metabolism
Research Article | Molecular Biology and PhysiologyPlasmodium falciparum Apicomplexan-Specific Glucosamine-6-Phosphate N-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage DevelopmentApicomplexan parasites cause a major burden on global health and economy. The absence of treatments, the emergence of resistances against available therapies, and the parasite’s ability to manipulate host cells and evade immune systems highlight the urgent need to characterize new drug targets to treat infections caused by these parasites. We demonstrate that glucosamine-6-phosphate N-acetyltransferase (GNA1), required for the...
Research Article | Host-Microbe BiologyInvertases in Phytophthora infestans Localize to Haustoria and Are Programmed for Infection-Specific ExpressionOomycetes cause hundreds of diseases in economically and environmentally significant plants. How these microbes acquire host nutrients is not well understood. Many oomycetes insert specialized hyphae called haustoria into plant cells, but unlike their fungal counterparts, a role in nutrition has remained unproven. The discovery that Phytophthora invertases localize to haustoria provides the first strong evidence that these...
Research Article | Host-Microbe BiologyImpact of Facultative Bacteria on the Metabolic Function of an Obligate Insect-Bacterial SymbiosisAlthough microbial colonization of the internal tissues of animals generally causes septicemia and death, various animals are persistently associated with benign or beneficial microorganisms in their blood or internal organs. The metabolic consequences of these persistent associations for the animal host are largely unknown. Our research on the facultative bacterium Hamiltonella, localized primarily to the hemolymph of pea...
Research Article | Molecular Biology and PhysiologyExpression of the Long Noncoding RNA DINO in Human Papillomavirus-Positive Cervical Cancer Cells Reactivates the Dormant TP53 Tumor Suppressor through ATM/CHK2 SignalingFunctional restoration of the TP53 tumor suppressor holds great promise for anticancer therapy. Current strategies are focused on modulating TP53 regulatory proteins. Long noncoding RNAs (lncRNAs) have emerged as important regulators of TP53 as well as modulators of downstream tumor-suppressive transcriptional responses. Unlike many other cancer types, human papillomavirus (HPV)-positive cancer cells retain wild-type TP53 that is...
Research Article | Host-Microbe BiologyMultiple Alternative Carbon Pathways Combine To Promote Candida albicans Stress Resistance, Immune Interactions, and VirulenceCandida albicans is a fungal pathogen and a significant cause of morbidity and mortality, particularly in people with defects, sometimes minor ones, in innate immunity. The phagocytes of the innate immune system, particularly macrophages and neutrophils, generally restrict this organism to its normal commensal niches, but...
Research Article | Host-Microbe BiologyThe Metabolite Repair Enzyme Phosphoglycolate Phosphatase Regulates Central Carbon Metabolism and Fosmidomycin Sensitivity in Plasmodium falciparumThe malaria parasite has a voracious appetite, requiring large amounts of glucose and nutrients for its rapid growth and proliferation inside human red blood cells. The host cell is resource rich, but this is a double-edged sword; nutrient excess can lead to undesirable metabolic reactions and harmful by-products. Here, we demonstrate that the parasite possesses a metabolite repair enzyme (PGP) that suppresses harmful metabolic by-...
Research Article | Molecular Biology and PhysiologyStochastic Variation in Expression of the Tricarboxylic Acid Cycle Produces Persister CellsPersister cells are rare phenotypic variants that are able to survive antibiotic treatment. Unlike resistant bacteria, which have specific mechanisms to prevent antibiotics from binding to their targets, persisters evade antibiotic killing by entering a tolerant nongrowing state. Persisters have been implicated in chronic infections in multiple species, and growing evidence suggests that persister cells are responsible for many cases of...
Research Article | Molecular Biology and PhysiologyThe TK0271 Protein Activates Transcription of Aromatic Amino Acid Biosynthesis Genes in the Hyperthermophilic Archaeon Thermococcus kodakarensisThe mechanisms of transcriptional regulation in archaea are still poorly understood. In this study, we identified a transcriptional regulator in the hyperthermophilic archaeon Thermococcus kodakarensis that activates the transcription of three operons involved in the biosynthesis of aromatic amino acids. The study represents one of only a few that identifies a...
Research Article | Ecological and Evolutionary ScienceSystems Biology and Pangenome of Salmonella O-AntigensLipopolysaccharides are a major component of the outer membrane in Gram-negative bacteria. They are composed of a conserved lipid structure that is embedded in the outer leaflet of the outer membrane and a polysaccharide known as the O-antigen. O-antigens are highly variable in structure across strains of a species and are crucial to a bacterium’s interactions with its environment. They constitute the first line of defense against both...
Research Article | Molecular Biology and PhysiologyIdentification of Dephospho-Coenzyme A (Dephospho-CoA) Kinase in Thermococcus kodakarensis and Elucidation of the Entire CoA Biosynthesis Pathway in ArchaeaCoA is utilized in a wide range of metabolic pathways, and its biosynthesis is essential for all life. Pathways for CoA biosynthesis in bacteria and eukaryotes have been established. In archaea, however, the enzyme that catalyzes the final step in CoA biosynthesis, dephospho-CoA kinase (DPCK), had not been identified. In the present study, bioinformatic analyses identified a candidate for the DPCK in archaea, which was biochemically and...