Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter.

IF 2.5 3区 工程技术 Q2 BIOLOGY
Yale Journal of Biology and Medicine Pub Date : 2022-12-01
Franziska Winzig, Shiv Gandhi, Alina Lee, Silvia Würstle, Gail L Stanley, Isabella Capuano, Isabel Neuringer, Jonathan L Koff, Paul E Turner, Benjamin K Chan
{"title":"Inhaled Bacteriophage Therapy for Multi-Drug Resistant <i>Achromobacter</i>.","authors":"Franziska Winzig,&nbsp;Shiv Gandhi,&nbsp;Alina Lee,&nbsp;Silvia Würstle,&nbsp;Gail L Stanley,&nbsp;Isabella Capuano,&nbsp;Isabel Neuringer,&nbsp;Jonathan L Koff,&nbsp;Paul E Turner,&nbsp;Benjamin K Chan","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The rise of antimicrobial resistant (AMR) bacteria is a global public health threat. AMR <i>Achromobacter</i> bacteria pose a challenging clinical problem, particularly for those with cystic fibrosis (CF) who are predisposed to chronic bacterial lung infections. Lytic bacteriophages (phages) offer a potential alternative to treat AMR infections, with the possible benefit that phage selection for resistance in target bacteria might coincide with reduced pathogenicity. The result is a genetic \"trade-off,\" such as increased sensitivity to chemical antibiotics, and/or decreased virulence of surviving bacteria that are phage resistant. Here, we show that two newly discovered lytic phages against <i>Achromobacter</i> were associated with stabilization of respiratory status when deployed to treat a chronic pulmonary infection in a CF patient using inhaled (nebulized) phage therapy. The two phages demonstrate traits that could be generally useful in their development as therapeutics, especially the possibility that the phages can select for clinically useful trade-offs if bacteria evolve phage resistance following therapy. We discuss the limitations of the current study and suggest further work that should explore whether the phages could be generally useful in targeting pulmonary or other <i>Achromobacter</i> infections in CF patients.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"95 4","pages":"413-427"},"PeriodicalIF":2.5000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8e/57/yjbm_95_4_413.PMC9765334.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Yale Journal of Biology and Medicine","FirstCategoryId":"5","ListUrlMain":"","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The rise of antimicrobial resistant (AMR) bacteria is a global public health threat. AMR Achromobacter bacteria pose a challenging clinical problem, particularly for those with cystic fibrosis (CF) who are predisposed to chronic bacterial lung infections. Lytic bacteriophages (phages) offer a potential alternative to treat AMR infections, with the possible benefit that phage selection for resistance in target bacteria might coincide with reduced pathogenicity. The result is a genetic "trade-off," such as increased sensitivity to chemical antibiotics, and/or decreased virulence of surviving bacteria that are phage resistant. Here, we show that two newly discovered lytic phages against Achromobacter were associated with stabilization of respiratory status when deployed to treat a chronic pulmonary infection in a CF patient using inhaled (nebulized) phage therapy. The two phages demonstrate traits that could be generally useful in their development as therapeutics, especially the possibility that the phages can select for clinically useful trade-offs if bacteria evolve phage resistance following therapy. We discuss the limitations of the current study and suggest further work that should explore whether the phages could be generally useful in targeting pulmonary or other Achromobacter infections in CF patients.

Abstract Image

Abstract Image

Abstract Image

吸入噬菌体治疗多重耐药无色杆菌。
抗微生物药物耐药性(AMR)细菌的增加对全球公共卫生构成威胁。AMR无色杆菌构成了一个具有挑战性的临床问题,特别是对于那些易患慢性细菌性肺部感染的囊性纤维化(CF)患者。裂解噬菌体(噬菌体)提供了一种治疗抗菌素耐药性感染的潜在替代方案,其可能的好处是,在目标细菌中选择耐药的噬菌体可能与降低致病性相一致。结果是一种遗传“权衡”,例如对化学抗生素的敏感性增加,和/或对噬菌体耐药的存活细菌的毒力降低。在这里,我们表明,当使用吸入(雾化)噬菌体治疗CF患者的慢性肺部感染时,两种新发现的抗无色杆菌的裂解噬菌体与呼吸状态的稳定有关。这两种噬菌体表现出的特性可能在它们作为治疗药物的发展中普遍有用,特别是如果细菌在治疗后进化出噬菌体耐药性,噬菌体可以选择临床上有用的权衡。我们讨论了当前研究的局限性,并建议进一步的工作应该探索噬菌体是否可以普遍用于CF患者的肺部或其他无色杆菌感染。
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
Yale Journal of Biology and Medicine
Yale Journal of Biology and Medicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.00
自引率
0.00%
发文量
41
期刊介绍: The Yale Journal of Biology and Medicine (YJBM) is a graduate and medical student-run, peer-reviewed, open-access journal dedicated to the publication of original research articles, scientific reviews, articles on medical history, personal perspectives on medicine, policy analyses, case reports, and symposia related to biomedical matters. YJBM is published quarterly and aims to publish articles of interest to both physicians and scientists. YJBM is and has been an internationally distributed journal with a long history of landmark articles. Our contributors feature a notable list of philosophers, statesmen, scientists, and physicians, including Ernst Cassirer, Harvey Cushing, Rene Dubos, Edward Kennedy, Donald Seldin, and Jack Strominger. Our Editorial Board consists of students and faculty members from Yale School of Medicine and Yale University Graduate School of Arts & Sciences. All manuscripts submitted to YJBM are first evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field, and style. Suitable manuscripts are then subject to rigorous, fair, and rapid peer review.
×
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