Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family--a sticky pursuit

Abstract

The agglutinin-like sequence (ALS) family of Candida albicans includes eight genes that encode large cell-surface glycoproteins. The high degree of sequence relatedness between the ALS genes and the tremendous allelic variability often present in the same C. albicans strain complicated definition and characterization of the gene family. The main hypothesis driving ALS family research is that the genes encode adhesins, primarily involved in host-pathogen interactions. Although adhesive function has been demonstrated for several Als proteins, the challenge of studying putative adhesins in a highly adhesive organism like C. albicans has led to varying ideas about how best to pursue such investigations, and results that are sometimes contradictory. Recent analysis of alsdelta/alsdelta strains suggested roles for Als proteins outside of adhesion to host surfaces, and a broader scope of Als protein function than commonly believed. The availability and use of experimental methodologies to study C. albicans at the genomic level, and the ALS family en masse, have advanced knowledge of these genes and emphasized their importance in C. albicans biology and pathogenesis.

Fig. 1

(A). Line drawing showing selected features of the C. albicans ALS genes. Color coding is used to show regions of similarity between genes and matches the color coding used in Fig. 1B. The length of the 5′ domain is similar in all ALS genes (approximately 1.3 kb) [1]. An “N” denotes the location of sequences encoding consensus N-glycosylation sites. The tandem repeat domain is drawn as individual repeated units to emphasize the composition of this portion of the coding region. The number of tandemly repeated copies in each ALS gene varies by C. albicans strain, and often between alleles within the same strain. For all genes except ALS9, the tandem repeat copy number depicted here represents the most common allele or mean of tandem repeat copy number observed from analysis of C. albicans strain collections (see text). For ALS9, the two alleles from strain SC5314 are shown [9, 10]. The variable length of the 3′ domain for each ALS gene is drawn to scale. There is a repeated domain in the 3′ end of ALS7 that is of variable length. The location of the repeated region is marked with parallel, diagonal lines. (B). An anthropomorphic presentation of ALS gene relationships: the updated C. albicans ALS family portrait. A similar image was published earlier [2] with detailed explanations of the meaning of various elements in the drawing. Briefly, heads of the human figures represent the 5′ domain of an ALS gene, torsos represent the central tandem repeat domain, and legs depict the 3′ domain. Portions of each human figure (hair, T-shirts, trouser legs and shoes) are color coded to indicate regions of high sequence identity/similarity between the various ALS genes. Differences between this image and the one published previously result from data that are summarized in the text of this manuscript. ALS8 was removed from the figure since that coding region is identical to ALS3 and encoded by a single locus [8]. ALS3 is wearing royal robes to indicate that deletion of this gene makes results in the largest decrease in C. albicans adhesion in the assays published to date [8]. This new diagram also depicts the allelic diversity found in ALS9 in strain SC5314 [9] including 5′ domain sequences that differ by 11% (represented by the two nearly identical heads) and the Variable Block regions of sequence present in the ALS9 3′ domain (shown as blocks on the trouser legs). The halo around one of the ALS9 heads indicates that a contribution to endothelial cell adhesion was measurable for the ALS9-2 5′ domain, but not for the corresponding region of ALS9-1 [10]. The new building under construction in the background of the image represents non-adhesive functions that have been detected for the Als proteins [12]. (Artwork by Kerry Helms, The Design Group @ Vet Med, University of Illinois, Urbana).

Fig. 1

(A). Line drawing showing selected features of the C. albicans ALS genes. Color coding is used to show regions of similarity between genes and matches the color coding used in Fig. 1B. The length of the 5′ domain is similar in all ALS genes (approximately 1.3 kb) [1]. An “N” denotes the location of sequences encoding consensus N-glycosylation sites. The tandem repeat domain is drawn as individual repeated units to emphasize the composition of this portion of the coding region. The number of tandemly repeated copies in each ALS gene varies by C. albicans strain, and often between alleles within the same strain. For all genes except ALS9, the tandem repeat copy number depicted here represents the most common allele or mean of tandem repeat copy number observed from analysis of C. albicans strain collections (see text). For ALS9, the two alleles from strain SC5314 are shown [9, 10]. The variable length of the 3′ domain for each ALS gene is drawn to scale. There is a repeated domain in the 3′ end of ALS7 that is of variable length. The location of the repeated region is marked with parallel, diagonal lines. (B). An anthropomorphic presentation of ALS gene relationships: the updated C. albicans ALS family portrait. A similar image was published earlier [2] with detailed explanations of the meaning of various elements in the drawing. Briefly, heads of the human figures represent the 5′ domain of an ALS gene, torsos represent the central tandem repeat domain, and legs depict the 3′ domain. Portions of each human figure (hair, T-shirts, trouser legs and shoes) are color coded to indicate regions of high sequence identity/similarity between the various ALS genes. Differences between this image and the one published previously result from data that are summarized in the text of this manuscript. ALS8 was removed from the figure since that coding region is identical to ALS3 and encoded by a single locus [8]. ALS3 is wearing royal robes to indicate that deletion of this gene makes results in the largest decrease in C. albicans adhesion in the assays published to date [8]. This new diagram also depicts the allelic diversity found in ALS9 in strain SC5314 [9] including 5′ domain sequences that differ by 11% (represented by the two nearly identical heads) and the Variable Block regions of sequence present in the ALS9 3′ domain (shown as blocks on the trouser legs). The halo around one of the ALS9 heads indicates that a contribution to endothelial cell adhesion was measurable for the ALS9-2 5′ domain, but not for the corresponding region of ALS9-1 [10]. The new building under construction in the background of the image represents non-adhesive functions that have been detected for the Als proteins [12]. (Artwork by Kerry Helms, The Design Group @ Vet Med, University of Illinois, Urbana).