{"title":"Phage-mediated colistin resistance in Acinetobacter baumannii","authors":"Massimiliano Lucidi , Francesco Imperi , Irene Artuso , Giulia Capecchi , Cinzia Spagnoli , Daniela Visaggio , Giordano Rampioni , Livia Leoni , Paolo Visca","doi":"10.1016/j.drup.2024.101061","DOIUrl":null,"url":null,"abstract":"<div><h3><em>Aims</em></h3><p>Antimicrobial resistance is a global threat to human health, and <em>Acinetobacter baumannii</em> is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant <em>A</em>. <em>baumannii</em> strains has forced the revival of colistin as a last-resort drug, suddenly leading to the emergence of colistin resistance. We investigated the genetic and molecular basis of colistin resistance in <em>A. baumannii</em>, and the mechanisms implicated in its regulation and dissemination.</p></div><div><h3><em>Methods</em></h3><p>Comparative genomic analysis was combined with genetic, biochemical, and phenotypic assays to characterize Φ19606, an <em>A</em>. <em>baumannii</em> temperate bacteriophage that carries a colistin resistance gene.</p></div><div><h3><em>Results</em></h3><p>Ф19606 was detected in 41% of 523 <em>A</em>. <em>baumannii</em> complete genomes and demonstrated to act as a mobile vehicle of the colistin resistance gene <em>eptA1</em>, encoding a functional lipid A phosphoethanolamine transferase<em>.</em> The <em>eptA1</em> gene is coregulated with its chromosomal homolog <em>pmrC</em> via the PmrAB two-component system and confers colistin resistance when induced by low calcium and magnesium levels. Resistance selection assays showed that the <em>eptA1</em>-harbouring phage Ф19606 promotes the emergence of spontaneous colistin-resistant mutants.</p></div><div><h3><em>Conclusions</em></h3><p>Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"73 ","pages":"Article 101061"},"PeriodicalIF":15.8000,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000190/pdfft?md5=e2e2dfa626e3a5985be906d1dbff90e9&pid=1-s2.0-S1368764624000190-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Resistance Updates","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1368764624000190","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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Abstract
Aims
Antimicrobial resistance is a global threat to human health, and Acinetobacter baumannii is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant A. baumannii strains has forced the revival of colistin as a last-resort drug, suddenly leading to the emergence of colistin resistance. We investigated the genetic and molecular basis of colistin resistance in A. baumannii, and the mechanisms implicated in its regulation and dissemination.
Methods
Comparative genomic analysis was combined with genetic, biochemical, and phenotypic assays to characterize Φ19606, an A. baumannii temperate bacteriophage that carries a colistin resistance gene.
Results
Ф19606 was detected in 41% of 523 A. baumannii complete genomes and demonstrated to act as a mobile vehicle of the colistin resistance gene eptA1, encoding a functional lipid A phosphoethanolamine transferase. The eptA1 gene is coregulated with its chromosomal homolog pmrC via the PmrAB two-component system and confers colistin resistance when induced by low calcium and magnesium levels. Resistance selection assays showed that the eptA1-harbouring phage Ф19606 promotes the emergence of spontaneous colistin-resistant mutants.
Conclusions
Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance.
期刊介绍：
Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation.
Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective.
*Expert reviews in clinical and basic drug resistance research in oncology and infectious disease
*Describes emerging technologies and therapies, particularly those that overcome drug resistance
*Emphasises common themes in microbial and cancer research
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