The anti-inflammatory drugs diclofenac and ketorolac inhibit urease activity and biofilm formation by uropathogenic Proteus mirabilis.

IF 3.1 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Afaf Eladl, Hisham A Abbas, Samar S Elbaramawi, Marwa Ibrahim Abd El-Hamid, Shaimaa I Nazeih
{"title":"The anti-inflammatory drugs diclofenac and ketorolac inhibit urease activity and biofilm formation by uropathogenic Proteus mirabilis.","authors":"Afaf Eladl, Hisham A Abbas, Samar S Elbaramawi, Marwa Ibrahim Abd El-Hamid, Shaimaa I Nazeih","doi":"10.1007/s12223-025-01336-7","DOIUrl":null,"url":null,"abstract":"<p><p>Proteus mirabilis is a major bacterium responsible for catheter-associated urinary tract infections (CAUTIs). Urease enzyme has a great role in the pathogenesis of Proteus mirabilis. Using urease, Proteus mirabilis can decompose urea to produce ammonia that increases urine pH and enhances crystal precipitation and crystalline biofilm formation. This leads to catheter blockage and pyelonephritis, respectively. Urease inhibitors are of great value in controlling this problem. Diclofenac sodium and ketorolac tromethamine, with their metal chelating activities, can inactivate urease by chelation of nickel ion in the active site of urease. This study investigated the ability of diclofenac sodium and ketorolac tromethamine to inhibit urease activity in Proteus mirabilis and crystalline biofilm formation. Diclofenac sodium and ketorolac tromethamine showed comparable activities against urease in cell lysates and whole cultures, with subsequent inhibition of pH increase and crystal formation in artificial urine. Diclofenac sodium showed higher biofilm inhibition and downregulation of urease genes ureR and ureC in RT-qPCR. The docking study showed the ability of both drugs to bind to urease enzyme and to chelate nickel ions in the active site of urease, suggesting that nickel chelation is the mode of inhibition of urease enzyme. In conclusion, diclofenac sodium and ketorolac tromethamine are two urease inhibitors that may be useful in treating Proteus mirabilis CAUTI.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Folia microbiologica","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12223-025-01336-7","RegionNum":4,"RegionCategory":"生物学","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

Proteus mirabilis is a major bacterium responsible for catheter-associated urinary tract infections (CAUTIs). Urease enzyme has a great role in the pathogenesis of Proteus mirabilis. Using urease, Proteus mirabilis can decompose urea to produce ammonia that increases urine pH and enhances crystal precipitation and crystalline biofilm formation. This leads to catheter blockage and pyelonephritis, respectively. Urease inhibitors are of great value in controlling this problem. Diclofenac sodium and ketorolac tromethamine, with their metal chelating activities, can inactivate urease by chelation of nickel ion in the active site of urease. This study investigated the ability of diclofenac sodium and ketorolac tromethamine to inhibit urease activity in Proteus mirabilis and crystalline biofilm formation. Diclofenac sodium and ketorolac tromethamine showed comparable activities against urease in cell lysates and whole cultures, with subsequent inhibition of pH increase and crystal formation in artificial urine. Diclofenac sodium showed higher biofilm inhibition and downregulation of urease genes ureR and ureC in RT-qPCR. The docking study showed the ability of both drugs to bind to urease enzyme and to chelate nickel ions in the active site of urease, suggesting that nickel chelation is the mode of inhibition of urease enzyme. In conclusion, diclofenac sodium and ketorolac tromethamine are two urease inhibitors that may be useful in treating Proteus mirabilis CAUTI.

抗炎药双氯芬酸和酮咯酸抑制尿路致病性变形杆菌脲酶活性和生物膜的形成。
变形杆菌是引起导尿管相关性尿路感染(CAUTIs)的主要细菌。脲酶在变形杆菌的发病过程中起重要作用。变形杆菌利用脲酶分解尿素生成氨,提高尿液pH值,促进结晶沉淀和结晶生物膜的形成。这分别导致导管堵塞和肾盂肾炎。脲酶抑制剂在控制这一问题上具有重要的价值。双氯芬酸钠和酮咯酸三聚氰胺具有金属螯合活性,可通过螯合脲酶活性部位的镍离子使脲酶失活。本研究考察了双氯芬酸钠和酮咯酸三聚氰胺对变形杆菌脲酶活性和结晶生物膜形成的抑制作用。双氯芬酸钠和酮酸丙二胺在细胞裂解物和全培养物中对脲酶具有相当的抑制活性,随后在人工尿液中抑制pH升高和晶体形成。RT-qPCR结果显示双氯芬酸钠对脲酶基因ureR和ureC具有较高的生物膜抑制和下调作用。对接研究表明,两种药物均能与脲酶结合,并在脲酶活性位点螯合镍离子,提示镍螯合是抑制脲酶的方式。综上所述,双氯芬酸钠和酮咯酸tromethamine是两种脲酶抑制剂,可能对治疗奇异变形杆菌CAUTI有效。
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
Folia microbiologica
Folia microbiologica 工程技术-生物工程与应用微生物
CiteScore
5.80
自引率
0.00%
发文量
82
审稿时长
6-12 weeks
期刊介绍: Unlike journals which specialize ever more narrowly, Folia Microbiologica (FM) takes an open approach that spans general, soil, medical and industrial microbiology, plus some branches of immunology. This English-language journal publishes original papers, reviews and mini-reviews, short communications and book reviews. The coverage includes cutting-edge methods and promising new topics, as well as studies using established methods that exhibit promise in practical applications such as medicine, animal husbandry and more. The coverage of FM is expanding beyond Central and Eastern Europe, with a growing proportion of its contents contributed by international authors.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信