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Bromophenazine derivatives with potent inhibition, dispersion and eradication activities against Staphylococcus aureus biofilms

机译：具有对金黄色葡萄球菌生物膜的有效抑制，分散和根除活性的溴吩嗪衍生物

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摘要

Bacterial biofilms are surface-attached communities of bacteria that are: (1) highly prevalent in human infections, and (2) resistant to conventional antibiotic treatments and host immune responses. It has only been in the last similar to 20 years that bacterial biofilms have been identified as a critical biomedical hurdle in infectious disease and human health. Staphylococcus aureus is a leading cause of nosocomial and community-acquired infections and is notorious for its ability to form drug-resistant biofilms. Despite the need for antibacterial agents that target S. aureus biofilms, few chemical scaffolds are known that are capable of inhibiting, dispersing or eradicating their biofilms. Here, we report the discovery of bromophenazine derivatives that display antibiofilm activities as either potent biofilm inhibitors (IC50 values 0.55-10.3 mu M) or dispersal agents (EC50 values 1.4-29.3 mu M) and biofilm eradicators (MBEC values 100-200 mu M) against S. aureus strains, including a methicillin-resistant Staphylococcus aureus clinical isolate. These discoveries could lead to the development of new treatment options that target drug-resistant, biofilm-associated S. aureus infections.
机译：细菌生物膜是细菌的表面附着群落，它们是：（1）在人类感染中高度流行，以及（2）对常规抗生素治疗和宿主免疫反应具有抗性。直到近20年来，细菌生物膜才被确定为传染病和人类健康的关键生物医学障碍。金黄色葡萄球菌是医院和社区获得性感染的主要原因，并且以其形成抗药性生物膜的能力而臭名昭著。尽管需要靶向金黄色葡萄球菌生物膜的抗菌剂，但是已知很少有能够抑制，分散或消除其生物膜的化学支架。在这里，我们报告发现具有抗生物膜活性的溴吩嗪衍生物作为有效的生物膜抑制剂（IC50值为0.55-10.3μM）或分散剂（EC50值为1.4-29.3μM）和生物膜消除剂（MBEC值为100-200μM ）对抗金黄色葡萄球菌菌株，包括耐甲氧西林的金黄色葡萄球菌临床分离株。这些发现可能会导致针对耐药性，与生物膜相关的金黄色葡萄球菌感染的新治疗方法的开发。

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