Potential of recombinant CAV1-Fc in the treatment of ApxI toxin-induced damage by Actinobacillus pleuropneumoniae

IF 2.4 2区 农林科学 Q3 MICROBIOLOGY
Yaofang Hu , Mengdi Zhang , Gan Yang , Haoran Guo , Changsheng Jiang , Pei Zhou , Yanhong Chen , Mengjia Zhang , Ahmed H. Ghonaim , Wentao Li , Qigai He
{"title":"Potential of recombinant CAV1-Fc in the treatment of ApxI toxin-induced damage by Actinobacillus pleuropneumoniae","authors":"Yaofang Hu ,&nbsp;Mengdi Zhang ,&nbsp;Gan Yang ,&nbsp;Haoran Guo ,&nbsp;Changsheng Jiang ,&nbsp;Pei Zhou ,&nbsp;Yanhong Chen ,&nbsp;Mengjia Zhang ,&nbsp;Ahmed H. Ghonaim ,&nbsp;Wentao Li ,&nbsp;Qigai He","doi":"10.1016/j.vetmic.2025.110504","DOIUrl":null,"url":null,"abstract":"<div><div>Currently, porcine contagious pleuropneumonia (PCP) caused by <em>Actinobacillus pleuropneumoniae</em> (APP), poses a significant threat to the pig breeding industry. There is an urgent need for effective therapeutic and prophylactic treatments, especially those that can overcome the limitations associated with vaccines and antibiotics. This includes the development of novel antitoxin agents, immunomodulatory therapies, and alternative strategies like phage therapy and herbal extracts. Our previous study has demonstrated membrane protein caveolin-1 (CAV1) is a key protein that acts as a functional receptor of APP ApxI toxin by binding to its acylated region. Here, we developed recombinant human N-CAV1-Fc fusion protein and C-CAV1-Fc fusion protein. Both fusion proteins could tightly bind to ApxI toxin. N-CAV1-Fc and C-CAV1-Fc fusion proteins efficiently blocked the interaction between ApxI toxin and immortalized porcine alveolar macrophages (iPAMs), thereby inhibiting cell apoptosis caused by APP ApxI toxin. Furthermore, prophylactic and therapeutic CAV1-Fc treatments effectively protected mice from ApxI toxin-induced damage, as determined by reduced weight loss, apoptosis factor transcription, and pathological changes in the lungs. The protective effects of N-CAV1-Fc and C-CAV1-Fc showed clear dose-dependent efficacy <em>in vivo</em>. Protein kinetics data indicated that N-CAV1-Fc has a relatively longer half-life <em>in vivo</em> compared to C-CAV1-Fc, making it an excellent candidate for prevention and treatment of APP infections.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110504"},"PeriodicalIF":2.4000,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary microbiology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378113525001397","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Currently, porcine contagious pleuropneumonia (PCP) caused by Actinobacillus pleuropneumoniae (APP), poses a significant threat to the pig breeding industry. There is an urgent need for effective therapeutic and prophylactic treatments, especially those that can overcome the limitations associated with vaccines and antibiotics. This includes the development of novel antitoxin agents, immunomodulatory therapies, and alternative strategies like phage therapy and herbal extracts. Our previous study has demonstrated membrane protein caveolin-1 (CAV1) is a key protein that acts as a functional receptor of APP ApxI toxin by binding to its acylated region. Here, we developed recombinant human N-CAV1-Fc fusion protein and C-CAV1-Fc fusion protein. Both fusion proteins could tightly bind to ApxI toxin. N-CAV1-Fc and C-CAV1-Fc fusion proteins efficiently blocked the interaction between ApxI toxin and immortalized porcine alveolar macrophages (iPAMs), thereby inhibiting cell apoptosis caused by APP ApxI toxin. Furthermore, prophylactic and therapeutic CAV1-Fc treatments effectively protected mice from ApxI toxin-induced damage, as determined by reduced weight loss, apoptosis factor transcription, and pathological changes in the lungs. The protective effects of N-CAV1-Fc and C-CAV1-Fc showed clear dose-dependent efficacy in vivo. Protein kinetics data indicated that N-CAV1-Fc has a relatively longer half-life in vivo compared to C-CAV1-Fc, making it an excellent candidate for prevention and treatment of APP infections.
求助全文
约1分钟内获得全文 求助全文
来源期刊
Veterinary microbiology
Veterinary microbiology 农林科学-兽医学
CiteScore
5.90
自引率
6.10%
发文量
221
审稿时长
52 days
期刊介绍: Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.
×
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:481959085
Book学术官方微信