The biofilm-associated surface protein Esp of Enterococcus faecalis forms amyloid-like fibers

Taglialegna, Agustina; Matilla-Cuenca, Leticia; Dorado-Morales, Pedro; Navarro, Susanna; Ventura, Salvador; Garnett, James A.; Lasa, Íñigo; Valle, Jaione

doi:10.1038/s41522-020-0125-2

Cited by 51 publications

(75 citation statements)

References 42 publications

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“…Homologous Bap proteins are present in many pathogenic bacteria. Our previous results suggest that the mechanism of amyloid-like aggregation might be widespread among these proteins 17 , 20 . This assumption opens an exciting line of research to consider BAP proteins as molecular targets of polyphenols to fight against biofilm related infections.…”

Section: Discussionmentioning

confidence: 91%

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Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids

Matilla-Cuenca

Gil

Cuesta

et al. 2020

Sci Rep

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The opportunistic pathogen Staphylococcus aureus is responsible for causing infections related to indwelling medical devices, where this pathogen is able to attach and form biofilms. The intrinsic properties given by the self-produced extracellular biofilm matrix confer high resistance to antibiotics, triggering infections difficult to treat. Therefore, novel antibiofilm strategies targeting matrix components are urgently needed. The Biofilm Associated Protein, Bap, expressed by staphylococcal species adopts functional amyloid-like structures as scaffolds of the biofilm matrix. In this work we have focused on identifying agents targeting Bap-related amyloid-like aggregates as a strategy to combat S. aureus biofilm-related infections. We identified that the flavonoids, quercetin, myricetin and scutellarein specifically inhibited Bap-mediated biofilm formation of S. aureus and other staphylococcal species. By using in vitro aggregation assays and the cell-based methodology for generation of amyloid aggregates based on the Curli-Dependent Amyloid Generator system (C-DAG), we demonstrated that these polyphenols prevented the assembly of Bap-related amyloid-like structures. Finally, using an in vivo catheter infection model, we showed that quercetin and myricetin significantly reduced catheter colonization by S. aureus. These results support the use of polyphenols as anti-amyloids molecules that can be used to treat biofilm-related infections.

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Section: Discussionmentioning

confidence: 91%

“…Others Bap homologs behave the same way. The cleavage of N-terminal domain is enough for the formation of amyloid fibers 17 , 20 . However, in S. epidermidis, the C-repeat domain contains amyloid peptides that are sufficient for spontaneous formation of amyloid fibers 21 .…”

Section: Introductionmentioning

confidence: 99%

Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids

Matilla-Cuenca

Gil

Cuesta

et al. 2020

Sci Rep

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“…This approach was successfully tested using several known yeast amyloidogenic proteins (Sup35NM, Rnq1, Cyc8, and New1) and polyQ (aggregating) region of human huntingtin (Htt72Q), while the non-aggregating linker domain of yeast Sup35 protein (Sup35M) and non-aggregating derivative of human huntingtin (Htt25Q) were used as negative controls [ 242 ]. At subsequent stages, the C-DAG system was used to confirm the amyloidogenic properties of several yeast proteins (Mss11 and Pub1 [ 242 ], Gas1 and Ygp1 [ 238 ], and Toh1 [ 240 ]), some bacterial proteins (biofilm-associated proteins especially from Enterococcus faecalis and Bap from S. aureus [ 244 ], RopA and RopB from Rhizobium leguminosarum [ 237 ], and YghJ from E.coli [ 239 ]), and Fxr1 protein from rat Rattus norvegicus [ 120 ]. C-DAG approach was suggested as a convenient method for screening of potentially amyloidogenic proteins from DNA libraries [ 242 ].…”

Section: Approaches For Identification Of New Amyloids and Potentimentioning

confidence: 99%

“… The principle of C-DAG approach (for detail, see [ 244 ]). A chimeric protein, containing the export signal sequence of CsgA protein fused to the protein of interest is exposed to the extracellular space.…”

Section: Figurementioning

confidence: 99%

Functional Mammalian Amyloids and Amyloid-Like Proteins

Rubel

Fedotov

Grizel

et al. 2020

Life

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Amyloids are highly ordered fibrous cross-β protein aggregates that are notorious primarily because of association with a variety of incurable human and animal diseases (termed amyloidoses), including Alzheimer’s disease (AD), Parkinson’s disease (PD), type 2 diabetes (T2D), and prion diseases. Some amyloid-associated diseases, in particular T2D and AD, are widespread and affect hundreds of millions of people all over the world. However, recently it has become evident that many amyloids, termed “functional amyloids,” are involved in various activities that are beneficial to organisms. Functional amyloids were discovered in diverse taxa, ranging from bacteria to mammals. These amyloids are involved in vital biological functions such as long-term memory, storage of peptide hormones and scaffolding melanin polymerization in animals, substrate attachment, and biofilm formation in bacteria and fungi, etc. Thus, amyloids undoubtedly are playing important roles in biological and pathological processes. This review is focused on functional amyloids in mammals and summarizes approaches used for identifying new potentially amyloidogenic proteins and domains.

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“…S. aureus Δ bap strain cell titer is also significantly lower at 10 days post-infection [ 51 ]. Notably, Esp—the Bap ortholog of Enterococcus faecalis , a commensal bacterium capable of inducing nosocomial infection—forms amyloids, supporting the idea of the prevalence of amyloid formation by Bap-like proteins in biofilm matrix [ 53 ].…”

Section: Amyloids Of Biofilms and Their Involvement In Host–pathogmentioning

confidence: 92%

Biological Functions of Prokaryotic Amyloids in Interspecies Interactions: Facts and Assumptions

Kosolapova

Antonets

Белоусов

et al. 2020

IJMS

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Amyloids are fibrillar protein aggregates with an ordered spatial structure called “cross-β”. While some amyloids are associated with development of approximately 50 incurable diseases of humans and animals, the others perform various crucial physiological functions. The greatest diversity of amyloids functions is identified within prokaryotic species where they, being the components of the biofilm matrix, function as adhesins, regulate the activity of toxins and virulence factors, and compose extracellular protein layers. Amyloid state is widely used by different pathogenic bacterial species in their interactions with eukaryotic organisms. These amyloids, being functional for bacteria that produce them, are associated with various bacterial infections in humans and animals. Thus, the repertoire of the disease-associated amyloids includes not only dozens of pathological amyloids of mammalian origin but also numerous microbial amyloids. Although the ability of symbiotic microorganisms to produce amyloids has recently been demonstrated, functional roles of prokaryotic amyloids in host–symbiont interactions as well as in the interspecies interactions within the prokaryotic communities remain poorly studied. Here, we summarize the current findings in the field of prokaryotic amyloids, classify different interspecies interactions where these amyloids are involved, and hypothesize about their real occurrence in nature as well as their roles in pathogenesis and symbiosis.

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The biofilm-associated surface protein Esp of Enterococcus faecalis forms amyloid-like fibers

Cited by 51 publications

References 42 publications

Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids

Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids

Functional Mammalian Amyloids and Amyloid-Like Proteins

Biological Functions of Prokaryotic Amyloids in Interspecies Interactions: Facts and Assumptions

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