气候变化领域集成服务门户(CCPortal): Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition

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DOI	10.1073/pnas.2109940118
	Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition
	Melia C.E.; Bolla J.R.; Katharios-Lanwermeyer S.; Mihaylov D.B.; Hoffmann P.C.; Huo J.; Wozny M.R.; Elfari L.M.; Böhning J.; Morgan A.N.; Hitchman C.J.; Owens R.J.; Robinson C.V.; O'Toole G.A.; Bharat T.A.M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:31
英文摘要	Many bacteria, including the major human pathogen Pseudomonas aeruginosa, are naturally found in multicellular, antibiotic-tolerant biofilm communities, in which cells are embedded in an extracellular matrix of polymeric molecules. Cell-cell interactions within P. aeruginosa biofilms are mediated by CdrA, a large, membrane-associated adhesin present in the extracellular matrix of biofilms, regulated by the cytoplasmic concentration of cyclic diguanylate. Here, using electron cryotomography of focused ion beam-milled specimens, we report the architecture of CdrA molecules in the extracellular matrix of P. aeruginosa biofilms at intact cell-cell junctions. Combining our in situ observations at cell-cell junctions with biochemistry, native mass spectrometry, and cellular imaging, we demonstrate that CdrA forms an extended structure that projects from the outer membrane to tether cells together via polysaccharide binding partners. We go on to show the functional importance of CdrA using custom single-domain antibody (nanobody) binders. Nanobodies targeting the tip of functional cell-surface CdrA molecules could be used to inhibit bacterial biofilm formation or disrupt preexisting biofilms in conjunction with bactericidal antibiotics. These results reveal a functional mechanism for cell-cell interactions within bacterial biofilms and highlight the promise of using inhibitors targeting biofilm cell-cell junctions to prevent or treat problematic, chronic bacterial infections. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antibiotics; Biofilms; Cryo-EM; In situ imaging; Nanobody
语种	英语
scopus关键词	adhesin; CdrA protein, Pseudomonas aeruginosa; nanobody; bacterium adherence; biofilm; cell membrane; extracellular matrix; gene expression regulation; genetics; growth, development and aging; metabolism; physiology; Pseudomonas aeruginosa; Adhesins, Bacterial; Bacterial Adhesion; Biofilms; Cell Membrane; Extracellular Matrix; Gene Expression Regulation, Bacterial; Pseudomonas aeruginosa; Single-Domain Antibodies
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251090
作者单位	Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom; Central Oxford Structural Microscopy and Imaging Centre, University of Oxford, Oxford, OX1 3RE, United Kingdom; Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3TA, United Kingdom; Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, United States; Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom; Protein Production Facility United Kingdom, Rosalind Franklin Institute, Research Complex at Harwell, Didcot, OX11 0FA, United Kingdom; Division of Structural Biology, The Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom
推荐引用方式 GB/T 7714	Melia C.E.,Bolla J.R.,Katharios-Lanwermeyer S.,et al. Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition[J],2021,118(31).
APA	Melia C.E..,Bolla J.R..,Katharios-Lanwermeyer S..,Mihaylov D.B..,Hoffmann P.C..,...&Bharat T.A.M..(2021).Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA	Melia C.E.,et al."Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).