The importance role of central proline to the antimicrobial potency and selectivity of indolicidin

IF 2.3 3区生物学 Q3 MICROBIOLOGY

Archives of Microbiology Pub Date : 2025-03-20 DOI:10.1007/s00203-025-04299-y

Hang Ngo Thu, Hoa Ngo Van, Hai Bui Thi Phuong, Thinh Pham Duc, Khanh Hoang Van, Khoa Nguyen Vu, Tan Nguyen Van, Linh Dang Thuy, Le Minh Bui, Tung Truong Thanh, Huy Luong Xuan, Mao Can Van

{"title":"The importance role of central proline to the antimicrobial potency and selectivity of indolicidin","authors":"Hang Ngo Thu, Hoa Ngo Van, Hai Bui Thi Phuong, Thinh Pham Duc, Khanh Hoang Van, Khoa Nguyen Vu, Tan Nguyen Van, Linh Dang Thuy, Le Minh Bui, Tung Truong Thanh, Huy Luong Xuan, Mao Can Van","doi":"10.1007/s00203-025-04299-y","DOIUrl":null,"url":null,"abstract":"<div>The increasing prevalence of multidrug-resistant pathogens urged the development of new therapeutic strategies, and antimicrobial peptides (AMPs) have emerged as promising candidates. Indolicidin, a proline-rich AMP, is effective against a wide range of pathogens by penetrating the membrane to disrupt the cytoplasmic membrane or inhibit DNA synthesis. This study investigates the impact of replacing the central proline residue in Indolicidin with glycine (IND-7G), D-proline (IND-7DP), or lysine (IND-7K). Results show that both glycine and D-proline substitutions significantly reduced antimicrobial activity with lower hemolysis than the parent peptide. Besides, the analog having lysine substitution (IND-7K) slightly increased activity against E. coli and C. albicans but reduced potency against S. aureus, E. faecalis, and K. pneumoniae. The hemolytic activity of IND-7K remained comparable to that of Indolicidin. These findings demonstrated the essential role of proline in maintaining the antimicrobial efficacy of Indolicidin.</div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"207 4","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Microbiology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s00203-025-04299-y","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The increasing prevalence of multidrug-resistant pathogens urged the development of new therapeutic strategies, and antimicrobial peptides (AMPs) have emerged as promising candidates. Indolicidin, a proline-rich AMP, is effective against a wide range of pathogens by penetrating the membrane to disrupt the cytoplasmic membrane or inhibit DNA synthesis. This study investigates the impact of replacing the central proline residue in Indolicidin with glycine (IND-7G), D-proline (IND-7DP), or lysine (IND-7K). Results show that both glycine and D-proline substitutions significantly reduced antimicrobial activity with lower hemolysis than the parent peptide. Besides, the analog having lysine substitution (IND-7K) slightly increased activity against E. coli and C. albicans but reduced potency against S. aureus, E. faecalis, and K. pneumoniae. The hemolytic activity of IND-7K remained comparable to that of Indolicidin. These findings demonstrated the essential role of proline in maintaining the antimicrobial efficacy of Indolicidin.

Abstract Image

查看原文本刊更多论文

中心脯氨酸对吲哚啶抗菌效力和选择性的重要作用

耐多药病原体的日益流行促使人们开发新的治疗策略，而抗菌肽（AMPs）已成为前景广阔的候选药物。吲哚啶是一种富含脯氨酸的 AMP，能穿透细胞膜破坏细胞质膜或抑制 DNA 合成，对多种病原体有效。本研究探讨了用甘氨酸（IND-7G）、D-脯氨酸（IND-7DP）或赖氨酸（IND-7K）取代吲哚啶中的中心脯氨酸残基的影响。结果表明，与母肽相比，甘氨酸和 D-脯氨酸的取代都能显著降低抗菌活性和溶血率。此外，取代赖氨酸的类似物（IND-7K）对大肠杆菌和白僵菌的活性略有提高，但对金黄色葡萄球菌、粪大肠杆菌和肺炎双球菌的活性却有所降低。IND-7K 的溶血活性仍与吲哚啶相当。这些研究结果表明，脯氨酸在维持吲哚啶的抗菌功效方面起着至关重要的作用。

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

Archives of Microbiology 生物-微生物学

CiteScore

4.90

自引率

3.60%

发文量

601

审稿时长

3 months

期刊介绍： Research papers must make a significant and original contribution to microbiology and be of interest to a broad readership. The results of any experimental approach that meets these objectives are welcome, particularly biochemical, molecular genetic, physiological, and/or physical investigations into microbial cells and their interactions with their environments, including their eukaryotic hosts. Mini-reviews in areas of special topical interest and papers on medical microbiology, ecology and systematics, including description of novel taxa, are also published. Theoretical papers and those that report on the analysis or ''mining'' of data are acceptable in principle if new information, interpretations, or hypotheses emerge.