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.
Project description:Organisms adapt to and survive in environments with varying nutrient availability. Cis-regulatory changes play important roles in adaptation and phenotypic evolution. To what extent cis-regulatory elements contribute to metabolic adaptation is less understood. Here we have utilized a unique vertebrate model, Astyanax mexicanus, that survives in nutrient rich surface and nutrient deprived cave water to uncover gene regulatory networks in metabolic adaptation. We performed genome-wide analysis of accessible chromatin and histone modifications in the liver tissue of one surface and two independently derived cave populations, providing the first genome-wide epigenetic landscape in this organism. We find that many cis-regulatory elements differ between surface and the cavefish, while the two independently derived cave populations have evolved remarkably similar regulatory signatures. Changes in gene regulatory networks between the surface and cave morphotypes point to global changes in key metabolic pathways.
Project description:Organisms adapt to and survive in environments with varying nutrient availability. Cis-regulatory changes play important roles in adaptation and phenotypic evolution. To what extent cis-regulatory elements contribute to metabolic adaptation is less understood. Here we have utilized a unique vertebrate model, Astyanax mexicanus, that survives in nutrient rich surface and nutrient deprived cave water to uncover gene regulatory networks in metabolic adaptation. We performed genome-wide analysis of accessible chromatin and histone modifications in the liver tissue of one surface and two independently derived cave populations, providing the first genome-wide epigenetic landscape in this organism. We find that many cis-regulatory elements differ between surface and the cavefish, while the two independently derived cave populations have evolved remarkably similar regulatory signatures. Changes in gene regulatory networks between the surface and cave morphotypes point to global changes in key metabolic pathways.
Project description:we report a transcriptome-wide comparative investigation between surface and cave species in Sinocyclocheilus. De novo transcriptome assemblies were performed on surface and cave species; then the Sinocyclocheilus contigs were annotated with Gene Ontology. RNA-Seq assays revealed reduced transcription of a series of visual phototransduction and retinal disease related genes in cave-dwelling species compared with surface species. Degeneration of the retina in Sinocyclocheilus cavefish might occur in a lens-independent way by the down-regulation of several transcriptional factors, which have direct roles in retina development and maintenance, such as crx, rorb and Wnt pathway members. Examination of 2 different eye samples in 2 Sinocyclocheilus species.
Project description:The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.