The Flo Adhesin Family

Willaert, Ronnie; Kayacan, Yeseren; Devreese, Bart

doi:10.3390/pathogens10111397

Cited by 16 publications

(26 citation statements)

References 378 publications

(530 reference statements)

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“…Six of those were chosen along the ranked 71 homologs in gaps of 10 (starting from C. dubliniensis orthologs located five places away from the original C. albicans Als5). To these six, we added the emerging pathogen Candida auris, which was not a part of the homologs collected by the ConSurf webserver due to low sequence identity to the C. albicans Als5p (Willaert, 2018;Willaert et al, 2021). The multiple sequence alignment of the 71 homologs along with the C. auris sequence was obtained by reproducing the ConSurf search with similar parameters but lower sequence identity of 25%-95%, and then filtering out the irrelevant homologs using Jalview2.…”

Section: Calculation Of Evolutionary Conservation Using the Consurf/c...mentioning

confidence: 99%

Structure and Conservation of Amyloid Spines From the Candida albicans Als5 Adhesin

Golan

Schwartz-Perov

Landau

et al. 2022

Front. Mol. Biosci.

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Candida Als family adhesins mediate adhesion to biological and abiotic substrates, as well as fungal cell aggregation, fungal-bacterial co-aggregation and biofilm formation. The activity of at least two family members, Als5 and Als1, is dependent on amyloid-like protein aggregation that is initiated by shear force. Each Als adhesin has a ∼300-residue N-terminal Ig-like/invasin region. The following 108-residue, low complexity, threonine-rich (T) domain unfolds under shear force to expose a critical amyloid-forming segment 322SNGIVIVATTRTV334 at the interface between the Ig-like/invasin domain 2 and the T domain of Candida albicans Als5. Amyloid prediction programs identified six potential amyloidogenic sequences in the Ig-like/invasin region and three others in the T domain of C. albicans Als5. Peptides derived from four of these sequences formed fibrils that bound thioflavin T, the amyloid indicator dye, and three of these revealed atomic-resolution structures of cross-β spines. These are the first atomic-level structures for fungal adhesins. One of these segments, from the T domain, revealed kinked β-sheets, similarly to LARKS (Low-complexity, Amyloid-like, Reversible, Kinked segments) found in human functional amyloids. Based on the cross-β structures in Als proteins, we use evolutionary arguments to identify functional amyloidogenic sequences in other fungal adhesins, including adhesins from Candida auris. Thus, cross-β structures are often involved in fungal pathogenesis and potentially in antifungal therapy.

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Section: Calculation Of Evolutionary Conservation Using the Consurf/c...mentioning

confidence: 99%

Structure and Conservation of Amyloid Spines From the Candida albicans Als5 Adhesin

Golan

Schwartz-Perov

Landau

et al. 2022

Front. Mol. Biosci.

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“…Evaluation of biofilm formation and adherence in C. krusei led to the formation of floating biofilms and flocs, phenotypes that in S. cerevisiae are associated with the expression of flocculins in the cell wall (27). The flocculin (Flo) family of S. cerevisiae includes homologous Flo1, Flo5, Flo9 and Flo10 lectins that promote cell-cell adhesion by binding to mannose, which may lead to floc formation.…”

Section: Discussionmentioning

confidence: 99%

“…For the non-CTG clade pathogenic yeast Candida glabrata similar genomic studies demonstrated that it contains an extraordinarily large number of more than 70 sequences encoding GPI-modified adhesin-like proteins (21)(22)(23)(24)(25). Recent structural studies showed that most of these adhesins can be divided into two groups: (i) Epa1-related proteins with shown or presumed host-binding lectin activities and containing N-terminal PA14-like domains similar to flocculins in S. cerevisiae (26,27), and (ii) proteins with β-helix/βsandwich N-terminal domains for which the substrate ligands are still unidentified although involvement in adherence to polystyrene surfaces was demonstrated for Awp2 (28).…”

Section: Introductionmentioning

confidence: 99%

Integrated post-genomic cell wall analysis reveals floating biofilm formation associated with high expression of flocculins in the pathogenCandida krusei

