Transcriptomic analysis of chemotherapy-associated oropharyngeal candidiasis reveals a novel role of indigenous mucosal bacteria in pathogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE297794 | GEO | 2025/12/30
REPOSITORIES: GEO
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Project description:Oropharyngeal candidiasis (OPC) is the most prevalent oral infection in immunocompromised patients, primarily associated with Candida albicans. Increasing evidence points to a significant role of mucosal bacteria on the transition of C. albicans from commensal to pathogenic. In this work, we hypothesized that changes in the abundance or composition of the mucosal bacterial microbiota induced by dietary sucrose during the development of OPC can modulate C. albicans virulence. C. albicans burdens and mucosal lesions were evaluated in a mouse cortisone immunosuppression model amended with sucrose. We also analyzed the mucosal bacterial composition using 16S rRNA gene sequencing and culture methods. In immunocompetent mice, sucrose significantly increased total bacterial burdens and reduced alpha diversity, by increasing the relative abundance of mitis group streptococci. In immunocompromised mice, C. albicans infection was associated with a significantly reduced bacterial alpha diversity due to an increase in the relative abundance of enterococci. When exposed to dietary sucrose, these mice had reduced C. albicans burdens and reduced bacterial alpha diversity, associated with an increase in the relative abundance of Lactobacillus. SparCC correlation networks showed a significant negative correlation between Lactobacillus and Enterococcus in all Candida-infected mice. Depletion of lactobacilli with antibiotic treatment partially restored C. albicans burdens in mice receiving sucrose. In coculture in vitro experiments, mouse oral Lactobacillus johnsonii isolates inhibited growth of Enterococcus faecalis isolates and C. albicans. These results support the hypothesis that the sucrose-induced attenuation of C. albicans virulence was a result of changes in the mucosal bacterial microbiome characterized by a reduction in enterococci and an increase in lactobacilli. IMPORTANCE By comparing Candida albicans virulence and the mucosal bacterial composition in a mouse oral infection model, we were able to dissect the effects of the host environment (immunosuppression), infection with C. albicans, and local modulating factors (availability of sucrose as a carbon source) on the mucosal bacterial microbiome and its role on fungal virulence. We showed that changes in endogenous microbial communities in response to sucrose can lead to attenuation of fungal disease. We also showed that Lactobacillus johnsonii may curtail Candida virulence both by inhibiting its growth and by inhibiting the growth of potentially synergistic bacteria such as enterococci. Our results support the concept that Candida pathogenesis should be viewed in the contexts of both a susceptible host and a mucosal bacterial microbiota conducive to virulence.
| S-EPMC8406182 | biostudies-literature
Project description:Transcriptomic analysis of chemotherapy-associated oropharyngeal candidiasis reveals a novel role of indigenous mucosal bacteria in pathogenesis
| PRJNA1266194 | ENA
Project description:Transcriptional profiling of C. albicans when monocultured in suspension culture or in biofilms compared to when co-cultured with C. perfringens in suspension culture, or with E. coli, K. pneumoniae, E. faecalis, C. perfringens, or B. fragilis in biofilms, or in the presence of N-acetylglucosamine in biofilms.
2014-03-03 | GSE55026 | GEO
Project description:Transcriptional profiling of C. albicans when monocultured in suspension culture or in biofilms compared to when co-cultured with C. perfringens in suspension culture, or with E. coli, K. pneumoniae, E. faecalis, C. perfringens, or B. fragilis in biofilms, or in the presence of N-acetylglucosamine in biofilms. At least 2 replicates for each condition except for biofilms +N-acetylglucosamine, some experiments are two-condition experiments: C. albicans +/- bacteria vs. C. albicans. Some experiments multiple condition: C. albicans +/- bacteria vs. mixed reference of all conditions in that experiment.
2014-03-03 | E-GEOD-55026 | biostudies-arrayexpress
Project description:Candida albicans, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron-limitation using Deferasirox (an FDA approved iron chelator for treatment of patients with iron overload) during murine OPC; and assessed Deferasirox-treated C. albicans for its interaction with human oral epithelial (OE), neutrophils, and antimicrobial peptides. Therapeutic Deferasirox treatment significantly reduced salivary iron levels while a non-significant reduction in fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model, resulted in significant reduction of C. albicans colony forming units (CFU)/g of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans harvested from tongues of animals undergoing preventive treatment had differential expression of 106 genes, including those involved in iron metabolism, adhesion, and response to host innate immunity. Moreover, Deferasirox-treated C. albicans cells had two-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress); and reduced adhesion and invasion of OE cells, in vitro. Thus Deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence
2018-12-04 | GSE123277 | GEO
Project description:IL17A KO mouse tongues after 2 days of C. albicans infection were profiled and compared to WT. In addition, tongues from animals infected for 2 days with C. albicans and then treated with anti-IL17A antibody, anti-IL17F antibody, anti-IL17A and anti-IL17F antibodies together, or isotypes controls were analyzed.
