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对抗耐甲氧西林的方法:用抑制剂肽靶向RelP蛋白以减轻耐药性。

Approach to Combat Methicillin-resistant : Targeting RelP Protein with Inhibitor Peptide to Mitigate Drug Resistance.

作者信息

Sinoliya Priyanka, Solanki Pooran Singh, Niraj Ravi Ranjan Kumar, Sharma Vinay

机构信息

Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India.

Birla Institute of Technology, Mesra, India.

出版信息

Curr Drug Discov Technol. 2025;22(4):e15701638337060. doi: 10.2174/0115701638337060250121154347.

DOI:10.2174/0115701638337060250121154347
PMID:39949095
Abstract

INTRODUCTION

Methicillin-resistant (MRSA), known for its resistance to multiple antibiotics, has emerged as a major global health concern. It facilitates biofilm formation under stressful conditions by catalyzing the synthesis of alarmones (p)ppGpp and ppGpp. These alarmones on accumulation lead to biofilm formation and cause resistance towards antibiotics.

METHODS

This condition has prompted the exploration of various novel approaches and methodologies to combat MRSA infections. Among these, peptide therapeutics stand out as a promising nextgeneration treatment option. In this study, ninety antimicrobial peptides were sourced from the antimicrobial peptide database and the other sixty-one peptide sequences were designed using the Pepdraw server. These peptide sequences were screened out using different tools. The proteinpeptide molecular interaction was studied using a molecular docking and molecular dynamic simulation technique.

RESULTS AND DISCUSSION

Out of 151 peptide sequences, Pantocin wh-1 emerged as the most promising drug candidate. Both molecular interaction studies and molecular dynamics simulations demonstrated positive results.

CONCLUSION

Peptide therapeutics is a novel approach researchers are presently exploring as it provides prompt significant results and promotes a new insight towards dealing with conditions like MDR. Pantocin wh-1 is a peptide drug currently listed as an accessible anti-tuberculosis peptide, and this study suggests the repurposing of this drug as a viable treatment option for MRSA infections.

摘要

引言

耐甲氧西林金黄色葡萄球菌(MRSA)以其对多种抗生素的耐药性而闻名,已成为全球主要的健康问题。它通过催化警报素(p)ppGpp和ppGpp的合成,在应激条件下促进生物膜形成。这些警报素积累后会导致生物膜形成并对抗生素产生耐药性。

方法

这种情况促使人们探索各种新颖的方法和技术来对抗MRSA感染。其中,肽疗法作为一种有前途的下一代治疗选择脱颖而出。在本研究中,90种抗菌肽来自抗菌肽数据库,另外61种肽序列使用Pepdraw服务器设计。这些肽序列使用不同工具进行筛选。使用分子对接和分子动力学模拟技术研究蛋白质 - 肽分子相互作用。

结果与讨论

在151种肽序列中,Pantocin wh - 1成为最有前途的候选药物。分子相互作用研究和分子动力学模拟均显示出积极结果。

结论

肽疗法是研究人员目前正在探索的一种新方法,因为它能迅速产生显著效果,并为应对多药耐药等情况提供新的见解。Pantocin wh - 1是一种目前列为可获得的抗结核肽的肽类药物,本研究表明将该药物重新用作MRSA感染的可行治疗选择。

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本文引用的文献

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Differentiating stable and unstable protein using convolution neural network and molecular dynamics simulations.利用卷积神经网络和分子动力学模拟区分稳定和不稳定的蛋白质。
Comput Biol Chem. 2024 Jun;110:108081. doi: 10.1016/j.compbiolchem.2024.108081. Epub 2024 Apr 20.
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Differences in Biofilm Formation by Methicillin-Resistant and Methicillin-Susceptible Strains.耐甲氧西林菌株与甲氧西林敏感菌株在生物膜形成方面的差异。
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Bacteriophage Therapy for Infections: A Review of Animal Models, Treatments, and Clinical Trials.噬菌体疗法治疗感染:动物模型、治疗方法和临床试验综述。
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Incidence of biofilm formation among MRSA and MSSA clinical isolates from hospitalized patients in Israel.以色列住院患者中耐甲氧西林金黄色葡萄球菌和甲氧西林敏感金黄色葡萄球菌临床分离株生物膜形成的发生率。
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