Role of Bcr1-Activated Genes Hwp1 and Hyr1 in Candida Albicans Oral Mucosal Biofilms and Neutrophil Evasion

Department of Microbiology, University of Texas, Houston, Texas, United States of America.
PLoS ONE (Impact Factor: 3.23). 01/2011; 6(1):e16218. DOI: 10.1371/journal.pone.0016218
Source: PubMed


Candida albicans triggers recurrent infections of the oropharyngeal mucosa that result from biofilm growth. Prior studies have indicated that the transcription factor Bcr1 regulates biofilm formation in a catheter model, both in vitro and in vivo. We thus hypothesized that Bcr1 plays similar roles in the formation of oral mucosal biofilms and tested this hypothesis in a mouse model of oral infection. We found that a bcr1/bcr1 mutant did not form significant biofilm on the tongues of immunocompromised mice, in contrast to reference and reconstituted strains that formed pseudomembranes covering most of the tongue dorsal surface. Overexpression of HWP1, which specifies an epithelial adhesin that is under the transcriptional control of Bcr1, partly but significantly rescued the bcr1/bcr1 biofilm phenotype in vivo. Since HWP1 overexpression only partly reversed the biofilm phenotype, we investigated whether additional mechanisms, besides adhesin down-regulation, were responsible for the reduced virulence of this mutant. We discovered that the bcr1/bcr1 mutant was more susceptible to damage by human leukocytes when grown on plastic or on the surface of a human oral mucosa tissue analogue. Overexpression of HYR1, but not HWP1, significantly rescued this phenotype. Furthermore a hyr1/hyr1 mutant had significantly attenuated virulence in the mouse oral biofilm model of infection. These discoveries show that Bcr1 is critical for mucosal biofilm infection via regulation of epithelial cell adhesin and neutrophil function.


Available from: ZHIHONG XIE, Apr 29, 2014
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    • "An important regulator of C. albicans biofilm formation is the transcription factor Bcr1, which is a positive regulator of several candidal adhesin genes including HYR1, HWP1, CHT2, ECE1, RBT5, ALS1, and ALS3 (43, 44). The importance of Bcr1 in C. albicans biofilm formation within in a mouse model of oral infection has recently been demonstrated (45). "
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    ABSTRACT: Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. The organism is however, commonly encountered as a commensal in healthy individuals where it is a component of the normal microflora. The key determinant in the type of relationship that Candida has with its host is how it interacts with the epithelial surface it colonises. A delicate balance clearly exists between the potentially damaging effects of Candida virulence factors and the nature of the immune response elicited by the host. Frequently, it is changes in host factors that lead to Candida seemingly changing from a commensal to pathogenic existence. However, given the often reported heterogeneity in morphological and biochemical factors that exist between Candida species and indeed strains of C. albicans, it may also be the fact that colonising strains differ in the way they exploit resources to allow persistence at mucosal surfaces and as a consequence this too may affect the way Candida interacts with epithelial cells. The aim of this review is to provide an overview of some of the possible interactions that may occur between C. albicans and host epithelial surfaces that may in turn dictate whether Candida removal, its commensal persistence or infection follows.
    Journal of Oral Microbiology 10/2013; 5. DOI:10.3402/jom.v5i0.22434
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    • "In C. albicans, the agglutinin-like sequence (ALS) genes have been revealed to have close relationship with biofilms formation [35], [36]. It was proved that overexpression of ALS3 leads to an increase in biofilms mass [37], while overexpression of HWP1, the necessary factor for normal biofilms formation in vitro and in vivo could effectively restores the ability of a bcr1D null strain to form biofilms on murine mucosal surfaces [38]–[40]. In this study, we found all the genes were downregulated after RCD treatment compared with the control, indicating RCD affects C. albicans biofilms formation by inhibiting Ras-cAMP-Efg signalling pathway. "
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    PLoS ONE 04/2012; 7(4):e35543. DOI:10.1371/journal.pone.0035543 · 3.23 Impact Factor
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    • "In particular, genes missing from the C. dubliniensis genome include those encoding hypha-specific virulence factors, such as the cell surface proteins Hyr1 and Als3 and two members of the secreted aspartyl proteinase family (i.e., Sap5 and Sap6), while the gene encoding the well-characterized epithelial adhesin Hwp1 is highly divergent [31, 32]. Hyr1 has been shown to confer resistance to neutrophil killing activity [34] and, along with Hwp1, has been shown recently to play an important role in oral mucosal biofilm formation [35]. Als3 has been shown to play an important role in adhesion to host cells and has been shown to have invasin-like [36] and iron-sequestering [37] activity, while the Saps are well-known virulence factors [21]. "
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