Abstract
Candida glabrata is a clinically relevant human pathogen with the 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 the 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 mannan and β-glucan metabolism, which have a potential role in the delivery/organization of carbohydrates in the matrix, were found in both pH conditions but in much higher quantity under the neutral environment. Additionally, several virulence-related proteins, including epithelial adhesins, yapsins and moonlighting enzymes, were found among 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.
Highlights
Candida species are opportunistic human pathogens capable of causing a broad range of infections [1,2,3]
Candida albicans is the main cause of candidiasis, recent epidemiologic surveys have pointed to an increase in infections caused by non-Candida albicans Candida species, mainly Candida glabrata [1,2]
The comparison with C. albicans revealed that 339 proteins found in this study are orthologs of proteins previously found in the matrix of C. albicans biofilms (Table 1 and Supplementary Table S1) [19,27,28]
Summary
Candida species are opportunistic human pathogens capable of causing a broad range of infections [1,2,3]. Candida albicans is the main cause of candidiasis, recent epidemiologic surveys have pointed to an increase in infections caused by non-Candida albicans Candida species, mainly Candida glabrata [1,2]. C. glabrata causes complicated infections that range from agonizing episodes of vulvovaginal candidiasis to life-threatening candidemia and that are associated with high morbidity and mortality (∼50%) rates [1,2,4]. The high clinical relevance of C. glabrata infections, is mainly attributed to the intrinsic and acquired antifungal resistance of this species [5,6], as well as to its ability to display several virulence factors, one of the most important is the ability to form biofilms on mucosae and medical devices [7,8]. Biofilm-related infections caused by C. glabrata are extremely difficult to treat due to the high resilience of its biofilms to antifungals and host defences [10,11]
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