Project description:Amino sugars, particularly glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) are abundant carbon and nitrogen sources that are continually supplied in host secretions and the diet to biofilms colonizing the human mouth. Evidence is emerging that these amino sugars may provide an ecological advantage to beneficial commensals over oral pathobionts. Here we performed transcriptome analysis on Streptococcus mutans and Streptococcus gordonii growing in single-species or dual-species cultures with glucose, GlcN or GlcNAc as the primary carbohydrate source. Compared to glucose, GlcN caused drastic transcriptomic shifts in each bacterium when they were cultured alone. Likewise, co-cultivation in the presence of GlcN yielded transcriptomic profiles that were dramatically different than the single-species results from GlcN-grown cells. In contrast, GlcNAc elicited only minor changes in the transcriptome of either organism, in both single- and dual-species cultures. Interestingly, genes involved in pyruvate metabolism were among the most significantly affected by GlcN in both species, and these changes were consistent with measurements of pyruvate in culture supernates. Differing a previous report, growth of S. mutans alone with GlcN inhibited expression of multiple operons required for mutacin production. Co-cultivation with S. gordonii consistently increased the expression by S. mutans of two manganese transporter operons (slo and mntH) and decreased expression of mutacin genes. Conversely, S. gordonii appeared to be less affected by the presence of S. mutans, but did show increases in genes for biosynthetic processes in the co-cultures. In conclusion, amino sugars profoundly altered the interactions between the pathogen and the commensal, likely by reprogramming their central metabolism.
Project description:Healthcare providers are routinely being assessed for metrics designed to assess the quality of the care they deliver. There is growing consensus that these measurements, which typically assess the percentage of patients meeting a specific standard of care, should be adjusted for the clinical complexity of the providers. This study will assess whether adjusting for the social complexity of the patient panel adds significantly to adjustment for clinical complexity in explaining apparent differences in quality of care provided by Primary care providers and clinics.
Project description:Efficient utilization of lignocellulosic biomass-derived sugars is essential to improve the economics of biorefinery. While Pseudomonas putida is a promising microbial host, its usage is limited because this strain cannot utilize xylose or galactose as a sole carbon source. To address this issue, we heterologously introduced a xylose utilizing gene (xylD) from Caulobacter crescentus and a galactose operon (galETKM) from E. coli MG1655. To improve the utilization further, we evolved the engineered strains in minimal medium conditions. After the evolution, they acquired better fitnesses on the non-native sugars. To understand transcriptional changes after the evolution, the transcriptomes of few evolved isolates were analyzed.
Project description:The purpose of this study was to characterize carbon metabolism and gene regulation in Alicyclobacillus acidocaldarius during growth on wheat arabinoxylan and the effect of pentose and hexose sugars on gene expression Chemostat studies and global transcriptome analysis were used to accomplish this goal.
Project description:Yeast sugar transporters are highly evolved for optimized glucose transport, a major roadblock when it comes to utilizing non-glucose sugars in renewable feedstocks such as lignocellulosic biomass. The AtSWEET7p transporter has been identified for simultaneous transport of glucose and xylose, prevalent in plant cell wall hydrolysates. Here, we replaced endogenous hexose transporters with AtSWEET7 to construct an engineered Saccharomyces cerevisiae capable of multiple sugars with no glucose repression. The resulting strain (NKSW7-1) gained the capacity to simultaneously co-ferment glucose, xylose, mannose, and fructose in a synthetic medium, as well as the sugars in mixtures of bagasse hydrolysate and cane juice. Notably, the replacement of native sugar transporters by AtSWEET7 led to reprogramming of central carbon metabolism, activating glucose-repressed genes even in the presence of substantial amounts of glucose. Continuous culture experiments with the NKSW7-1 strain demonstrated feasibility of AtSWEET7 to disable glucose repression on other hexose or/and pentose sugar uptake. The broad transport capacity of AtSWEET7p can be utilized for achieving co-consumption of all sugars, especially in the case of emerging, underutilized, and renewable substrates.