Candidiasis

Comparison between Candida albicans Agglutinin-Like Sequence Gene Expression Patterns in Human Clinical Specimens and Models of Vaginal Candidiasis

Georgina Cheng,1 Karen Wozniak,2 Matthew A. Wallig,1 Paul L. Fidel Jr.,2 Suzanne R. Trupin,3 and Lois L. Hoyer1*
Department of Veterinary Pathobiology,1 Department of Obstetrics and Gynecology, University of Illinois, Urbana, Illinois,3 Departmentof Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana2
Received 26 August 2004/ Returned for modification 13 September 2004/ Accepted 22 October 2004


|[pic]|   ABSTRACT |
|[pic]Top ||[pic]Abstract |
|[pic]Introduction |
|[pic]Materials and Methods |
|[pic]Results |
|[pic]Discussion |
|[pic]References |


 
Expression of the eight genes in the Candida albicans agglutinin-like sequence (ALS) family was studied by reverse transcription-PCR of RNA isolated from clinicalvaginal fluid specimens and vaginal candidiasis model systems. Although expression of all ALS genes was detected across the set of clinical specimens, ALS1, ALS2, ALS3, and ALS9 transcripts were detected most frequently, and expression of ALS4 and ALS5 was detected least frequently. Laboratory strain 3153A and two C. albicans strains isolated from the clinical specimens were studied using two modelsof vaginal candidiasis to determine how closely these models mimicked the clinical specimens at the level of gene expression. ALS gene expression patterns in a murine vaginitis model were identical to those from the clinical specimens. Expression of more ALS genes was detected in specimens collected 7 days after infection compared to those collected at 4 days. Similar patterns of ALS geneexpression were observed when the three C. albicans strains were tested in the reconstituted human vaginal epithelium model. In this model, expression of ALS4, ALS5, ALS6, and ALS7 was least frequently detected. Negative or weakened signals for ALS4 expression were observed at early time points, suggesting that ALS4 expression, which was strong in the inoculum cells, was down-regulated upon contact of C.albicans with vaginal epithelial cells in this model. The data presented here support the conclusion of host-site-specific influences on ALS gene expression and validate the use of the experimental models for evaluating the phenotype of als/als mutant strains.


|[pic]|   INTRODUCTION ||[pic]Top |
|[pic]Abstract |
|[pic]Introduction |
|[pic]Materials and Methods |
|[pic]Results |
|[pic]Discussion |
|[pic]References |


 
Approximately three-fourths of women experience an episode of vaginal candidiasis (29); Candida albicans is the etiologicalagent in over 80% of the cases (5, 29). C. albicans has many capabilities that aid its ability to cause disease, including phenotypic switching (30), filamentation (17), adherence (33), and secreted hydrolases (18). Some of these pathogenesis-associated factors are encoded by gene families including the agglutinin-like sequence (ALS) (10), secreted aspartyl proteinase (SAP) (20), and lipase (16)families. The eight ALS genes (ALS1 to ALS7 and ALS9) encode large, cell surface glycoproteins, some of which promote adhesion to host surfaces (6, 7, 10, 35, 36). Although they share a similar three-domain structure, sequence differences between the Als proteins can be large, suggesting that the proteins may have different functions (10). Differential expression of the ALS genes was demonstrated...