A correlative study of the genomic underpinning of virulence traits and drug tolerance of Candida auris.

Candida auris is an opportunistic fungal pathogen with high mortality rates which presents a clear threat to public health. The risk of C. auris infection is high because it can colonize the body, resist antifungal treatment, and evade the immune system. The genetic mechanisms for these traits are not well known. Identifying them could lead to new targets for new treatments. To this end, we present an analysis of the genetics and gene expression patterns of C. auris carbon metabolism, drug resistance, and macrophage interaction. We chose to study two C. auris isolates simultaneously, one drug sensitive (B11220 from Clade II) and one drug resistant (B11221 from Clade III). Comparing the genomes, we confirm the previously reported finding that B11220 was missing a 12.8 kb region on chromosome VI. This region contains a gene cluster encoding proteins related to alternative sugar utilization. We show that B11221, which has the gene cluster, readily assimilates and utilizes D-galactose and L-rhamnose as compared to B11220, which harbors the deletion. B11221 exhibits increased adherence and drug resistance compared to B11220 when grown in these sugars. Transcriptomic analysis of both isolates grown on glucose or galactose showed that the gene cluster was upregulated when grown on D-galactose. These findings reinforce growing evidence of a link between metabolism and drug tolerance. B11221 resists phagocytosis by macrophages and exhibits decreased ß-1,3-glucan exposure, a key determinant that allows Candida to evade the host immune system, as compared to B11220. In a transcriptomic analysis of both isolates co-cultured with macrophages, we find upregulation of genes associated with transport and transcription factors in B11221. Our studies show a positive correlation between membrane composition and immune evasion, alternate sugar utilization, and drug tolerance in C. auris.

Mosquito sex and mycobiota contribute to fructose metabolism in the Asian tiger mosquito Aedes albopictus.

BACKGROUND: Plant floral nectars contain natural sugars such as fructose, which are a primary energy resource for adult mosquitoes. Despite the importance of carbohydrates for mosquito metabolism, a limited knowledge is available about the pathways involved in sugar assimilation by mosquitoes and their associated microbiota. To this end, we used 13C-metabolomic and stable isotope probing approaches coupled to high-throughput sequencing to reveal fructose-related mosquito metabolic pathways and the dynamics of the active gut microbiota following fructose ingestion. RESULTS: Our results revealed significant differences in metabolic pathways between males and females, highlighting different modes of central carbon metabolism regulation. Competitive and synergistic interactions of diverse fungal taxa were identified within the active mycobiota following fructose ingestion. In addition, we identified potential cross-feeding interactions between this. Interestingly, there is a strong correlation between several active fungal taxa and the presence of fructose-derived metabolites. CONCLUSIONS: Altogether, our results provide novel insights into mosquito carbohydrate metabolism and demonstrate that dietary fructose as it relates to mosquito sex is an important determinant of mosquito metabolism; our results also further highlight the key role of active mycobiota interactions in regulating the process of fructose assimilation in mosquitoes. This study opens new avenues for future research on mosquito-microbiota trophic interactions related to plant nectar-derived sugars. Video abstract.

A glutamic acid-producing lactic acid bacteria isolated from Malaysian fermented foods.

l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound.