What We Do Not Know about Fungal Cell Adhesion Molecules

Abstract

There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from the six other fungal phyla are only sparsely described in the literature. In these other phyla, most of the research is at the cellular level, rather than at the molecular level, so there has been little characterization of the adhesion molecules themselves. A catalog of known adhesins shows some common features: high Ser/Thr content, tandem repeats, N- and O-glycosylations, GPI anchors, dibasic sequence motifs, and potential amyloid-forming sequences. However, none of these features is universal. Known ligands include proteins and glycans on homologous cells and host cells. Existing and novel tools can exploit the availability of genome sequences to identify and characterize new fungal adhesins. These include bioinformatics tools and well-established yeast surface display models, which could be coupled with an adhesion substrate array. Thus, new knowledge could be exploited to answer key questions in fungal ecology, animal and plant pathogenesis, and roles of biofilms in infection and biomass turnover.

De novo genome assembly of Candida glabrata reveals cell wall protein complement and structure of dispersed tandem repeat arrays

“…Several groups have previously undertaken substantial analysis of sequence motifs within the GPI‐CWP genes of C. glabrata , and with the correct sequence in hand, we present here a re‐analysis of motifs, hydrophobicity and the potential of beta‐aggregation for GPI‐CWP ALPs. All the GPI‐anchored ALPs encode Serine‐/Threonine‐rich region(s), as previously noted (Lipke, ). Thierry et al () documented large tandem repeat (length of repeat unit ≥135 nt) which they term megasatellites, and classified these based on their containing SHITT, SFFIT or TTITL 5 amino acid motifs.…”

“…In our assembly, 17 GPI‐anchored ALPs contain the SHITT motif; 38 GPI‐anchored ALPs contain the SFFIT motif; 6 GPI‐anchored ALPs encode the TTITL motif (Table ). Previous work has demonstrated the potential of GPI‐CWPs to aggregate forming amyloid‐like structures (Lipke, ) and implicates interaction between GPI‐CWPs in global cell wall organization (Alsteens, Garcia, Lipke, & Dufrêne, ). In identifying motifs that might be responsible for mediating protein‐protein aggregation, Lipke et al.…”

Expression of genes containing tandem repeat patterns involved in the fungal‐host interaction and in the response to antifungals inTrichophyton rubrum

“…It is known that the larger the number of TRs in the genome, the greater the capacity of cell‐cell junction and surface adhesion, especially when these repeats are present in regions encoding cell surface proteins. This fact has been well documented in the literature, 11,16,17 particularly for yeast 14 . In Saccharomyces cerevisiae , size variation of a gene creates quantitative phenotypic alterations (eg adhesion, flocculation, biofilm formation), that is the variation in intragenic repeat number provides the functional diversity of cell surface antigens that, in fungi and other pathogens, favours rapid adaptation to the environment and/or evasion of the host immune system 16 .…”

“…AMB is a broad‐spectrum antifungal drug that has been used parenterally for many years. It remains the ‘gold standard’ for the treatment of disseminated invasive microorganisms 11 . It binds to ergosterol and induces formation of pores that cause rapid leakage of monovalent ions (K + , Na + , H + and Cl − ) and subsequent fungal cell death.…”

“…There is evidence indicating that host cell signalling is manipulated during the early stages of infection in many species, ensuring evasion of the host immune responses and thus guaranteeing effective adhesion and dissemination of infection 10 . Little is known about the factors that mediate the adhesion of dermatophytes 11 . However, the capacity of T rubrum to adhere to epithelial cells has been attributed to proteins such as adhesins present on the surface of the conidial cell wall 12 …”