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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Artesunate has its enhancement on antibacterial activity of β-lactams via increasing the antibiotic accumulation within methicillin-resistant Staphylococcus aureus (MRSA)
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Artesunate has its enhancement on antibacterial activity of β-lactams via increasing the antibiotic accumulation within methicillin-resistant Staphylococcus aureus (MRSA)

机译:青蒿琥酯通过增加耐甲氧西林的金黄色葡萄球菌(MRSA)中的抗生素积累而增强了β-内酰胺的抗菌活性

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摘要

Methicillin-resistant Staphylococcus aureus (MRSA) has now emerged as a predominant and serious pathogen because of its resistance to a large group of antibiotics, leading to high morbidity and mortality. Therefore, to develop new agents against resistance is urgently required. Previously, artesunate (AS) was found to enhance the antibacterial effect of β-lactams against MRSA. In this study, AS was first found to increase the accumulation of antibiotics (daunorubicin and oxacillin) within MRSA by laser confocal microscopy and liquid chromatography-tandem MS method, suggesting the increased antibiotics accumulation might be related to the enhancement of AS on antibiotics. Furthermore, AS was found not to destroy the cell structure of MRSA by transmission electron microscope. AS was found to inhibit gene expressions of important efflux pumps such as NorA, NorB and NorC, but not MepA, SepA and MdeA. In conclusion, our results showed that AS was capable of enhancing the antibacterial activity of β-lactams via increasing antibiotic accumulations within MRSA through inhibiting gene expressions of efflux pumps such as NorA, NorB and NorC, but did not destroy the cell structure of MRSA. AS could be further investigated as a candidate drug for treatment of MRSA infection.
机译:耐甲氧西林的金黄色葡萄球菌(MRSA)已成为主要和严重的病原体,因为它对大量抗生素具有耐药性,从而导致较高的发病率和死亡率。因此,迫切需要开发新的抗药性药物。以前,青蒿琥酯(AS)被发现可以增强β-内酰胺类对MRSA的抗菌作用。在这项研究中,首先通过激光共聚焦显微镜和液相色谱-串联质谱法首次发现AS增加了MRSA中的抗生素(柔红霉素和奥沙西林)积累,这表明增加的抗生素积累可能与AS对抗生素的增强有关。此外,通过透射电子显微镜发现AS不会破坏MRSA的细胞结构。发现AS抑制重要外排泵的基因表达,例如NorA,NorB和NorC,但不抑制MepA,SepA和MdeA。总之,我们的结果表明,AS能够通过抑制外排泵的基因表达(例如NorA,NorB和NorC),通过增加MRSA中的抗生素积累来增强β-内酰胺的抗菌活性,但不会破坏MRSA的细胞结构。 AS可以作为治疗MRSA感染的候选药物进行进一步研究。

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