物膜。我们发现这种优势源于agr控制的利福平外排系统,这使得agr突变生物膜对利福平的耐药性比其他抗生素更低,而不是更强。我们的研究为使用利福平治疗葡萄球菌生物膜感染提供了科学依据,并强调了了解感染过程中基因适应对生物膜疗法的使用和发展的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Export by a quorum sensing–controlled drug exporter underlies rifampicin’s strong activity against staphylococcal biofilms
Biofilm infections on indwelling medical devices are a major cause of health care–associated infection and mortality. Most of these infections are caused by staphylococci. Biofilm formation presents a continued clinical challenge because of the association with dramatically increased nonspecific antimicrobial resistance. Unlike most antibiotics, rifampicin is active against staphylococcal biofilm infections; however, the mechanism is unknown. Using in vitro assays and mouse models of biofilm infection, we show here that rifampicin is more effective than other antibiotics against staphylococcal agr mutants, which are linked to serious biofilm infections because they produce extended biofilms. We found that this superiority results from an Agr-controlled rifampicin efflux system, which makes agr mutant biofilms less resistant to rifampicin, rather than more resistant, than they are to other antibiotics. Our study provides a scientific rationale supporting the use of rifampicin in staphylococcal biofilm infections and emphasizes the importance of understanding genetic adaptations during infection for the use and development of biofilm therapeutics.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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