Functional Amyloids Keep Quorum-sensing Molecules in Check

Seviour, Thomas; Hansen, Susan Hove; Yang, Liang; Yau, Yin Hoe; Wang, Victor Bochuan; Stenvang, Marcel; Christiansen, Gunna; Marsili, Enrico; Givskov, Michael; Chen, Yicai; Otzen, Daniel E.; Nielsen, Per Halkjær; Geifman-Shochat, Susana; Kjelleberg, Staffan; Dueholm, Morten Simonsen

doi:10.1074/jbc.m114.613810

Cited by 79 publications

(73 citation statements)

References 74 publications

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“…Figure S4 shows the structural evolution of the LG21 peptide when it interacts with the Psl. It is observed that the middle residues (6)(7)(8)(9)(10)(11)(12)(13)(14) are the main contributors to the helical conformation. The reason could be that the presence of carbohydrate chain (Psl) in the solution decreases the polar nature of water to form hydrogen bonds with the middle residues and the increasing hydrophobic interactions within the peptide induces the helical structure, whereas the terminal residues still have a random-coil structure by being exposed to the aqueous solution.…”

Section: Molecular Dynamics (Md) Simulation Of Psl-lg21 Binding Modementioning

confidence: 99%

Pseudomonas aeruginosa Psl Exopolysaccharide Interacts with the Antimicrobial Peptide LG21

Chin

Sinha

Nalaparaju

et al. 2017

Water

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Biofilm formation by opportunistic pathogens serves as one of the major causes of chronic and persistent infections. Bacterial cells in the biofilms are embedded in their self-generated protective extracellular polymeric substances (EPS), which include exopolysaccharides, large adhesin proteins and extracellular DNA. In this study, we identified an antimicrobial peptide (AMP) LG21 that is able to interact specifically with the Psl exopolysaccharide of Pseudomonas aeruginosa, thus it can be used as a diagnostic tool for P. aeruginosa biofilms. Molecular dynamics simulation analysis showed that residues numbered from 15 to 21 (WKRKRFG) in LG21 are involved in interacting with Psl. Our study indicates that host immune systems might detect and interact with microbial biofilms through AMPs. Engineering biofilm EPS-targeting AMPs might provide novel strategies for biofilm detection and treatment.

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Section: Molecular Dynamics (Md) Simulation Of Psl-lg21 Binding Modementioning

confidence: 99%

Pseudomonas aeruginosa Psl Exopolysaccharide Interacts with the Antimicrobial Peptide LG21

Chin

Sinha

Nalaparaju

et al. 2017

Water

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“…Biofilm-associated bacteria, in particular, utilize amyloids as a building material to reinforce the EM and resist dispersion by chemical or mechanical agents [8, 11]. These fibrils may also promote antibiotic resistance and act as a reservoir for small molecules involved in quorum sensing [12, 13]. Amyloid fibrils polymerize in the absence of an energy source, so they serve as a metabolically advantageous molecular scaffold despite the limited resources of the EM environment [14].…”

Section: Introductionmentioning

confidence: 99%

Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms

Bleem

Christiansen

Madsen

et al. 2018

Journal of Molecular Biology

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Amyloids are typically associated with neurodegenerative diseases, but recent research demonstrates that several bacteria utilize functional amyloid fibrils to fortify the biofilm extracellular matrix and thereby resist antibiotic treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly of FapC, a protein with high-sequence conservation among the genera. Previous studies established FapC as the major amyloid subunit, but its mechanism of fibril formation in P. aeruginosa remained largely unexplored. Here, we examine the FapC sequence in greater detail through a combination of bioinformatics and protein engineering, and we identify specific motifs that are implicated in amyloid formation. Sequence regions of high evolutionary conservation tend to coincide with regions of high amyloid propensity, and mutation of amyloidogenic motifs to a designed, non-amyloidogenic motif suppresses fibril formation in a pH-dependent manner. We establish the particular significance of the third repeat motif in promoting fibril formation and also demonstrate emergence of soluble oligomer species early in the aggregation pathway. The insights reported here expand our understanding of the mechanism of amyloid polymerization in P. aeruginosa, laying the foundation for development of new amyloid inhibitors to combat recalcitrant biofilm infections.

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“…Fap fibrils have been shown to bind extracellular metabolites within the biofilm, such as quorum-sensing molecules and redox mediators, modulating their release and retention when required. This implies a potential new role for functional amyloids in molecular retention and indirect mediation of cell function (7,39,40) Again, genes encoding proteins with homology to the Fap systems are present within species belonging to the Beta-, Gamma-, and Deltaproteobacteria (38).…”

Section: Amyloid Structures With Dedicated Fiber Assembly Machinerymentioning

confidence: 99%

Amyloid Structures as Biofilm Matrix Scaffolds

2016

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bRecent insights into bacterial biofilm matrix structures have induced a paradigm shift toward the recognition of amyloid fibers as common building block structures that confer stability to the exopolysaccharide matrix. Here we describe the functional amyloid systems related to biofilm matrix formation in both Gram-negative and Gram-positive bacteria and recent knowledge regarding the interaction of amyloids with other biofilm matrix components such as extracellular DNA (eDNA) and the host immune system. In addition, we summarize the efforts to identify compounds that target amyloid fibers for therapeutic purposes and recent developments that take advantage of the amyloid structure to engineer amyloid fibers of bacterial biofilm matrices for biotechnological applications.

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Functional Amyloids Keep Quorum-sensing Molecules in Check

Cited by 79 publications

References 74 publications

Pseudomonas aeruginosa Psl Exopolysaccharide Interacts with the Antimicrobial Peptide LG21

Pseudomonas aeruginosa Psl Exopolysaccharide Interacts with the Antimicrobial Peptide LG21

Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms

Amyloid Structures as Biofilm Matrix Scaffolds

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