Using Genomics to Shape the Definition of the Agglutinin-Like Sequence (ALS) Family in the Saccharomycetales.

Soon-Hwan Oh,Allyson Isenhower,Alvaro G Hernandez,Lois L Hoyer,Rubi Rodriguez-Bobadilla,Vien M Vuong,Christopher J Fields,Klaus Schliep

doi:10.3389/fcimb.2021.794529

Abstract

The Candida albicans agglutinin-like sequence (ALS) family is studied because of its contribution to cell adhesion, fungal colonization, and polymicrobial biofilm formation. The goal of this work was to derive an accurate census and sequence for ALS genes in pathogenic yeasts and other closely related species, while probing the boundaries of the ALS family within the Order Saccharomycetales. Bioinformatic methods were combined with laboratory experimentation to characterize 47 novel ALS loci from 8 fungal species. AlphaFold predictions suggested the presence of a conserved N-terminal adhesive domain (NT-Als) structure in all Als proteins reported to date, as well as in S. cerevisiae alpha-agglutinin (Sag1). Lodderomyces elongisporus, Meyerozyma guilliermondii, and Scheffersomyces stipitis were notable because each species had genes with C. albicans ALS features, as well as at least one that encoded a Sag1-like protein. Detection of recombination events between the ALS family and gene families encoding other cell-surface proteins such as Iff/Hyr and Flo suggest widespread domain swapping with the potential to create cell-surface diversity among yeast species. Results from the analysis also revealed subtelomeric ALS genes, ALS pseudogenes, and the potential for yeast species to secrete their own soluble adhesion inhibitors. Information presented here supports the inclusion of SAG1 in the ALS family and yields many experimental hypotheses to pursue to further reveal the nature of the ALS family.

Highlights

Most knowledge about agglutinin-like sequence (Als) protein structure and function comes from the study of Candida albicans
The availability of the unprecedented protein structural prediction accuracy of AlphaFold (Jumper et al, 2021) provided the opportunity to demonstrate conservation of N-terminal adhesive domain (NT-Als) domain shape for the proteins listed in Supplementary Table S2
The information leads to the conclusions that S. cerevisiae Sag1 is an Als protein and the Als family is far more diverse than previously described

Summary

Introduction

Most knowledge about agglutinin-like sequence (Als) protein structure and function comes from the study of Candida albicans (reviewed in Hoyer and Cota, 2016). C. albicans Als proteins are adhesins that promote interactions between fungi and host cells, establishing colonization that provides the opportunity to cause disease. Als proteins function in C. albicans adhesion to ALS Genes in the Saccharomycetales abiotic surfaces such as indwelling medical devices, and between fungi and other microbes such as bacteria, seeding polymicrobial biofilm development (Peters et al, 2012). Display of the NT-Als adhesive domain on the cell surface is key for its ability to interact with other cells and materials (Lin et al, 2014)

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