Biofilm matrix regulation by Candida glabrata Zap1 under acidic conditions: transcriptomic and proteomic analyses
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PROVIDER: PRJNA942261 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptional profiling of Candida glabrata zap1Δ and zap1Δ::ZAP1 strains, comparing cells grown under planktonic and biofilm-inducing conditions. Goal was to analyse the effect of ZAP1 deletion in the transcriptomic profile of C. glabrata biofilm cells (in comparision to planktonic cells), under acidic conditions, in order to study the function of the Zap1 transcription factor in C. glabrata biofilm matrix production.
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Project description:The vaginal acidic environment potentiates the formation of Candida glabrata biofilms, leading to complicated and recurrent infections. Importantly, the regulation of biofilm matrix is known to contribute to the recalcitrant features of Candida biofilms. In this study we reveal a new matrix regulator of C. glabrata acidic biofilms, Zap1, and analyzed its modulation of the transcriptome (by microarrays) and matrix proteome (by LC-MS/MS). For that, the deletion mutant zap1Δ and its complemented strain zap1Δ::ZAP1 were constructed and their biofilms were developed at pH 4 (adjusted with lactic acid). The results revealed that Zap1 is a negative regulator of the total amount of protein and carbohydrate in the biofilm matrix. Accordingly, various genes and matrix proteins with predicted functions in the regulation of carbohydrate metabolism, sugar binding, sugar transport and adhesion (including Epa family) were found to be repressed by Zap1. Nevertheless, the results also suggested that Zap1 is essential to the delivery and organization of some matrix components. Indeed, Zap1 was required to the secretion of 122 proteins to the matrix and induced the expression of 557 genes, including various targets involved in glucan-metabolism. Additionally, Zap1 induced targets with roles in virulence, resistance to antifungals and host immunity evasion, including yapsins, ERG family and moonlighting proteins. Zap1 was also required to the secretion of acidic-specific matrix proteins, indicating a contribution to the response to the acidic environment. Overall, this study demonstrates that Zap1 is a relevant regulator of biofilm matrix, contributing to a better understanding of C. glabrata acidic biofilms.
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Project description:Candida glabrata is a clinically relevant human pathogen with ability to form high recalcitrant biofilms that contribute to the establishment and persistence of infection. A defining trait of biofilms is the auto-produced matrix, which is suggested to have structural, virulent and protective roles. Thus, elucidation of matrix components, their function and modulation by host environment is crucial to disclose their role in C. glabrata pathogenesis. As a major step toward this end, this study aimed to reveal, for the first time, the matrix proteome of C. glabrata biofilms, to characterize it with bioinformatic tools and to study its modulation by the environmental pH (acidic and neutral). The results showed the presence of several pH-specific matrix proteins (51 acidic- and 206 neutral-specific) and also proteins commonly found at both pH conditions (236). Of note, several proteins related to β-glucan metabolism, which have a potential role in the delivery/organization of matrix glucans, were found in both conditions but in much higher quantity under the neutral environment. Additionally, proteins with roles in adhesion, including epithelial adhesins, and virulence-related, including yapsins, were found among pH-specific and non-specific matrix proteins. Importantly, several proteins seem to have a non-canonical secretion pathway and Pdr1 was found to be a potential regulator of matrix proteome. Overall, this study indicates a relevant impact of environmental cues in the matrix proteome and provides a unique resource for further functional investigation of matrix proteins, contributing to the identification of potential targets for the development of new therapies against C. glabrata biofilms.
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