2015-12-21 | E-MTAB-4167 | biostudies-arrayexpress
Project description:We sought to identify transcriptomic changes that arise when E. faecalis biofilms are cultivated in the presence of C. albicans. We used RNASeq analaysis to compare the transcriptome of 48 hr biofilm-grown cells of E. faecalis. We compared the transcriptome of E. faecalis cells grown as a mono-species biofilm to that of E. faecalis cells that were grown in a biofilm that was co-inoculated with the yeast C. albicans.
2025-03-03 | GSE290415 | GEO
Project description:Candida albicans metamorphoses from benign yeast to a rigid hyphae , becoming an opportunistic pathogen in immunocompromised patients. The process by which immune cells discern fungal transformations remains elusive. Here we report that the mechanosensitive ion channel Piezo1 is indispensable for recognizing fungal hyphae and triggering anti-fungal innate immune responses. Hyphae-triggered Piezo1 activation increased CLRs expression in innate immune cells by inducing the expression of C/EBPb via the Piezo1/CaMKs/CREB axis. In addition, Piezo1/CaMKs signaling activated kinases NDR1/2, which augmented NLRP3 inflammasome assembly and promoted hyphae-induced inflammation. Abolishing the yeast-to-hyphae transition dampens CLR and NLRP3 activation. Piezo1-deficient mice exhibit compromised clearance of C. albicans infection, whereas Piezo1 agonist amplifies C. albicans clearance. In addition, CaMKs, CREB or NDR1/2 inhibition exacerbates hyphae infections, like Piezo1 deficiency. Therefore, we ascertain Piezo1-mediated mechanotransduction as vital for immune surveillance and control of hyphal C. albicans, heralding Piezo1 agonist as a potential remedy for fungal infections.
2025-05-21 | GSE293094 | GEO
Project description:Candida albicans metamorphoses from benign yeast to a rigid hyphae , becoming an opportunistic pathogen in immunocompromised patients. The process by which immune cells discern fungal transformations remains elusive. Here we report that the mechanosensitive ion channel Piezo1 is indispensable for recognizing fungal hyphae and triggering anti-fungal innate immune responses. Hyphae-triggered Piezo1 activation increased CLRs expression in innate immune cells by inducing the expression of C/EBPb via the Piezo1/CaMKs/CREB axis. In addition, Piezo1/CaMKs signaling activated kinases NDR1/2, which augmented NLRP3 inflammasome assembly and promoted hyphae-induced inflammation. Abolishing the yeast-to-hyphae transition dampens CLR and NLRP3 activation. Piezo1-deficient mice exhibit compromised clearance of C. albicans infection, whereas Piezo1 agonist amplifies C. albicans clearance. In addition, CaMKs, CREB or NDR1/2 inhibition exacerbates hyphae infections, like Piezo1 deficiency. Therefore, we ascertain Piezo1-mediated mechanotransduction as vital for immune surveillance and control of hyphal C. albicans, heralding Piezo1 agonist as a potential remedy for fungal infections.
2025-05-22 | GSE279850 | GEO
Project description:The fungal species Candida albicans and the bacterium Enterococcus faecalis are both common members of the gut microbiome, with co-occurrence of these two species widely reported in dysbiotic gut environments. While prior research suggests these species interact in the gut, the underlying mechanisms of these interactions remain unclear. To explore these interactions further, we utilized dual RNA-sequencing to transcriptionally profile both C. albicans and E. faecalis during co-culture and mono-culture under two conditions: (1) an in vitro condition designed to mimic certain aspects of the gut environment and (2) the germ-free mouse gut. Gene expression analysis revealed that both species strongly upregulate citrate-related genes during co-culture: C. albicans upregulates CIT1 (citrate synthase) which produces citrate, while E. faecalis upregulates its cit operon, responsible for citrate metabolism. In vitro co-cultures revealed that citrate cross-feeding supports increased growth of E. faecalis, which depends both on C. albicans' expression of CIT1 and E. faecalis' expression of the cit operon. A main byproduct of citrate metabolism in E. faecalis is formate, a short chain fatty acid (SCFA) toxic to fungi. Our RNA profiling revealed that C. albicans strongly upregulates three formate dehydrogenases (FDHs) during co-culture, enabling formate detoxification and conferring a growth advantage to C. albicans when grown in E. faecalis conditioned medium. These findings reveal a metabolically driven interaction between C. albicans and E. faecalis in the gut, where cross-feeding of citrate and detoxification of formate facilitates the growth of both species when they are cultured together. Using a simplified fungal-bacterial co-culture system, our studies begin to reveal the mechanistic complexities of metabolic sharing between a eukaryote and a bacterium.
2025-08-11 | GSE288745 | GEO