Candida albicans is an opportunistic human pathogen which represents a significant threat to human health and is associated with substantial socio-economic burden. Current antifungal treatments fail at least in part because C. albicans can initiate a strong drug tolerance response, allowing cells to grow at concentrations above their minimal inhibitory concentration. Our goal is to better characterize this cytoprotective tolerance program at the molecular single cell level. We present here a nano-liter droplet-based fungal single cell transcriptomics platform capable of profiling thousands of individual C. albicans SC5314 cells in an efficient manner. Profiles of untreated cells partition into three transcriptional clusters with each highlighting a cell cycle checkpoint coupled with specific metabolic and stress responses, as perhaps expected. After just two days post-treatment with fluconazole, surviving cells bifurcate into two distinct subpopulations: the so-called α response involving upregulation of protein translation, rRNA processing and mitochondrial cellular respiration, and the β response involving processes and stress responses that assist damaged cells. By extending our time series to six days and profiling with other antifungals and bioactive compounds, we provide evidence that surviving cells transition from the α to β responses mediated by the Ribosome Assembly Stress Response (RASTR).

The fungus Candida albicans can “shape shift” between 12 morphologies in response to environmental variables. The cytoprotective capacity provided by this polymorphism makes C. albicans a formidable pathogen to treat clinically.

We study the microbiome of sea water collected from two locations of the Barbadian coral reefs. The two sites differ in several environmental and ecological variables including their endogenous benthic community and their proximity to urban development and runoffs from inland watersheds. The composition of the microbial communities was estimated using whole genome DNA shotgun sequencing with adjuvant measurements of chemical and environmental qualities. Although both sites exhibit a similar degree of richness, the less urbanized site (Maycocks reef at Hangman’s Bay) has a strong concentration of phototrophs whereas the more urbanized location (Bellairs reef at Folkstone) is enriched for copiotrophs, macroalgal symbionts and marine-related disease-bearing organisms from taxa scattered across the tree of life. Our results are concordant with previous profiles of warm ocean surface waters, suggesting our approach captures the state of each coral reef site, setting the stage for longitudinal studies of marine microbiome dynamics in Barbados.

We present deep learning-based approaches for exploring the complex array of morphologies exhibited by the opportunistic human pathogen C. albicans. Our system entitled Candescence automatically detects C. albicans cells from Differential Image Contrast microscopy, and labels each detected cell with one of nine vegetative, mating-competent or filamentous morphologies. The software is based upon a fully convolutional one-stage object detector and exploits a novel cumulative curriculum-based learning strategy that stratifies our images by difficulty from simple vegetative forms to more complex filamentous architectures. Candescence achieves very good performance on this difficult learning set which has substantial intermixing between the predicted classes. To capture the essence of each C. albicans morphology, we develop models using generative adversarial networks and identify subcomponents of the latent space which control technical variables, developmental trajectories or morphological switches. We envision Candescence as a community meeting point for quantitative explorations of C. albicans morphology.

We study the microbiome of sea water collected from two locations of the Barbadian coral reefs. The two sites differ in several environmental and ecological variables including their endogenous benthic community in addition to their proximity to urban development and runoffs from inland watersheds. The composition of the microbial community was estimated using whole genome DNA shotgun sequencing. Although both sites exhibit a similar degree of richness, the less urbanized site (Maycocks reef at Hangman’s Bay) is strongly concentrated with phototrophs. In comparison, the more urbanized location (Bellairs Research Institute) is enriched for copiotrophs, macroalgal symbionts and marine-related disease-bearing organisms from taxa scattered across the tree of life. Overall, our samples and associated measurements of chemical and environmental qualities of the water are in line with previous marine microbiome profiles of warm ocean surface waters. This suggests our approach captures salient information regarding the state of each coral reef site and sets the stage for larger longitudinal studies of coral reef dynamics in Barbados.