Antimicrobial activity of α/β hybrid peptides incorporating tBu-β3,3Ac6c against methicillin-resistant Staphylococcus aureus

IF 2.1 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Antibiotics Pub Date : 2024-10-29 DOI:10.1038/s41429-024-00773-9

Aminur Rahman Sarkar, Jyoti Kumari, Arti Rathore, Rubina Chowdhary, Rakshit Manhas, Shifa Firdous, Avisek Mahapa, Rajkishor Rai

{"title":"Antimicrobial activity of α/β hybrid peptides incorporating tBu-β3,3Ac6c against methicillin-resistant Staphylococcus aureus","authors":"Aminur Rahman Sarkar, Jyoti Kumari, Arti Rathore, Rubina Chowdhary, Rakshit Manhas, Shifa Firdous, Avisek Mahapa, Rajkishor Rai","doi":"10.1038/s41429-024-00773-9","DOIUrl":null,"url":null,"abstract":"The incorporation of β-amino acids into peptides is a promising approach to develop proteolytically stable therapeutic agents. Short α/β hybrid peptides containing tBu-β3,3Ac6cː H2N-Lys-tBu-β3,3Ac6c-PEA, P1; H2N-Orn-tBu-β3,3Ac6c-PEA, P2; H2N-Arg-tBu-β3,3Ac6c-PEA, P3; LA-Lys-tBu-β3,3Ac6c-PEA, P4; LA-Orn-tBu-β3,3Ac6c-PEA, P5; LA-Arg-tBu-β3,3Ac6c-PEA, P6; LAu-Lys-tBu-β3,3Ac6c-PEA, P7; LAu-Orn-tBu-β3,3Ac6c-PEA, P8; and LAu-Arg-tBu-β3,3Ac6c-PEA, P9 were prepared. The antimicrobial efficacies of all the peptides were evaluated against ESKAPE pathogens, along with a small panel of multi-drug resistant (MDR) clinical isolates of S. aureus. Among all the peptides, P4, P6, and P7 showed significant efficacies against P. aeruginosa, S. aureus, and MRSA with an MIC value ranging from 6.25 to 12.5 μM. Further, in vitro, anti-staphylococcal assessment with their antimicrobial synergy of the peptides P4, P6, and P7 was carried out against MRSA, due to its better efficacy. The peptides P6 and P7 exhibited MRSA biofilm inhibition of 70% and 77%, respectively, at 4×MIC concentration. At its MIC concentration, about 19% hemolysis was observed for P4, P6, and P7.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 12","pages":"794-801"},"PeriodicalIF":2.1000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Antibiotics","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41429-024-00773-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The incorporation of β-amino acids into peptides is a promising approach to develop proteolytically stable therapeutic agents. Short α/β hybrid peptides containing tBu-β3,3Ac6cː H2N-Lys-tBu-β3,3Ac6c-PEA, P1; H2N-Orn-tBu-β3,3Ac6c-PEA, P2; H2N-Arg-tBu-β3,3Ac6c-PEA, P3; LA-Lys-tBu-β3,3Ac6c-PEA, P4; LA-Orn-tBu-β3,3Ac6c-PEA, P5; LA-Arg-tBu-β3,3Ac6c-PEA, P6; LAu-Lys-tBu-β3,3Ac6c-PEA, P7; LAu-Orn-tBu-β3,3Ac6c-PEA, P8; and LAu-Arg-tBu-β3,3Ac6c-PEA, P9 were prepared. The antimicrobial efficacies of all the peptides were evaluated against ESKAPE pathogens, along with a small panel of multi-drug resistant (MDR) clinical isolates of S. aureus. Among all the peptides, P4, P6, and P7 showed significant efficacies against P. aeruginosa, S. aureus, and MRSA with an MIC value ranging from 6.25 to 12.5 μM. Further, in vitro, anti-staphylococcal assessment with their antimicrobial synergy of the peptides P4, P6, and P7 was carried out against MRSA, due to its better efficacy. The peptides P6 and P7 exhibited MRSA biofilm inhibition of 70% and 77%, respectively, at 4×MIC concentration. At its MIC concentration, about 19% hemolysis was observed for P4, P6, and P7.

Abstract Image

查看原文本刊更多论文

含有 tBu-β3,3Ac6c 的 α/β 杂交肽对耐甲氧西林金黄色葡萄球菌的抗菌活性。

在肽中加入β-氨基酸是开发蛋白水解稳定的治疗药物的一种很有前景的方法。含有 tBu-β3,3Ac6cː H2N-Lys-tBu-β3,3Ac6c-PEA 的短 α/β 杂交肽，P1；H2N-Orn-tBu-β3,3Ac6c-PEA，P2；H2N-Arg-tBu-β3,3Ac6c-PEA，P3；LA-Lys-tBu-β3,3Ac6c-PEA，P4；LAu-Orn-tBu-β3,3Ac6c-PEA，P5；LA-Arg-tBu-β3,3Ac6c-PEA，P6；LAu-Lys-tBu-β3,3Ac6c-PEA，P7；LAu-Orn-tBu-β3,3Ac6c-PEA，P8；LAu-Arg-tBu-β3,3Ac6c-PEA，P9。评估了所有肽类对 ESKAPE 病原体以及一小批耐多药（MDR）金黄色葡萄球菌临床分离株的抗菌效果。在所有肽中，P4、P6 和 P7 对铜绿假单胞菌、金黄色葡萄球菌和 MRSA 有显著疗效，MIC 值在 6.25 到 12.5 μM 之间。此外，由于多肽 P4、P6 和 P7 对 MRSA 具有更好的疗效，因此对它们的抗葡萄球菌协同作用进行了体外评估。在 4 倍 MIC 浓度下，多肽 P6 和 P7 对 MRSA 生物膜的抑制率分别为 70% 和 77%。在其 MIC 浓度下，P4、P6 和 P7 的溶血率约为 19%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Antibiotics 医学-免疫学

CiteScore

6.60

自引率

3.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Antibiotics seeks to promote research on antibiotics and related types of biologically active substances and publishes Articles, Review Articles, Brief Communication, Correspondence and other specially commissioned reports. The Journal of Antibiotics accepts papers on biochemical, chemical, microbiological and pharmacological studies. However, studies regarding human therapy do not fall under the journal’s scope. Contributions regarding recently discovered antibiotics and biologically active microbial products are particularly encouraged. Topics of particular interest within the journal''s scope include, but are not limited to, those listed below: Discovery of new antibiotics and related types of biologically active substances Production, isolation, characterization, structural elucidation, chemical synthesis and derivatization, biological activities, mechanisms of action, and structure-activity relationships of antibiotics and related types of biologically active substances Biosynthesis, bioconversion, taxonomy and genetic studies on producing microorganisms, as well as improvement of production of antibiotics and related types of biologically active substances Novel physical, chemical, biochemical, microbiological or pharmacological methods for detection, assay, determination, structural elucidation and evaluation of antibiotics and related types of biologically active substances Newly found properties, mechanisms of action and resistance-development of antibiotics and related types of biologically active substances.