Alvarado

Gómez-Navajas

Blázquez-Muñoz

et al. 2023

Preprint

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The pathogenic yeast Candida krusei is more distantly related to Candida albicans than clinically relevant CTG-clade Candida species. Its cell wall, a dynamic organelle that is the first point of interaction between pathogen and host, is relatively understudied, and its wall proteome remains unidentified to date. Here, we present an integrated study of the cell wall in C. krusei. Our comparative genomic studies and experimental data indicate that the general structure of the cell wall in C. krusei is similar to Saccharomyces cerevisiae and C. albicans and is comprised of β-1,3-glucan, β-1,6-glucan, chitin, and mannoproteins. However, some pronounced differences with C. albicans walls were observed, for instance, higher mannan and protein levels and altered protein mannosylation patterns. Further, despite absence of proteins with high sequence similarity to Candida adhesins, protein structure modeling identified eleven proteins related to flocculins/adhesins in S. cerevisiae or C. albicans. To obtain a proteomic comparison of biofilm and planktonic cells, C. krusei cells were grown to exponential phase and in static 24-h cultures. Interestingly, the 24-h static cultures of C. krusei yielded formation of floating biofilm (flor) rather than adherence to polystyrene at the bottom. The proteomic analysis of both conditions identified a total of 32 cell wall proteins. In line with a possible role in flor formation, increased abundance of flocculins, in particular Flo110, was observed in the floating biofilm compared to exponential cells. This study is the first to provide a detailed description of the cell wall in C. krusei including its cell wall proteome, and paves the way for further investigations on the importance of flor formation and flocculins in the pathogenesis of C. krusei.

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“…Six of those were chosen along the ranked 71 homologs in gaps of 10 (starting from C. dubliniensis orthologs located five places away from the original C. albicans Als5). To these six, we added the emerging pathogen Candida auris , which was not a part of the homologs collected by the ConSurf webserver due to low sequence identity to the C. albicans Als5p (54, 55). The multiple sequence alignment of the 71 homologs along with the C. auris sequence was obtained by re-producing the ConSurf search with similar parameters but lower sequence identity of 25-95%, and then filtering out the irrelevant homologs using Jalview2.…”

Section: Methodsmentioning

confidence: 99%

Structure and conservation of amyloid spines from the Candida albicans Als5 adhesin including similarity to human LARKS

Golan

Perov

Landau

et al. 2021

Preprint

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Candida Als family adhesins mediate adhesion to biological and abiotic substrates, as well as fungal cell aggregation and fungal-bacterial co-aggregation. The activity of at least two family members, Als5 and Als1, is dependent on amyloid-like protein aggregation that is initiated by shear force. Each Als adhesin has a ∼300-residue N-terminal Ig-like/invasin region. The following 108-residue, low complexity, threonine-rich (T) domain unfolds under shear to expose a critical amyloid-forming segment 322SNGIVIVATTRTV334 at the interface between the Ig-like/invasin domain 2 and the T domain of Candida albicans Als5. Amyloid prediction programs identified six potential amyloidogenic sequences in the Ig/invasin region and three others in the T domain of C. albicans Als5. Peptides derived from four of these sequences formed fibrils that bound thioflavin T, the amyloid indicator dye, and three of these revealed atomic-resolution structures of cross-β spines. These are the first atomic-level structures for fungal adhesins. One of these segments, from the T domain, revealed kinked β-sheets, similarly to LARKS (Low-complexity, Amyloid-like, Reversible, Kinked segments) found in human functional amyloids. Based on the cross-β structures in Als proteins, we use evolutionary arguments to identify functional amyloidogenic sequences in other fungal adhesins. Thus, cross-β structures are often involved in fungal pathogenesis and potentially in antifungal therapy.ImportanceFungal adhesins form cell-to-cell bonds in biofilms. Many of the cellular interactions are dependent on formation of amyloid-like cross-β protein aggregates. Such structures are called ‘functional amyloids’ because they perform physiological activities and they are dependent on the same types of protein interactions that form the more familiar amyloid deposits in neurodegenerative diseases. We have identified sequence segments that form cross-β structures in the Als5 adhesin from the human pathogen Candida albicans. Such sequences are widespread among ALS family adhesins, including those from other human pathogens including Candida auris. Moreover, we revealed a structural similarity in a segment originating from Als5 threonine-rich low complexity region to human LARKS, pointing on a common structural motif coding for functional amyloids in different kingdoms of life.

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The Flo Adhesin Family

Cited by 16 publications

References 378 publications

Structure and Conservation of Amyloid Spines From the Candida albicans Als5 Adhesin

Structure and Conservation of Amyloid Spines From the Candida albicans Als5 Adhesin

Integrated post-genomic cell wall analysis reveals floating biofilm formation associated with high expression of flocculins in the pathogenCandida krusei

Structure and conservation of amyloid spines from the Candida albicans Als5 adhesin including similarity to human LARKS

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