{"title":"Structural analysis of resistance-nodulation cell division transporters.","authors":"Philip A Klenotic, Edward W Yu","doi":"10.1128/mmbr.00198-23","DOIUrl":null,"url":null,"abstract":"<p><p>SUMMARYInfectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0000,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332337/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiology and Molecular Biology Reviews","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/mmbr.00198-23","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
SUMMARYInfectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.
期刊介绍:
Microbiology and Molecular Biology Reviews (MMBR), a journal that explores the significance and interrelationships of recent discoveries in various microbiology fields, publishes review articles that help both specialists and nonspecialists understand and apply the latest findings in their own research. MMBR covers a wide range of topics in microbiology, including microbial ecology, evolution, parasitology, biotechnology, and immunology. The journal caters to scientists with diverse interests in all areas of microbial science and encompasses viruses, bacteria, archaea, fungi, unicellular eukaryotes, and microbial parasites. MMBR primarily publishes authoritative and critical reviews that push the boundaries of knowledge, appealing to both specialists and generalists. The journal often includes descriptive figures and tables to enhance understanding. Indexed/Abstracted in various databases such as Agricola, BIOSIS Previews, CAB Abstracts, Cambridge Scientific Abstracts, Chemical Abstracts Service, Current Contents- Life Sciences, EMBASE, Food Science and Technology Abstracts, Illustrata, MEDLINE, Science Citation Index Expanded (Web of Science), Summon, and Scopus, among others.