{"title":"Therapeutic Approaches Targeting the Assembly and Function of Chaperone-Usher Pili.","authors":"John J Psonis, David G Thanassi","doi":"10.1128/ecosalplus.ESP-0033-2018","DOIUrl":null,"url":null,"abstract":"<p><p>The chaperone-usher (CU) pathway is a conserved secretion system dedicated to the assembly of a superfamily of virulence-associated surface structures by a wide range of Gram-negative bacteria. Pilus biogenesis by the CU pathway requires two specialized assembly components: a dedicated periplasmic chaperone and an integral outer membrane assembly and secretion platform termed the usher. The CU pathway assembles a variety of surface fibers, ranging from thin, flexible filaments to rigid, rod-like organelles. Pili typically act as adhesins and function as virulence factors that mediate contact with host cells and colonization of host tissues. Pilus-mediated adhesion is critical for early stages of infection, allowing bacteria to establish a foothold within the host. Pili are also involved in modulation of host cell signaling pathways, bacterial invasion into host cells, and biofilm formation. Pili are critical for initiating and sustaining infection and thus represent attractive targets for the development of antivirulence therapeutics. Such therapeutics offer a promising alternative to broad-spectrum antibiotics and provide a means to combat antibiotic resistance and treat infection while preserving the beneficial microbiota. A number of strategies have been taken to develop antipilus therapeutics, including vaccines against pilus proteins, competitive inhibitors of pilus-mediated adhesion, and small molecules that disrupt pilus biogenesis. Here we provide an overview of the function and assembly of CU pili and describe current efforts aimed at interfering with these critical virulence structures.</p>","PeriodicalId":11500,"journal":{"name":"EcoSal Plus","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422168/pdf/nihms-1006342.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EcoSal Plus","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1128/ecosalplus.ESP-0033-2018","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
The chaperone-usher (CU) pathway is a conserved secretion system dedicated to the assembly of a superfamily of virulence-associated surface structures by a wide range of Gram-negative bacteria. Pilus biogenesis by the CU pathway requires two specialized assembly components: a dedicated periplasmic chaperone and an integral outer membrane assembly and secretion platform termed the usher. The CU pathway assembles a variety of surface fibers, ranging from thin, flexible filaments to rigid, rod-like organelles. Pili typically act as adhesins and function as virulence factors that mediate contact with host cells and colonization of host tissues. Pilus-mediated adhesion is critical for early stages of infection, allowing bacteria to establish a foothold within the host. Pili are also involved in modulation of host cell signaling pathways, bacterial invasion into host cells, and biofilm formation. Pili are critical for initiating and sustaining infection and thus represent attractive targets for the development of antivirulence therapeutics. Such therapeutics offer a promising alternative to broad-spectrum antibiotics and provide a means to combat antibiotic resistance and treat infection while preserving the beneficial microbiota. A number of strategies have been taken to develop antipilus therapeutics, including vaccines against pilus proteins, competitive inhibitors of pilus-mediated adhesion, and small molecules that disrupt pilus biogenesis. Here we provide an overview of the function and assembly of CU pili and describe current efforts aimed at interfering with these critical virulence structures.
EcoSal PlusImmunology and Microbiology-Microbiology
CiteScore
12.20
自引率
0.00%
发文量
4
期刊介绍:
EcoSal Plus is the authoritative online review journal that publishes an ever-growing body of expert reviews covering virtually all aspects of E. coli, Salmonella, and other members of the family Enterobacteriaceae and their use as model microbes for biological explorations. This journal is intended primarily for the research community as a comprehensive and continuously updated archive of the entire corpus of knowledge about the enteric bacterial cell. Thoughtful reviews focus on physiology, metabolism, genetics, pathogenesis, ecology, genomics, systems biology, and history E. coli and its relatives. These provide the integrated background needed for most microbiology investigations and are essential reading for research scientists. Articles contain links to E. coli K12 genes on the EcoCyc database site and are available as downloadable PDF files. Images and tables are downloadable to PowerPoint files.