Department of Chemical and Biological Engineering, The Hong Kong University of Science & Technology, Kowloon, Hong Kong, People's Republic of China.
Department of Ocean Science and Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, The Hong Kong University of Science & Technology, Kowloon, Hong Kong, People's Republic of China.
Microbiol Spectr. 2022 Feb 23;10(1):e0232021. doi: 10.1128/spectrum.02320-21.
Elasnin is a recently reported antibiofilm agent that is effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, we observed that elasnin has a superior activity in eradicating daptomycin-resistant MRSA strain biofilm, with a lower minimum biofilm eradication concentration (MBEC) value of 0.625 μg/mL, compared to 2.5 μg/mL for the wild type. Confocal microscopy further confirmed the higher biofilm eradication on the daptomycin-resistant strain, displaying ∼53% decrease in cell density upon elasnin treatment, while the wild-type strain was only decreased by ∼15%. Quantitative proteomics revealed that the daptomycin-resistant strain has a lower expression of the membrane, cell wall, and extracellular proteins, and also proteins involved in the arginine biosynthesis, pathogenesis, and cell adhesion compared to the wild type, which may result in weaker biofilm development. This study highlights the potential clinical application of elasnin through its superior biofilm eradication activity against a daptomycin-resistant MRSA strain, and revealed the associated processes governing this superior activity through proteomics analysis. Due to the increased use of daptomycin for the treatment of MRSA infections, the emergence of daptomycin-resistant strains has become prevalent in recent years. In this study, we discovered that elasnin, a newly reported antibiofilm compound, has a superior activity in eradicating daptomycin-resistant MRSA strain biofilms compared to the wild type. Follow-up analysis revealed the reason behind this superior activity, which is the lower expression of key proteins that play a role in pathogenesis and cell adhesion in the daptomycin-resistant strain, leading to weaker biofilm development. This showcases the potential use of elasnin in clinical settings where daptomycin-resistant strains and biofilm formation are prevalent. Altogether, our study provides new insights into the mechanism of elasnin in MRSA biofilm cells and identified its superior biofilm eradicating activity in the daptomycin-resistant strain.
埃拉西林是一种最近报道的抗生物膜剂，对包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的革兰氏阳性菌有效。值得注意的是，我们观察到埃拉西林在消除达托霉素耐药 MRSA 菌株生物膜方面具有更高的活性，其最低生物膜清除浓度（MBEC）值为 0.625μg/mL，而野生型的 MBEC 值为 2.5μg/mL。共聚焦显微镜进一步证实了埃拉西林对达托霉素耐药菌株的更高生物膜清除率，显示出埃拉西林处理后细胞密度降低了约 53%，而野生型菌株仅降低了约 15%。定量蛋白质组学揭示，与野生型相比，达托霉素耐药菌株的膜、细胞壁和细胞外蛋白以及精氨酸生物合成、发病机制和细胞黏附相关蛋白的表达水平较低，这可能导致生物膜形成能力较弱。这项研究通过其对达托霉素耐药 MRSA 菌株的优越生物膜清除活性强调了埃拉西林的潜在临床应用，并通过蛋白质组学分析揭示了与这种优越活性相关的过程。由于达托霉素在治疗 MRSA 感染中的广泛应用，近年来达托霉素耐药菌株的出现变得普遍。在这项研究中，我们发现一种新报道的抗生物膜化合物埃拉西林在消除达托霉素耐药 MRSA 菌株生物膜方面比野生型更有效。后续分析揭示了这种优越活性的原因，即达托霉素耐药菌株中参与发病机制和细胞黏附的关键蛋白表达水平较低，导致生物膜形成能力较弱。这展示了埃拉西林在达托霉素耐药菌株和生物膜形成普遍存在的临床环境中的潜在用途。总之，我们的研究提供了埃拉西林在 MRSA 生物膜细胞中的作用机制的新见解，并确定了其在达托霉素耐药菌株中的优越生物膜清除活性。
